Pharm Infectious Disease

Piperacillin and tazobactam(Zosyn)

Beta-Lactamase Inhibitor Clinical Uses: Covers many gram positive, gram negative, and anaerobes Piperacillin and tazobactam(Zosyn): about as broad as you can get Human and animal bites Aspiration pneumonia Foot infections in diabetic patients Sinusitis Resistant otitis media Lung abscess Does not cover MRSA No major adverse events w/ beta-lactamase inhibitors such as tazobactam Hypersensitivity reactions and GI side effects (oral admin) Elevated liver function (not common) Drug interactions: do not combine with parenteral aminoglycosides (inactivation with aminogycosides in vitro)

Cephalosporins

Beta-Lactams Pharmacodynamics: structurally and chemically similar to PCNs Inhibit mucopeptide synthesis in the bacterial cell wall. Bactericidal Four generations First generation: Cefazolin (Ancef), Cephalexin (Keflex), Cefadroxil Used for gram positive skin and soft tissue infections Primarily active against gram-positive bacteria, S. aureus and S. epidermidis Second generation: Cefuroxime (Ceftin), Cefaclor Active against same as first generation, plus Klebsiella, Proteus, E. coli Third generation: Ceftriaxone, Cefotaxime, Ceftazidime Used for broader indications More active against gram-negative bacteria; Does not cover MRSA; Treats community acquired bacterial meningitis Fourth generation: Cefepime (Maxipime) Resistant to beta-lactamase Primarily active against gram-positive bacteria Progression from 1st to 4th reflects an increase in gram - coverage and loss of gram + cover. There is a fifth generation of cephalosporins: The 5th-generation cephalosporin ceftaroline given IV & is active against Methicillin-resistant S. aureus (MRSA) and E. faecalis. Its activity against other gram-positive cocci and gram-negative bacilli is similar to that of 3rd-generation cephalosporins. It is not active against Pseudomonas sp. All cephalosporins penetrate poorly into ICF and the vitreous humor. Pharmacokinetics: Oral formulations absorbed from GI tract Widely distributed to most tissues Some highly bound to proteins Some are metabolized to less active compounds, most excreted via kidneys, in various degrees as unchanged drug ADRs: allergies, skin rashes, arthralgia, coagulation abnormalities, anemia, neutropenia, leukopenia, thrombocytosis, fever, seizures, renal/hepatic failure Hypersensitivity reaction Maculopapular rash and urticaria Cross-reaction with penicillin 3 to 10% Can have GI effects transient Drug interaction: Probenicid can increase the half-life *Clinical use and dosing Used for therapeutic failure in AOM First generation: strep pharyngitis, skin infections Cephalexin, cefpodoxime, cefixime can be prescribed as second-line drugs for urinary tract infection (UTI). Ceftriaxone and cefixime used for general condition gonococcus (GC)/chlamydia Cefpodoxime, cefuroxime, or parenteral ceftriaxone followed by oral cefpodoxime are used for community-acquired pneumonia. Most cephalosporins are pregnancy category B Monitoring For diarrhea (C. difficile) Renal function, if prolonged therapy Patient education Use as prescribed. Educate potential adverse drug reactions. Since there are so many meds which belong to the Cephalosporin class, there are multiple indications for use. In general know particularly the meds mentioned in this slide. UTI treatment-Cephalexin, cefpodoxime, cefixime are SECOND-line drugs for UTI. However, they're not preferred Rx. Cephtriaxone 250 mg. IM x1 is still the preferred out-patient treatment for gonorrhea. Pt sould be rechecked in 3-6 months for gonorrhea/chlamydia. But, cefixime can be used as a po alternative per 2015 CDC guidelines. Please be sure to check the pregnancy guidelines before ordering. They MUST complete the ABX course as prescribed. Skin infections can be caused by bacteria, virus, fungus, or parasites. Cellulitis is an infection of the dermis and subcutaneous tissue that has poorly demarcated borders and is usually caused by Streptococcus or Staphylococcus species. Impetigo is also caused by Streptococcus or Staphylococcus. Folliculitis is an inflammation of the hair follicles & when the infection is bacterial rather than mechanical in nature, it is most commonly caused by Staphylococcus. If antibiotics are required, one that is active against gram-positive organisms such as penicillinase-resistant penicillins, cephalosporins, macrolides, or fluoroquinolones should be chosen.

Penicillin

Beta-lactam Pharmacodynamics Inhibit the biosynthesis of peptidoglycan bacterial cell wall Sensitivity -Natural penicillins: Streptococcus, some Enterococcus strains, some non-penicillinase-producing Staphlococcus -Aminopenicillins greater activity against gram-negative bacteria due to enhanced ability to penetrate the outer membrane organisms -Used for gram-negative urinary and gastrointestinal (GI) pathogens E. coli, Proteus mirabilis, Salmonella, some Shigella species, and Enterococcus faecalis; active against the common gram-negative respiratory pathogens Moraxella catarrhalis (and Haemophilus influenzae type B) Combination with beta-lactamase inhibitors to broaden their spectrum: clavulanate, sulbactam, tazobactam Amoxicillin and clavulanate (Augmentin) combination is an antibiotic that belongs to the group of medicines known as penicillins and beta-lactamase inhibitors. It works by killing the bacteria and preventing their growth. Aminopenicillins have a broader spectrum Pharmacokinetics Well-absorbed from GI tract, but several are unstable in acid: dicloxacillin and amoxicillin better absorbed than ampicillin Bound to proteins with good distribution to most tissues Small amount is metabolized, most excreted as unchanged drug in the urine. Probenecid prolongs the half-life and increases risk for toxicity. Because PCNs are bound to proteins they have good distribution throughout most tissues Small amount is metabolized, most excreted as unchanged drug in the urine. So, pay close attention to kidney function Clinical use and dosing Commonly prescribed for infections seen in primary care Amoxicillin is first-line therapy for acute otitis media (AOM), pharyngitis, and sinusitis. Penicillin (PCN) is used for streptococcal pharyngitis & syphilis. Amoxicillin/clavulanate is first-line therapy for infection following bites, including human. Rational drug selection Defining tests (rapid strep) vs. empiric method Cost Amoxicillin is top ABX prescribed to children and 2nd most prescribed ABX for adults. If a patient has a failed amoxicillin course and the infection does not resolve or recurs within a few weeks, you would then order Amoxicillin-clavulanate (to add the beta-lactamse inhibitor). The American Academy of Pediatrics (AAP) released revised clinical practice guidelines for the diagnosis and management of uncomplicated AOM in children aged 6 months through 12 years in 2013. The updated recommendations, intended as a clinical decision-making framework for primary care physicians (PCPs), provide more rigorous diagnostic criteria intended to decrease unnecessary antibiotic use, as well as address therapeutic options, analgesia, prevention, and appropriate selection of antibiotics. They also discuss recurrent AOMAntibiotics are the only medications with demonstrated efficacy in the management of AOM once the diagnosis is confirmed. Amoxicillin is the antibiotic of choice unless the child received it within the previous 30 days, has concurrent purulent conjunctivitis, or is allergic to penicillin; in these cases, clinicians should prescribe an antibiotic with additional β-lactamase coverage. Resource: http://emedicine.medscape.com/article/859316-guidelines Research has shown ABX do have a modest effect on the disease because they shorten recovery by 1 day. The antibiotic chosen should cover most of the common bacterial pathogens and be individualized for the child with regard to allergy, tolerance, previous exposure to antibiotics, cost, and community resistance levels. Delayed ABX therapy is only recommended if child is > 6 months old or older and healthy w/ unilateral AOM. They must be rechecked to check progress. Other Uses: Pneumonia, STIs, UTI, and Wound Infections Endocarditis prophylaxis Helicobacter pylori Lyme Disease Because the common cold (URI) & acute bronchitis are seasonal, self-limiting illnesses usually caused by viruses, ABX do not have a role in treatment plan if it is an uncomplicated case. ABX Treatment is indicated prolonged cough with diagnosed etiology such as Bordetella pertussis or Mycoplasma pneumoniae. And penicillins are not usually drug of choice. Adverse drug reactions (ADRs) May cause serious immediate allergic reactions Reactions occur within 2 to 30 minutes of administration. Patients may be given desensitization therapy. Rash: maculopapular rash occurs 9% of time that is not allergic in origin, appears 7 to 10 days into treatment. GI: diarrhea, nausea/vomiting (n/v), addition of clavulanate increases risk of diarrhea Fungal overgrowth C. difficile colitis Most are pregnancy category B. Most are pregnancy category B, so if a pregnant woman develops a UTI, an appropriate ABX would be amoxicillin. It would also be wise to culture the urine before starting ABX in case it is not sensitive to that particular ABX The safety of a penicillin in a cephalosporin-allergic patient depends on whether the patient is truly allergic, when the reaction occurred, and the nature of the allergy (immediate or nonimmediate). In the past, we thought the cross-sensitivity was 10-205. Recent research (2012) tells us the overall cross reactivity between penicillins and cephalosporins in individuals who report a penicillin allergy is approximately 1 %, and in those with a confirmed penicillin allergy, 2.5%. For patients with a questionable history of penicillin allergy, skin testing predicts a true penicillin allergy but does not reliably predict allergy to cephalosporins. Monitoring Return to office for evaluation of symptom relief. Are symptoms getting better? Patient education: resistance, ADRs, completing course Hypersensitivity reactions: most common adverse reactions with penicillins. Penicillins are cross sensitizing and cross reacting. Anaphylactic shock Type I-most serious, urticaria, pruritus. -Type II: hemolytic anemia, neutropenia(nafcillin), thrombocytopenia. -Type III: Serum sickness (rare-urticaria, fever joint swelling, angioneuroticedema, pruritus, bronchospasm-7-12 days after), interstitial nephritis(methicillin). -Type IV: contact dermatitis.

Drugs that inhibit cell wall synthesis

Beta-lactams Penicillins (+/- Beta-lactamase inhibitors) Cephalosporins (3 generations) Monobactams Carbapenems Glycopeptides Fosfomycin

Chancroid and rational drug selection

Treatment is initiated when these criteria are satisfied One or more painful ulcers Negative tests for syphilis and HSV The appearance of ulcers with suppurative inguinal adenopathy Treatment Azithromycin: 1 gm by mouth one time, or Ceftriaxone: 250 mg IM, or Ciprofloxacin: 500 mg by mouth twice daily for 3 days, or Erythromycin: 500 mg by mouth three times/day for 7 days Patients are reexamined 3 to 7 days after therapy is started. Patients should have HIV testing. Sexual partners are examined and treated if they had sexual contact with patient in past 10 days. Chancroid ( human genital ulcer disease) is an STI caused by exposure to Haemophilus ducreyi. This is a small, gram-negative rod bacteria that occurs mainly in developing countries, especially in Africa, Asia and Latin America.

STIs: Patient Education

Treatment plan Reason for taking drugs Drug ADRs Partner treatment Follow-up testing

HIV Outcome Evaluation

Treatment plans are individualized to each patient. Success is determined by when the patient begins therapy and how well he or she is able to adhere to therapy.

Genital Herpes: Rational Drug Selection

Two serotypes of HSV: HSV-1 and HSV-2 50 million people have HSV infection. Suppressive antiviral therapy reduces but does not eliminate subclinical viral shedding. Treatment: Acyclovir, famciclovir, and valacyclovir are the mainstay of treatment for genital herpes. Treat partners.

Vaginitis: Rational Drug Selection, monitoring, outcome evaluation, pt education

Use correct drug for pathogen. Consider resistance. Cost Over-the-counter antifungals are inexpensive. Patient variables Pregnancy may affect treatment choices. Drug variables Intravaginal medications have the fewest drug interactions Monitoring No ongoing monitoring required unless chronic infection. Outcome evaluation If patient does not respond to therapy consider referral. Patient education Treatment plan Adherence issues

STI: Rational Drug Selection

Use current Centers for Disease Control (CDC) or Canada Health Guidelines. Updated frequently Extensive guidelines for all patient populations including pregnant women

STI Patho

Vaginal flora Disturbance of normal vaginal flora increases risk of contracting STI. Sex of patient: women more than men Number of sexual partners Immune system status Coexisting infections

Drugs that are antimetabolites

Sulfonamides

Trimethaprim/Sulfamethoxazole (Bactrim, Septra, TMP/SMZ)

Sulfonamides Mechanism of action: Anti-metabolite, folate antagonist Coverage: gram + and gram - Does not cover pseudomonas, anaerobes, or group A strep Silver Sulfadiazine (Silvadene): topical agent frequently used in treating burns TMP/SMZ : UTIs, MRSA, bronchitis, pneumocystis pneumonia Adverse events: rash, GI side effects most common; Hemolytic anemia can occur in patients with glucose-6-phosphate dehydrogenase deficiency Drug interactions: Potentiate the effects of warfarin, phenytoin, hypoglycemic agents, and methotrexate. Sulfonamides increase hypoglycemic effect of sulfonylureas; TMP/SMX may increase anticoagulant effect of warfarin; TMP/SMX given w/ cyclosporine increases kidney toxicity risk. Sulfonamide given w/ methenamine could lead to urinary crystals.

Stages of HIV

Symptomatic primary HIV infection approximately 2 to 4 weeks after infection Flu-like viral syndrome develops with fever, lymphadenopathy, pharyngitis, rash, and myalgias Asymptomatic infection No abnormal physical findings Symptomatic HIV infection Development of common infections Advanced HIV disease/AIDS Severe immunosuppression, CD4 T lymphocytes (CD4 cells) count less than 200 cells/mm3

Vaginitis: Goals of Treatment

Treat the infection or inflammation, prevent reinfection, and prevent complications of the infection or inflammation. Accurate diagnosis is essential for treatment. Phone diagnosis is not always accurate.

Gonorrhea & Chlamydia treatment

Treat with ceftriaxone 250 mg IM (or cefixime 400 mg po) and Azithromycin 1 gram po x1 or doxycycline 100 mg po BID x 7 days

Definitive therapy

antibiotic therapy tailored to treat organism identified with cultures

Empiric therapy

treatment of an infection before specific culture information has been reported or obtained

Prophylactic therapy:

treatment with antibiotics to prevent an infection, as in intraabdominal surgery or after trauma

Antimicrobial selection

1. Clinical diagnosis 2. Obtain cultures/specimens 3. Microbial diagnosis based on most likely organism or culture/test result 4. Select appropriate medication 5. May need to change drug based on culture/sensitivity test results

study-guide table naming mechanism of action for the variety of antiinfectives available to providers & patients

A Leptopeptide would be daptomycin (Cubicin) & it treats very complicated skin infections & staphylococcus aureus bacteremia, including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates. Polymyxin: With the emergence of multidrug resistant (MDR) gram-negative bacteria and the lack of development of new antimicrobial agents, we have the revival of polymyxins as "salvage" therapy for the treatment of nosocomial infections due to MDR Gram negative bacteria. Polymyxins should be considered for the treatment of infections caused by Gram negative bacteria resistant to other available antimicrobial agents, confirmed by appropriate in vitrosusceptibility testing. http://www.antimicrobe.org/d05.asp Colistin (polymyxin E) is being utilized in U.S. and fortunately, resistance to Colistin is still relatively uncommon

Antimicrobial / Antiinfective agent:

A general term for drugs, chemicals, or other substances that either kill or slow the growth of microbes. They can be antibacterial drugs, antiviral agents, antifungal agents, and antiparisitic drugs. would encompass antibacterial drugs, antiviral agents, antifungal agents, and antiparisitic drugs.

Antibiotic

A large group of chemical substances, such as penicillin or streptomycin, produced by various microorganisms and fungi, having the capacity in dilute solutions to inhibit the growth of or to destroy bacteria and other microorganisms, used chiefly in the treatment of infectious diseases. has the ability to destroy or interfere with the development of a living organism. The term is most frequently used in reference to antibacterial drugs.

Chlamydia and rational drug selection

All sexually active women under 25 years should be screened annually. All women with new or multiple sex partners need to be screened. Treatment: azithromycin 1 gm by mouth one time or doxycycline 100 mg twice daily for 7 days. Patient should also be treated for gonorrhea. Pregnant women: azithromycin 1 Gram po x1 and need test if cure and retesting in 3 months. Sexual partners in past 60 days should be tested. Chlamydia: Pathogen: intracellular gram-negative bacterium - C. Trachomatis Most common cause of non-gonococcal urethritis. Highest incidences less than 25 years of age. Sequelae: Pelvic inflammatory disease (PID); Ectopic pregnancy; Infertility Signs: beefy, red, friable cervix. Symptoms: watery urethral discharge. Causes epididymitis (males); PID (women). Culture for both chlamydia & gonorrhea Pregnant patients: Azithromycin 1 gram PO x 1 dose or Amoxicillin 1 g PO x 1 dose or Amoxicillin 500 mg PO TID x 7 days

Antivirals: Nucleoside Analogues. ADRs, Drug interactions, clinical use and dosing, rational drug selection, monitoring, pt education

ADRs Acyclovir/valacyclovir: few ADRs when given orally Valacyclovir may cause thrombocytopenia purpura, hemolytic uremic syndrome in immunocompromised patients. Famciclovir: headache Ganciclovir: granulocytopenia, anemia and thrombocytopenia; may be carcinogenic Elimination: -Renal-renal failure reported in all drugs of this class Drug interactions Few Clinical use and dosing Herpes simplex virus: genital herpes, both initial outbreak and suppression therapy Herpes zoster (shingles): Start therapy within 3 days of outbreak. Varicella (chickenpox): Start within 24 hours of outbreak. Gingivostomatitis in children Bell's palsy Rational drug selection Choice based on cost and convenience Acyclovir is the least expensive, but must keep in mind the 5x/day dosing. Will the patient take it as directed if it is dosed this frequently? Monitoring Rash/lesions for resolution Temperature Blood urea nitrogen and creatinine high-risk patients Acyclovir, valaciclovir and famciclovir-pregnancy category B Ganciclovir- pregnancy category C Patient education Drug started at earliest sign of infection Good hydration Educate regarding symptoms of renal failure, encephalopathic changes, blood dyscrasias Check BUN & creatinine in high risk patients. Remind to increase water intake Acyclovir, valaciclovir, famiciclovir pregnancy cat B Ganiciclovir is pregnancy Cat C

Initiating ART Medications

ART should be initiated in patients with AIDS-defining illness or CD4 count less than 350 cells/mm3 HIV-associated nephropathy Co-infection with hepatitis B infection Pregnant women Patients with CD4 counts between 350 and 500 cells/mm3 Potential benefits of early intervention must be weighed against the risks of early therapy. AIDS-defining clinical conditions (a.k.a. AIDS-defining illnesses or AIDS-defining diseases) is the list of diseases published by the Centers for Disease Control and Prevention (CDC) that are associated with AIDS, and used worldwide as a guideline for AIDS diagnosis. Here is a site with the list of AIDS-defining diseases: Some examples would be Kaposi sarcoma; Cryptococcosis, extrapulmonary; Cryptosporidiosis, chronic intestinal (greater than one month's duration); Cytomegalovirus disease (other than liver, spleen, or nodes) Cytomegalovirus retinitis (with loss of vision) ART regimen is determined by Comorbid conditions Convenience Gender and pretreatment CD4 T-cell count (nevirapine) Genotypic drug resistance testing HLA B*5701 testing if considering abacavir Patient adherence potential Potential adverse drug effects Potential drug interactions with other medications Pregnancy potential

Goals of HIV Treatment

Achieve maximal suppression of plasma viral load for as long as possible. Delay the development of medication resistance. Preserve CD4 T-cell numbers. Confer substantial clinical benefits, leading to reduction in morbidity and mortality. The T helper cells are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses. They are essential in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages. Mature T cells express the surface protein CD4 and are referred to as CD4+ T cells. CD4+ T cells are generally treated as having a pre-defined role as helper T cells within the immune system.

Acyclovir (Zovirax)

Active only against members of the herpesvirus family Agent of first choice for HSV or VZV infection Herpes simplex genitalis Mucocutaneous herpes simplex infections Varicella-zoster infections drug of choice for most infections caused by herpes simplex viruses and varicella-zoster virus. After conversion to its active form, acyclovir suppresses viral reproduction by inhibiting viral deoxyribonucleic acid (DNA) polymerase and by causing premature termination of viral DNA strand growth. Because the active form of acyclovir is not a good inhibitor of human DNA polymerase, cells of the host are spared. ADRS: Intravenous therapy Phlebitis Reversible nephrotoxicity Oral therapy Gastrointestinal Vertigo Topical therapy Stinging sensations Acyclovir is eliminated unchanged by the kidneys. Accordingly, the dosage must be reduced in patients with renal impairment. Intravenous acyclovir can injure the kidneys. Renal damage can be minimized by infusing acyclovir slowly and by ensuring adequate hydration during and after the infusion.

HIV Monitoring

Adherence to medications and medical visits Affective mental health problems Alterations in metabolism of lipids and glucose Cardiovascular risk Hepatitis B and C co-infection High-risk behaviors Immunization status Renal and hepatic function Sexually transmitted infections Somatic signs and symptoms Tobacco, alcohol, and substance use

Adamantanes for Influenza Treatment

Amantadine: dose 100 mg PO BID x 3-5 days; Start within 48 hours of symptom onset *CDC recommends against use for influenza A in US due to resistance Rimantadine: 100 mg PO BID x 3-5 days *CDC recommends against use for influenza A in US Amantadine was useful for prophylaxis and treatment of influenza A infections. CDC recommends against use for influenza A in US due to resistance Neuraminidase inhibitors (oseltamivir and zanamivir) are highly active against all current strains of influenza A and B, whereas the adamantanes (amantadine and rimantadine) are not. Accordingly, the neuraminidase inhibitors are the current drugs of choice for treatment and prophylaxis of influenza.

Gentamycin, tobramycin, amikacin

Aminoglycosides Mechanism of action: Inhibits Protein Synthesis Clinical Uses: Excellent coverage against gram neg. (including pseudomonas). Have synergy with PCN against Staph and enterococcus Adverse events: Nephrotoxicity and ototoxicity Less toxic with once daily dosing Monitor drug levels Monitor kidney function Auditory toxicity symptoms: hearing loss, tinnitus, nausea, vomiting, vertigo

Drugs that inhibit protein synthesis

Aminoglycosides Ansamycins Tetracyclines Glycylcyclines Macrolides & Ketolides Oxazolidinones Lincosamides Phenicols Streptogramins

Antibiotic Choices for Sinusitis

Amoxicillin first line Dose at 80 to 90 mg/kg/day in high-risk children; 45 mg/kg/day in low-risk children Adults: 500 mg three times/day, or High-dose Augmentin For penicillin-allergic patients Children: cefdinir, cefuroxime, or cefpodoxime Adults: doxycycline or respiratory fluoroquinolone (levofloxacin) If symptoms are worsening after 72 hours of treatment, consider bacterial resistance. Switch to Augmentin if amoxicillin was first choice. If started on Augmentin & worsening symptoms: Adults: Consider respiratory fluoroquinolone (levofloxacin). Children: Consider cefdinir, cefuroxime, cefpodoxime

Rifampin

Antimycobacterials binds to the beta subunit of mycobacteria DNA-dependent RNA Resistance develops rapidly to monotherapy. Cross-resistance with INH and ethionamide Pharmacokinetics Well-absorbed orally Metabolism of isoniazid is highly variable and dependent on acetylator status. Rifampin-potent inducer of liver metabolism, be aware when using w/ other meds Streptomycin/capreomycin given in loading dose & maintained with interval IM dosing ADRs INH: peripheral neuropathy INH, rifampin, and pyrazinamide: hepatotoxicity Ethambutol: optic neuritis Streptomycin and capreomycin: ototoxic Rifabutin: ^LFTs, neutropenia, thrombocytopenia, orange secretion discoloration- tears, urine, sweat (harmless) Most are pregnancy category C Drug interactions Many drug interactions Rifampin is an inducer of CYP 450 enzyme. Rifampin is an inducer of CYP 450 enzyme, so it will interact with many drugs just with this med. If you need to order antitubercular meds, you must use most recent CDC TB treatment guidelines, or local health department. You could also refer to an Infectious Disease provider. Clinical use and dosing Follow Centers for Disease Control (CDC) guidelines. Active TB requires four-drug therapy. Preventive therapy with INH Rational drug selection Follow CDC guidelines. Monitoring Directly observed therapy Patient education Importance of taking medication daily Reporting of ADRs

Isoniazid (INH), ethambutol

Antimycobacterials inhibit synthesis of mycolic acids. Resistance develops rapidly to monotherapy. Cross-resistance with INH and ethionamide Pharmacokinetics Well-absorbed orally Metabolism of isoniazid is highly variable and dependent on acetylator status. ADRs INH: peripheral neuropathy INH, rifampin, and pyrazinamide: hepatotoxicity Ethambutol: optic neuritis Streptomycin and capreomycin: ototoxic Rifabutin: ^LFTs, neutropenia, thrombocytopenia, orange secretion discoloration- tears, urine, sweat (harmless) Most are pregnancy category C Drug interactions Many drug interactions Rifampin is an inducer of CYP 450 enzyme. Clinical use and dosing Follow Centers for Disease Control (CDC) guidelines. Active TB requires four-drug therapy. Preventive therapy with INH Rational drug selection Follow CDC guidelines. Monitoring Directly observed therapy Patient education Importance of taking medication daily Reporting of ADRs

Ethambutol

Antimycobacterials inhibits synthesis of arabinogalactan, an essential component of mycobacteria cell walls Resistance develops rapidly to monotherapy. Cross-resistance with INH and ethionamide Pharmacokinetics Well-absorbed orally Metabolism of isoniazid is highly variable and dependent on acetylator status. ADRs INH: peripheral neuropathy INH, rifampin, and pyrazinamide: hepatotoxicity Ethambutol: optic neuritis Streptomycin and capreomycin: ototoxic Rifabutin: ^LFTs, neutropenia, thrombocytopenia, orange secretion discoloration- tears, urine, sweat (harmless) Most are pregnancy category C Drug interactions Many drug interactions Ethambutol: optic neuritis (inflammation of optic nerve). Recommend periodic visual acuity screening. Refer to ophthalmologist if develop symptoms (eye pain which worsens with eye movement, unilateral vision loss, inability to see colors well). Clinical use and dosing Follow Centers for Disease Control (CDC) guidelines. Active TB requires four-drug therapy. Preventive therapy with INH Rational drug selection Follow CDC guidelines. Monitoring Directly observed therapy Patient education Importance of taking medication daily Reporting of ADRs

Macrolide Antibiotics

Azithromycin- unique; does not extensively inhibit CYP3A4 Clarithromycin Erythromycin Telithromicin Fidaxomycin

Sinusitis

Bacteria isolated in 70% of patients with sinusitis Strict criteria: persistent, not improving for at least 10 days Common pathogens S. pneumoniae: 30% H. flu: 20% Moraxella catarrhalis: 20% Rarely, Staphylococcus

STIs: Pelvic Inflammatory Disease

Can result from delayed treatment for STI Difficult to definitively diagnose Treatment: multidrug regimen with empirical, broad-spectrum coverage of the most likely pathogens May need IV antibiotics or hospitalization

Ertapenem (Invanz), doripenem (Doribax), Imipenem (Primaxin), and Meropenem (Merrem)

Carbapenems Mechanism of action: Bactericidal. Inhibits cell wall synthesis Beta-lactam Most broad-spectrum agent available Clinical uses: Gram + and Gram - coverage Staph, strep, pseudomonas, acinetobacter Great for polymicrobial infections Skin, bone, joint, intra-abdominal, and lower resp. infections The carbapenems are beta lactam antibiotics which have a broad spectrum of activity against many gram-positive and gram-negative, aerobic and anaerobic organisms. The carbapenems, like other beta lactam antibiotics, bind to critical penicillin-binding proteins, disrupting the growth and structural integrity of bacterial cell walls. Carbapenems have a fused beta lactam ring that is resistant to most beta lactamases. The carbapenems have excellent activity against streptococci, enterococci, staphylococcci, listeria, enterobacteriaceae, and many pseudomonas, bacteroides and acinetobacter species. However, most methicillin-resistant staphylococci are also resistant to carbapenems. Carbapenems have a safety profile similar to that of other beta lactam antibiotics such as the cephalosporins and the penicillins. The most common adverse effects are injection site reactions, diarrhea, nausea, vomiting, skin rash and pruritus. Adverse Events: Neurotoxicity, Seizure activity Risk factors for seizures: impaired renal function, improper dosing, CNS disorder If the patient has a h/o seizure disorder and this class is needed: choose Merrem over others GI side effects: N/V/D Drug interactions: Don't use with Probenicid imipenem, meropenem,ertapenem are parenteral β lactamantibiotics, β lactamaseresistant. They have broadest spectrum of activity. Mechanism of action: It binds to penicillin binding proteins and disrupts bacterial cell wall synthesis andcauses death of susceptible microorganisms. It is very resistant to hydrolysis by most beta lactamases. Antimicrobial activity Broad spectrum of activity-effective against -veand + aerobic andanaerobic microorganisms, e.g., streptococci ( including penicillin resistant Spneumoniae), enterococci, Enterobacteriaceae, Pseudomonas, Acinetobacter, anaerobes including B. fragilis It is not effective against Enterococcusfaecium, MRSA and Clostridium.difficile

Antimicrobial resistance

Causes of drug resistance Recent use of antibiotics Overuse of broad-spectrum antibiotics Risk Factors Age younger than 2 years or older than 65 years Daycare center attendance Exposure to young children Multiple medical comorbidities Immunosuppression Biggest risk of developing resistance is inappropriate use of antimicrobials; Every class of ABX has some resistant organisms. Most resistance seen among infants & young children r/t more likely in Day Care & exposed to pathogens from other children Check local resistance patterns which can be identified by monitoring the antibiogram (a chart of local resistance patterns to antibiotics developed by a local laboratory). Every antibiotic class has resistance organisms. Local resistance patterns can be identified by monitoring the antibiogram of the local laboratory. Vaccination with pneumococcal vaccine has decreased resistance.

Vaginitis: Pathophysiology

Cytolytic vaginosis Overgrowth of Lactobacillus occurs late in the menstrual cycle Treatment with intravaginal sodium bicarbonate capsules twice weekly in last week of menstrual cycle Atrophic vaginitis with secondary infection Cultures guide treatment.

ART Failure

Defined as the failure to achieve or maintain suppression of viral replication to less than 50 copies/mL May be either failure or virological rebound Causes Suboptimal adherence Toxicity

Vaginitis

Diagnosing vaginal discharge and vulvar conditions requires examination of the area affected and microscopic examination of vaginal secretions. May or may not be sexually transmitted

Discontinuation or Interruption of ART

Discontinuation or interruption of ART is associated with HIV viral rebound, immune decompensation, and clinical progression. Interruption of ART may become necessary. -Concurrent illness -Severe drug toxicity -Surgery that precludes oral therapy -Antiretroviral medication nonavailability

Anthelminthics

Discussion is limited to helminthic infections in the US Pharmacodynamics Intestinal nematodes are treated with mebendazole, pyrantel. Tissue nematodes are treated with mebendazole, thiabendazole, albendazole, or ivermectin. In the United States pinworms are common: 50 million cases per year ADRs Nausea, vomiting, diarrhea, transient abdominal pain, fever & rash Mebendazole & albendazole may cause transient neutropenia & ^LFTs. Ivermectin may cause Mazzotti reaction. Mebendazole & albendazole may cause transient bone marrow suppression with neutropenia & elevated LFT When treating an Onchocerra volvulus infection with Ivermectin may cause Mazzotti reaction (an be life-threatening, and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, edema, and abdominal pain that occur within seven days of treatment). It is not a true ADR. It is related to the death of the organism Clinical use and dosing Pinworms, Whipworms, or Hookworms: single dose of mebendazole, pyrantel pamoate, or albendazole Roundworms: mebendazole Threadworm: ivermectin Scabies: off-label ivermectin in immunocompromised patients Rational drug selection Use CDC recommendations. All agents are pregnancy category C Only use if absolutely necessary in pregnant women Monitoring Assess for the eradication of the helminth. Roundworms, hookworms, and whipworms; stool samples are obtained before and 1 to 3 weeks after treatment for proof of cure Threadworms: Routine stool examination using Baermann technique Patient education Albendazole and mebendazole are given with a high-fat meal. Ivermectin is taken on an empty stomach. Albendazole should not be taken if pregnant and back-up contraception should be used for 1 month after taking.

Ganciclovir

Drug of choice for prophylaxis and treatment of cytomegalovirus (CMV) infection in immunocompromised patients ADR: granulocytopenia and thrombocytopenia the drug of choice for prophylaxis and treatment of CMV infection in immunocompromised patients, including those with acquired immunodeficiency syndrome (AIDS). Ganciclovir does not cure CMV retinitis in patients with AIDS; therefore, in most cases treatment must continue for life. Like acyclovir, ganciclovir becomes activated within infected cells, after which it inhibits viral DNA polymerase and causes premature termination of viral DNA strand growth. Like acyclovir, ganciclovir is excreted unchanged in the urine; therefore, the dosage must be reduced in patients with renal impairment. The major adverse effects of ganciclovir are granulocytopenia and thrombocytopenia.

Antimycobacterials

Drug resistance is a problem with TB therapy. A person with active TB disease has drug resistant TB if the TB bacteria that the person is infected with, will not respond to, and are resistant to, at least one of the main TB drugs. (like INH, rifampin, ethambutol, or pyrazinamide). Therefore, you will rarely see monotherapy to treat TB. However, you could see a patient on preventative therapy with one drug-INH which would usually need to be taken daily for 9 months. You need to know common combo therapy agents. Individuals that differ in their inherited ability to metabolize certain drugs, e.g., isoniazid, are termed fast or slow acetylators. Some people have a genetic deficiency of the enzyme. They are slow acetylators. May need to adjust the dose of INH downward in these patients. About 50% of Americans are slow acetylators and 50% fast. Avg. plasma level is 30-50 times higher in slow acetylators. Fast acetylators may need more drug. Slow acetylators - higher risk for some side effects. Four most commonly used antitubercular meds: isoniazid (INH), ethambutol, rifampin, & pyrazinamide INH: peripheral neuropathy You will often see pyridoxine (Vitamin B6) given to treat neuropathy and also given prophylactically to prevent Ethambutol: optic neuritis (inflammation of optic nerve). Recommend periodic visual acuity screening. Refer to ophthalmologist if develop symptoms (eye pain which worsens with eye movement, unilateral vision loss, inability to see colors well). Streptomycin and capreomycin are aminoglycosides, so watch for ototoxicity & nephrotoxic-so check These drugs have many drug-drug interactions. Rifampin is an inducer of CYP 450 enzyme, so it will interact with many drugs just with this med. If you need to order antitubercular meds, you must use most recent CDC TB treatment guidelines, or local health department. You could also refer to an Infectious Disease provider. You will usually see a four drug treatment regimen. INH is often given as a preventative. May need direct observation therapy (DOT). Check renal & liver function regularly. Get an up to date medication profile regularly. Tell patient to avoid alcohol while taking. Remember they need support.

HIV Medication Resistance

Due to Poor patient adherence to the ART regimen Drug-drug or drug-food interactions Abnormal absorption, distribution, metabolism, or excretion of the medicine First sign of HIV resistance is detectable plasma viral RNA levels. Phenotype assays are used to measure sensitivity to various antiretroviral agents.

STIs: Sexual Assault

Most common infections in assaulted women Trichomoniasis, bacterial vaginosis, gonorrhea, and chlamydia Routine prophylaxis for STIs after a sexual assault is recommended. Post-exposure administration of hepatitis B immune globulin and hepatitis B vaccine Screen for date-rape drugs.

HIV Testing

ELISA Test Saliva Test Viral Load Test Western Blot Home Test People exposed to the virus should get tested immediately. It can take anywhere from six weeks to a year to develop antibodies to the virus. Follow-up tests may be needed depending on the initial time of exposure. If test positive for the virus, develop a treatment plan that can help fight HIV and ward off complications. Alert Pt. to avoid high-risk behavior to reduce spread of the virus. Anonymous and free testing is available. The Centers for Disease Control and Prevention (CDC) recommends that everyone 13 to 64 years old get tested for HIV at least once. People with high risk behaviors should get tested each year. Sexually active gay and bisexual men may benefit from getting tested more often, such as every 3 to 6 months. https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/47/hiv-testing ELISA Test (Enzyme-linked Immunosorbent Assay) is used to detect HIV infection. If an ELISA test is positive, the Western blot test is usually administered to confirm the diagnosis. If an ELISA test is negative, recommend testing again in one to three months. Caution the patient that even if initial test is negative, the individual may have a high level of the virus and be at risk of transmitting infection. Western Blot — This is a very sensitive blood test used to confirm a positive ELISA test result. Saliva Tests — A cotton pad is used to obtain saliva from the inside of the cheek. The pad is placed in a vial and submitted to a laboratory for testing. Results are available in three days. Positive results should be confirmed with a blood test. Viral Load Test —measures the amount of HIV in blood. Generally, it's used to monitor treatment progress or detect early HIV infection. Three technologies measure HIV viral load in the blood: reverse transcription polymerase chain reaction (RT-PCR), branched DNA (bDNA) and nucleic acid sequence-based amplification assay (NASBA). HIV is detected using DNA sequences that bind specifically to those in the virus. Home Tests — The only home test approved by the U.S. Food and Drug Administration is called the Home Access Express Test, which is sold in pharmacies

Genital Lice: Rational Drug Selection

Ectoparasitic infection Treated with pyrethrins (permethrin 1% or pyrethrin lotion, or shampoo) Reapply in 7 days if evidence of lice.

Goals of STI treatment

Educate patients about high-risk behaviors. Especially patients ages 15 and 25 years Prevent long-term sequelae of unsafe sex. Choose the most specific, cost-effective drug that has the best regimen for adherence. Reduce morbidity and provide comfort.

Terbinafine (Lamisil)

Effective treatment for onychomycosis Onychomycosis fingernails: 250 mg PO daily x 6 weeks Onychomycosis toenails: 250 mg. PO daily x 12 weeks Tinea pedis, corporis or cruris: 250 mg. PO daily x 2 weeks ADRs: H/A, elevated ALT/AST hepatotoxicity, hypersensitivity reaction, Stevens-Johnson syndrome, thrombocytopenia, neutropenia, depression Check creatinine & LFT at baseline; Check CBC if > 6 weeks treatment in immunodeficient patients Avoid if hepatic impairment; Avoid if creatinine clearance <50

Granuloma inguinale and treatment

Endemic in tropical and developing areas of India, Papua New Guinea, central Australia, and southern Africa Treatment: doxycycline 100 mg twice daily for 3 weeks Relapse is common within 6 to 18 months.

Drugs that inhibit nucleic acid synthesis

Fluoroquinolones Furanes

STIs: Monitoring

Follow up with patients who are treated. Especially those who are on multiple-day treatment regimens Test of cure or rescreening as previously mentioned Most STIs are reportable to local health department, so inform patient. Partner treatment

HPV: Rational Drug Selection

Forty viral types Eleven strains are associated with warts. Five strains (16, 18, 31, 33, and 35) are associated with cervical neoplasia. Treatment of genital warts Patient-applied therapy: podofilox 0.5% solution or gel or imiquimod 5% cream Provider-applied therapy: cryotherapy with liquid nitrogen or cryoprobe or podophyllin resin or trichloroacetic acid or bichloroacetic acid Prevention of HPV infection Vaccinate males and females with Gardasil 9. If sexually active: Recommend condom use during every sexual encounter. This lowers risk of contracting HPV. But, HPV can infect areas not covered by a condom. Recommend mutually monogamous relationship. HPV Vaccines per CDC website: Quadrivalent HPV vaccine (Gardasil[28 pages]) is a non-infectious recombinant vaccine prepared from the purified virus-like particles (VLPs) of the major capsid (L1) protein of HPV types 6, 11, 16, and 18. Cervarix inly covers HPV types 16 & 18 9-valent HPV vaccine (Gardasil-9[23 pages]), is a non-infectious recombinant vaccine prepared from the purified VLPs of the major capsid (L1) protein of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

STIs: Men Who Have Sex With Men

Frequent screening of high-risk males Every 3 to 6 months Vaccinate against hepatitis A, hepatitis B and HPV. Same treatment for infections as heterosexuals who are infected

Mycobacteria

Grow slowly and are relatively resistant to drugs that are largely dependent on how rapidly cells are dividing Have a lipid-rich cell wall relatively impermeable to many drugs Are usually intracellular and inaccessible to drugs that do not have good intracellular penetration Have the ability to go into a dormant state Easily develop resistance to any single drug

Pathophysiology of HIV

HIV induces defects in host cell-mediated and humoral responses. The person becomes susceptible to opportunistic infections and certain neoplasms. AIDS is characterized by progressive immune suppression leading to opportunistic diseases. HIV-1 is responsible for human HIV infections. Rapid dissemination into lymph system and organs after initial infection Host immune response limits viral replication initially Progression to AIDS in average 10 years if not treated HIV-2 is a zoonosis. Lower transmission rate Less pathogenic Transmission: blood, sexual contact, and mother-to-child (vertical) transmission Zoonoses are infectious diseases of animals (usually vertebrates) that can naturally be transmitted to humans.

HIV Cost Considerations

HIV medications are expensive. Medication costs vary widely. Patients may be eligible for state AIDS Drug Assistance Programs (ADAPs). -Congress mandates funds be used for ADAPs. Pharmaceutical companies have co-pays to provide financial assistance.

Human Papillomavirus

HPV - most common sexually transmitted infection (STI). So common that nearly all sexually active people contract it at some point in lifetime. Some strains cause genital warts and cancers. Spread via vaginal, anal, or oral sex with infected individual

Topical drugs

Herpes labialis Penciclovir (Denavir) Docosanol (Abreva) Ocular herpes infections Trifluridine (Viroptic) Vidarabine (Vir-A)

Populations at risk of STI

Highest rates of gonorrhea/chlamydia (GC) in females 15 to 24 years Black women have 8 times higher rate than white women. Black men have 12 times higher rate than white men. 50 million people in the United States have genital herpes simplex virus (HSV).

STI as a precursor to cancer

Human papilloma virus (HPV) cervical cancer is leading cause of female cancer death worldwide.

HIV

Identified in 1981 25 million deaths worldwide 33 million people living with HIV 90% in Sub-Saharan Africa More than 1.1 million people in the U.S. are living with HIV today, and 1 in 7 of them don't know it. An estimated 37,600 Americans became newly infected with HIV in 2014. From 2005 to 2014, the estimated number of annual HIV infections in the U.S. declined 18%. Gay and bisexual men, particularly young African American gay and bisexual men, are most affected. Southern states bear the greatest burden of HIV, accounting for 50% of new infections in 2014. In the jurisdictions where they could be estimated, annual infections in all states decreased or remained stable from 2008-2014. LIVING with HIV: At the end of 2013, the most recent year for which such data are available, an estimated 1,242,000 adults and adolescents were living with HIV. An estimated 161,200 (13%) had not been diagnosed. Young people were the most likely to be unaware of their infection. Among people aged 13-24, an estimated 51% (31,300) of those living with HIV didn't know.

Drugs that inhibit membrane functions

Leptopeptides Polymyxin

Clindamycin (Cleocin)

Lincosamides Pharmacodynamics: inhibits protein synthesis No gram-negative activity Gram-positive activity: corynebacterium acnes, gardnarella vaginalis, some methicillin-resistant Staphylococcus aureus (MRSA) Pharmacokinetics: oral dosing completely absorbed, not affected by gastric acid ADRs: boxed warning for severe colitis; dermatological: rash, burning, itching, erythema; transient eosinophelia, neutropenia, thrombocytopenia Lincamycin is also in this class, but you will not see it used frequently in clinical setting. Be aware of your patient's hepatic function. May need to adjust dose if hepatic impairment If patient has colitis & you prescribe, tell your patient to RTC ASAP if diarrhea develops Clinical use and dosing First-line therapy for MRSA in some areas Infections in PCN-allergic patients Drug-resistant Streptococcus Pneumoniae infections Dental infections Rational drug selection Considered second-line therapy, narrow spectrum of aerobic activity First-line therapy in special populations (pregnancy and children) Use for MRSA depending on local drug resistance in the area Considered a 2nd line therapy when don't know organism. Can be used to treat bacterial vaginosis in pregnant women but would use cautiously in nursing MOMs. It can be used for children if serious infection & other less toxic ABX not appropriate Monitoring Stop medication if significant diarrhea occurs. Patient education Finishing therapy ADRs: diarrhea Advise about adverse effects such as nausea, vomiting, bitter taste in mouth & most serious-C Diff colitis, stop & to call provider diarrhea if severe.

Vancomycin, telavancin (Vibativ), dalbavancin (Zeven)

Lipoglycopeptides Pharmacodynamics Used for severe gram-positive infections, such as MRSA-resistant to first-line antibiotics (DOC for MRSA) Inhibits cell wall synthesis Pharmacokinetics Poor oral absorption, given IV ADRs Ototoxicity (transient or permanent) Nephrotoxicity "Red Man" syndrome if infused too fast Vancomycin is most common. PO vancomycin has been used to treat C-Diff infections You must know kidney function before initiating Serum drug monitoring Vancomycin trough 30 min prior to 4th dose. If in range, draw weekly trough for duration of treatment General range: 10-20 mg/mL Draw a baseline Creatinine Continue to monitor kidney function weekly Clinical use and dosing Serious gram-positive infections resistant to other medications IV is pregnancy category C Monitoring Hearing and renal function Patient education Administration ADRs The goal is to prevent damage by being proactive with medication dosing. At the peak, large amounts are circulating, and at the trough, the levels fall very low. Providers must time dosing with the goal of keeping levels consistent by delivering medication before concentrations reach a trough. Example: With vancomycin, the drug trough level is most commonly monitored especially if > 4 days of med needed, or receiving other nephrotoxic meds. Trough drawn 30 minutes prior to next dose. Draw peak level of vancomycin at least 1 hour past dose administered.

Rationale for ART Medication Selection

More than 20 U.S. Food and Drug Administration- approved ART drugs Treatment of HIV disease is a dynamic, rapidly changing arena. HIV medications are always used in combination to reduce the amount of HIV in the blood. Antiretroviral therapy (ART) drugs when taken in combination can prevent the growth of the HIV virus. When the virus is slowed down, so is HIV disease.

Bacterial Vaginosis (BV): Rational Drug Selection

Most prevalent vaginal infection BV is associated with having multiple sex partners, douching, and lack of vaginal lactobacilli. All symptomatic women should be treated. Treatment Metronidazole: 500 mg by mouth twice daily for 7 days, or Metronidazole gel, 0.75%: one applicator full intravaginally daily for 5 days, or Clindamycin cream, 2%: one applicator full intravaginally at bedtime for 7 days BV is the most common vaginal infection affecting young women. Although it's not considered a sexually transmitted disease (STD), the chances of developing bacterial vaginosis seem to increase with the number of a woman's sexual partners. BV increases risk of contracting other STIs Not treating BV will increase chance of: developing pelvic inflammatory disease (PID) which can cause infertility; delivering baby too early if BV while pregnant; contracting HIV; If already HIV positive, will increase chance of passing HIV to partner.

Noninfectious Vaginal Conditions

Normal cyclical hormonal changes may cause changes in vaginal secretions. Irritant or allergic reaction to products Atrophic conditions in postpartum period, lactation, or post-menopause

Gonorrhea and rational drug selection

Often co-infected with chlamydia, so treat for both. Screen 15-24 year-olds & Pt with other STIs Ceftriaxone 250 mg intramuscular (IM) one time is the drug of choice. May use cefixime 400 mg by mouth one time. Resistant to fluoroquinolones Treat sexual partners. Repeat screening of women 3 to 6 months after treatment. Pathogen: gram negative diplococcus (Neisseria gonorrhoeae) 2nd most common bacterial STD. Chief c/o purulent discharge. Symptoms: men-urethritis, dysuria, purulent discharge, painful, swollen testicles. Women- urethral discharge, cervicitis, vag discharge, dysuria, abdominal pain Sequelae: Urethritis; Cervicitis; Dysuria

Principles of HIV Therapy

Ongoing HIV replication leads to immune system damage and progression to AIDS. Plasma HIV ribonucleic acid (RNA) and CD4 T-cell levels must be regularly measured (every 3 to 6 months). Treatment decisions should be individualized based on the risk of disease progression as indicated by plasma HIV RNA levels and CD4 measurements. *Goal of therapy should be the maximum achievable suppression of HIV replication.* Most effective way to achieve sustained suppression of HIV replication is the combination of effective anti-HIV medications.

Neuraminidase Inhibitors

Oseltamivir (Tamiflu): 75 mg. PO bid x 5 days for flu treatment; 75 mg. PO bid x 10 days for prophylaxis Zanamivir (Relenza): 5 mg. powder tablets given per disk haler. Flu treatment: 2 puffs q 12 hours x 5 days Prophylaxis: 2 puffs inhaled q 24 hours x 10 days Per CDC (2017): 99% of circulating flu in US is Oseltamivir & zanamivir susceptible Oseltamivir: 75 mg. PO bid x 10 days for prophylaxis. Start within 48 hours after household exposure, give for 7 days for other exposures Zanamivir

Antiviral Therapy

Our ability to treat viral infections remains limited Viruses use biochemical machinery of host cells to reproduce Difficult to suppress viral replication without doing significant harm to the host Antivirals suppress biochemical processes unique to viral reproduction

Linezolid, Tedizolid

Oxazolidinones Pharmacodynamics Inhibits bacterial ribosomal protein synthesis Most effective against gram-positive bacteria Resistance emerging Pharmacokinetics Well-absorbed orally Does not use CYP 450 enzymes ADRs Diarrhea, H/A, nausea; Myelosuppression reported-resolves w/ drug discontinuation. Check CBC if treatment> 2 weeks Clinical use and dosing Pneumonia Complicated skin infections Use less expensive drugs first Rational drug selection Expensive ($1,152 for 20) Patient education Administration ADRs Clinical Use Pneumonia, complicated skin infections Use less expensive drug first Pregnancy Category C Patient Education Complete the entire series. Avoid tyramine-rich foods. Avoid MAO inhibitor meds with oxalodinones

STIs: Special Treatment Considerations

Pregnant women All women should be screened for STIs. Not all drugs are safe in pregnancy. Children Children with STIs are considered abused until proven otherwise. Adolescents High-risk population Screen liberally. Know laws regarding treatment in your state.

Scabies: Rational Drug Selection

Parasite causes intense pruritus. Passed between sexual partners or by sharing bed Treatment Permethrin 5% cream is drug of choice. Lindane is second-line treatment. Ivermectin 200 mcg/kg by mouth can be prescribed for immunocompromised or those who have refractory scabies (consultation recommended). Sexual contacts and family members should be treated. Symptoms of scabies include an intense pruritis that is usually worse at bedtime. You may see small, fine, wavy lines on the skin with a tiny insect at the end (a burrow). Burrows are usually found on finger/toe webs, wrists, elbows, armpits, belt line, lower buttocks, female nipples, or male genitals. Even if the med kills all the scabies, the dead mites can still make patient itch for up to 4 weeks after treatment. Apply permethrin from head to the soles of feet, including under nails and in skin folds such as between the toes, as directed. Massage the cream into the skin. Do not use more medication than prescribed. Wash off the cream after 8-14 hours by showering or taking a bath. Avoid getting the cream into eyes, nose, mouth, or vagina.

STIs: Penicillin Allergy

Penicillin is drug of choice for neurosyphilis, congenital syphilis, syphilis in pregnant women, or HIV-infected patients. Refer to allergy specialist for skin testing and desensitization.

Beta-Lactam Antibiotics

Penicillins Cephalosporins Monobactams Carbapenems Glycopeptides Fosfomycin All antibiotics in this category (penicillins, cephalosporins & certain miscellaneous compounds) contain a beta lactam ring that is essential for activity but is also susceptible to hydrolysis by beta-lactamases, destroying the antimicrobial action of the compound. (Some agents are resistant to destruction by the beta lactamases). Beta-lactamase-producing staphylococci cause about 80% of community-acquired staph infections. Beta Lactam ABX are bactericidal when concentrations exceed the minimum inhibitory concentration (MIC) for the pathogen for 50% of the dosing interval. Monobactams & carbopenems are used for treating serious infections and are administered to inpatients. The beta-lactam ring is where beta-lactamase (enzyme) does its thing to decrease the effectiveness of the ABX. If the antibiotic is susceptible to hydrolysis by beta-lactamases, the antimicrobial action of the compound will be destroyed. Ampicillin & amoxicillin are aminopenicillins. They treat gram-positive organisms (Streptococcus & Enterococcus species). But they have greater activity against gram-negative bacteria because of their ability to penetrate the outer membrane of the organism. Due to increasing beta-lactamase production among gram-neg pathogens, the aminopenicillins often need to be combined with a beta-lactamase-inhibitor. The beta-lactamase inhibitors prevent destruction of beta-lactam ABX by serving as a competitive inhibitor of beta-lactamase.

Influenza

Per the CDC, there are four types of influenza viruses: A, B, C and D. Human influenza A and B viruses cause seasonal epidemics of disease almost every winter in the United States. The emergence of a new and very different influenza A virus to infect people can cause an influenza pandemic. Influenza type C infections generally cause a mild respiratory illness and are not thought to cause epidemics. Influenza D viruses primarily affect cattle and are not known to infect or cause illness in people. Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes. (H1 through H18 and N1 through N11 respectively.) Influenza A viruses can be further broken down into different strains. Current subtypes of influenza A viruses found in people are influenza A (H1N1) and influenza A (H3N2) viruses. In the spring of 2009, a new influenza A (H1N1) virus (CDC 2009 H1N1 Flu website) emerged to cause illness in people. This virus was very different from the human influenza A (H1N1) viruses circulating at that time. The new virus caused the first influenza pandemic in more than 40 years. That virus (often called "2009 H1N1") has now replaced the H1N1 virus that was previously circulating in humans. Vaccination is the best way to prevent influenza. Two types of antiviral drugs to treat influenza: Neuraminidase inhibitors Adamantanes Neuraminidase Inhibitors (oseltamivir and zanamivir) Adamantanes (Amantadine and rimantadine) Vaccination is the best way to prevent influenza. Because influenza viruses evolve rapidly, influenza vaccines must be reformulated each year, and persons wanting protection must receive the new vaccine each year. Two types of influenza vaccines are available: inactivated influenza vaccine (administered by intramuscular [IM] injection or intradermal injection) and live, attenuated influenza vaccine (LAIV) (administered by nasal spray). Neuraminidase inhibitors (oseltamivir and zanamivir) are highly active against all current strains of influenza A and B, whereas the adamantanes (amantadine and rimantadine) are not. Accordingly, the neuraminidase inhibitors are the current drugs of choice for treatment and prophylaxis of influenza

Antivirals: Nucleoside Analogues

Pharmacodynamics Antiviral drugs must either block entry into the cells or be active inside host cells to be effective. Acyclovir: active against herpes simplex viruses 1 and 2 (HSV-1 and HSV-2); varicella-zoster virus (VZV); Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes virus 6 Valacyclovir is converted to acyclovir after oral administration and is active against the same viruses. Famciclovir: active against HSV-1 and HSV-2, VZV, EBV, and hepatitis B virus Ganciclovir is active against CMV. Antiviral drugs must either block entry into the cells or block replication within the host cells to be effective. Acyclovir is the most notable & easily recognized drug in this class. It was also the first of its class, so has been on the market the longest. It has a fairly short half-life so is dosed 5 times a day Valacyclovir has a longer half-life so is dosed BID Ganciclovir is used to treat CMV eye infections in immunocompromised patients. It is used to prevent CMV infection in certain organ transplant patients.

Valacyclovir (Valtrex)

Prodrug form of acyclovir Herpes zoster Herpes simplex genitalis Herpes labialis In some immunocompromised patients Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)

Famciclovir (Famvir)

Prodrug used to treat acute herpes zoster or genital herpes infection Benefits are equivalent to those of acyclovir Adverse effects are minimal

Systemic Azoles and Other Antifungals

Pharmacodynamics Macrocyclic Polyenes: amphotericin B and nystatin Azoles have broad spectrum activity: butoconazole, clotrimazole, ketoconazole, minonazole, terconazole, tioconazole, fluconazole, itraconazole Allylamines active against yeast and dermatophytes: naftifine, terbinafine Nuclear acid synthesis inhibitors: flucytosine Griseofulvin There are 4 main classes of antifungal drugs: Macrocyclic Polyenes (amphoreicin B) Azoles (2 subgroups: imidazoles (topicals) & triazoles (like fluconazole) Allylamines-like terbinafine (Lamisil) Nuclear acid synthesis inhibitors (flucytosine) to treat Cryptococcus infections Griseofulvin is a miscellaneous antifungal & is an older medication. We will not focus on this med during this lecture Pharmacokinetics Oral absorption varies per agent Fluconazole is an inhibitor of CYP 450 3A4 and 2C9. Itraconazole is an inhibitor of CYP 450 3A4. Ketoconazole is an inhibitor of CYP 450 3A4. Absorption of itraconazole is enhanced by food. Absorption of griseofulvin is enhanced by fat. ADRs All of the azoles and terbinafine have been associated with hepatotoxicity. Drug interactions Multiple due to CYP 450 3A4 inhibition Fluconazole is an inhibitor of CYP 450 and is mainly cleared by renal excretion; others are excreted via kidneys in varying degrees. You should therefore be aware of your patient's renal function before starting a course of azoles and recheck periodically during prolonged therapy. All of the azoles and terbinafine have been associated with hepatotoxicity, so you will need to be checking LFTs Clinical use and dosing Oral antifungals used to treat superficial infections by yeasts (Candida, pityriasis versicolor) and dermatophytes (tinea infections) and invasive systemic mycoses Fluconazole requires loading dose. Rational drug selection Fluconazole has the fewest drug interactions of azoles & can be used to treat children & infants Azoles are pregnancy category C except voriconazole which is category D; terbinafine is category B Diflucan is used to treat infections caused by fungus, which can invade any part of the body including the mouth, throat, esophagus, lungs, bladder, genital area, and the blood. The treatment course length can vary per disease process and azole being used. Remind your patient that response to an antifungal can be longer than the response they would to antibiotic treatment. . Prolonged therapy measure LFT prior & q 3-4 months. Fungi grow slower than bacteria and therefore take longer to treat Monitoring Ketoconazole: aspartate amino transferase, alanine aminotransferase, alkaline phosphatase, and bilirubin before and every 3 to 4 months Patient education Instruct to take with food. Discourage alcohol use. Educate regarding signs of liver toxicity

Metronidazole, Nitazoxanide, Tinidazole

Pharmacodynamics Metronidazole/ Tinidazole inhibit DNA and protein synthesis. Nitazoxanide interferes w/ PFOR enzyme-dependent electron transfer reaction Pharmacokinetics *Oral forms rapidly absorbed *Metronidazole-60-80% excreted via kidneys; nitazoxanide excreted 66% in feces/33% in urine; tinidazole mostly excreted by liver and lesser amount via kidneys. Metronidazole treats both parasitical and bacterial infections. Metronidazole is active against Trichomonas vaginalis, Entamoeba histolytica, H. pylori, Clostridium, C. difficile Nitazoxanide (Alinia) is used to treat Giardia lamblia and Cryptosporidium. Nitazoxanide is an anti-parasite drug which treats diarrhea caused parasitic infection. Tinidazole (Tindamax) is active against amebiasis, giardiasis, and trichomoniasis. ADRs All 3 Meds: anorexia, nausea, abdominal pain. Metronidazole: dizziness, headache, metallic taste Clinical use and dosing Metronidazole and tinidazole are used against the protozoal infections T. vaginalis, G. lamblia, and E. histolytica. Metronidazole is used for anaerobic bacterial infections, bacterial vaginosis, and is one of the drugs in H. pylori treatment. Metronidazole/nitazoxanide pregnancy category B; tinidazole pregnancy category C Rational drug selection Metronidazole is on $4 retail lists. Avoid metronidazole in first trimester of pregnancy. Used inpatient & outpatient treatments. Flagyl and Flagyl ER (metronidazole) are the available brand names for metronidazole. It is used to treat parasitic infections including Giardia infections of the small intestine, amebic liver abscess, and amebic dysentery (infection of the colon causing bloody diarrhea), bacterial vaginosis, trichomonas vaginal infections, and carriers of trichomonas (both sexual partners) who do not have symptoms of infection. Metronidazole is also used alone or in combination with other antibiotics in treating abscesses in the liver, pelvis, abdomen, and brain caused by susceptible anaerobic bacteria. Used in treatment of C. difficile. Flagyl vaginal gel is used for treating bacterial vaginosis. Flagyl topical gel is used for treating rosacea Monitoring Resolution of symptoms Signs of leukopenia Patient education Administration-take with food Metallic taste with metronidazole Treat partner if STI Avoid alcohol if taking metronidazole or tinidazole due to disulfiram-like reaction. Concurrent treatment of partner if sexually transmitted infection With metronidazole can see CNS issues and some peripheral NS symptoms-particularly with long-term use Treat partner-if a Trichomonas infection, treat w/ metronidazole 2 grams po x 1 dose; patient should abstain from intercourse until both partner are treated & should be retested in 3 months because of high reinfection rate

Antivirals for Influenza

Pharmacodynamics Oseltamivir (Tamiflu), peramivir (Rapivab), zanamivir (Relenza) are used to treat influenza A and B. Sensitivity varies by year. Resistance to amantadine and rimantadine is common, no longer recommended for influenza. Pharmacokinetics Oseltamivir is well-absorbed after oral administration. Zanamivir is inhaled, 4% to 17% absorbed. Peramivir is administered IV. Oseltamivir (Tamiflu), peramivir (Rapivab), zanamivir (Relenza) are used to treat influenza A and B. Sensitivity varies by year. Resistance to amantadine and rimantadine is common, no longer recommended for influenza Amantadine (Symmetrel) and rimantadine (Flumadine) are FDA approved for prevention & treatment of respiratory infections caused by influenza A virus. However, CDC no longer recommends their use due to high levels (up to 92%) of resistance to influenza A (Flores, et al, 2011). We will not discuss amantadine (Symmetrel) and rimantadine (Flumadine). ADRs Zanamivir: bronchitis and shortness of breath Oseltamivir: nausea/vomiting Clinical use and dosing Oseltamivir, zanamivir are approved for the prophylaxis and treatment of influenza type A and B. Oseltamivir approved for children 2 weeks old and older. Zanamivir approved for 7 y.o. and older Peramivir is approved for acute influenza in those 18 years and older. Routine prophylaxis with neuraminidase inhibitors not recommended by CDC CDC updates prescribing recommendations annually. Zanamivir=Relenza. ADR of bronchitis and shortness of breath (use cautiously w/ COPD & asthma patients) Oseltamivir=Tamiflu Rapivab® (peramivir injection) is an influenza virus neuraminidase inhibitor indicated for the treatment of acute uncomplicated influenza in patients 18 years and older. Oseltamivir inhibits the neuraminidase enzyme, which is expressed on the viral surface. The enzyme promotes release of virus from infected cells and facilitates viral movement within the respiratory tract. In the presence of neuraminidase inhibitors, virions stay attached to the membrane of infected cells and are also entrapped in respiratory secretions Monitoring Renal function in elderly and debilitated patients Older patients: evaluate for confusion, hallucinations, and cognitive impairment Patient education Start at earliest sign of infection Take full course of therapy. ADRs Advise annual influenza vaccination

Sulfonamides, Trimethoprim, Nitrofurantoin, Fosfomycin

Pharmacodynamics Sulfonamides block folic acid synthesis, trimethoprim inhibits DNA synthesis Nitrofurantoin may inhibit acetyl coenzymes. Inhibit both gram-positive and gram-negative bacteria: E. coli, S. pyogenes, S. pneumoniae, H. influenza, and some protozoa Resistance an issue Fosfomycin inactivates enolpyruvyl transferase ADRs: GI (all 4 meds) - anorexia, n/v, diarrhea, abdominal pain; jaundice/hepatitis w/ sulfonamides & nitrofurantoin only. Stomatitis, rashes, increased hypersensitivity reactions, Stevens-Johnson Syndrome, photosensitivity occur w/ TMP/SMZ CNS/PNS: (TMP/SMZ, nitrofurantoin) - headache, dizziness, peripheral neuropathy Drug interactions: Sulfonamides-avoid in G6PD deficiency. These meds can all be used to treat UTIs. Use cautiously in Pt w/ renal insufficiency. Nitrofurantoin, Fosfomycin used exclusively for UTI treatment Sulfonamides included in this class are sulfathiazole, sulfamethazine (sulfadimidine), sulfamerazine, sulfadiazine, sulfapyridine, sulfabromomethazine, sulfaethoxypyridazine, sulfamethoxypyridazine, sulfadimethoxine, and sulfachlorpyridazine. Concentrate on: Trimethoprim-sulfamethoxazole (TMP/SMX), Trade name: Bactrim, Septra. **Use of Sulfonamides in G6PD deficiency Pt can result in life-threatening bone marrow suppression. G6PD deficiency occurs when a person lacks or insufficient glucose-6-phosphate dehydrogenase (G6PD). This enzyme (G6PD) helps red blood cells work properly. Insufficient G6PD leads to RBC destruction (hemolysis). Red blood cell destruction can be triggered by infections, severe stress, certain foods (such as fava beans), and certain drugs, including: Antimalarial drugs Aspirin Nitrofurantoin Nonsteroidal anti-inflammatory drugs (NSAIDs) Quinidine Quinine Sulfa drugs Clinical use and dosing Most commonly used with UTI infections MRSA is susceptible in some areas Use cautiously w/ renal impairment TMP/SMZ =Pregnancy category C Nitrofurantoin, Fosfomycin= Pregnancy category B Rational drug selection Low-cost alternative in children less than 2 months and PCN allergies Monitoring Control and status if treating UTI. May need urine C&S to determine optimal ABX Long-term use check CBC (blood dyscrasias w/ TMP/SMZ & nitrofurantoin) CMP for liver/renal function Chest x-ray for patients that develop a cough when on nitrofurantoin Patient education: finish course, ADRs, resistance, TMP/SMZ increase daily fluid intake Other clinical uses for trimethoprim/sulfamethoxazole (TMP/SMX): Acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenza: Bacterial meningitis, Pneumocystis (Carinii) Jiroveci Pneumonia; Sepsis; Shigellosis, Skin and soft tissue infection-can be used to treat MRSA-if MRSA is susceptible to TMP/SMX in your area **Chest x-ray for patients that develop a cough when on nitrofurantoin because can cause pulmonary fibrosis.

Macrolides, Azalides, Ketolides

Pharmacodynamics: erythromycin Inhibits ribonucleic acid (RNA)-dependent protein synthesis Weak bases, activity increases in alkaline media, inhibited by acids (require enteric coating) Atypical and intracellular organisms commonly resistant to beta-lactam antibiotics are often susceptible. Cross-resistance seen to all agents in class Pharmacokinetics: well-absorbed from duodenum Potent inhibitors of CYP 450 3A4 Combination with statins may increase risk for myopathy. Exhibit enterohepatic recycling, which can lead to buildup in the system and can cause n/v; tissue levels are higher than serum levels Well absorbed by duodenum. Metabolized by liver; excreted in bile & urine. * Clarithromycin eliminated mostly by kidneys This class is mostly referred to as macrolides (Macrolides, Azalides, Ketolides). Check hepatic function if prolonged use. These are often the DOC for patients severely allergic to PCN. Would avoid use if patient has liver dysfunction Precautions and contraindications Most are safe in pregnancy and children Azithromycin & erythromycin are pregnancy category B, all others in this class are pregnancy category C ADRs Dose-related GI: n/v, abdominal pain, cramping, diarrhea Skin: urticaria, bullous eruptions, eczema, Stevens-Johnson syndrome Cardiac: prolong QT interval Drug interactions Inhibitors of CYP 3A4 Like other macrolide antibiotics, azithromycin has been linked to two forms of hepatotoxicity. The first is an acute, transient and asymptomatic elevation in serum aminotransferases which occurs in 1% to 2% of patients treated for short periods, and a somewhat higher proportion of patients given azithromycin long term. Be aware that because azithromycin has become so commonly used, it has also become one of the more common causes of drug induced liver injury. Clinical use and dosing Drug of choice for community-acquired pneumonia (mycoplasma) Chlamydia-azithromycin Pertussis-azithromycin, clarithromycin or erythromycin H. Pylori infections (clarithromycin) Chronic bronchitis Rational drug selection Often as alternatives for PCN allergies Increasing resistance Not appropriate for treating AOM or sinusitis Chlamydia is treated w/ azithromycin 1 gram po x1 or doxycycline 100 mg po BID x 7 days. If allergic to these meds, can treat with levofloxacin 500 mg po daily or ofloxacin 300 mg BID x 7 days Legionnaires Disease: Historically, erythromycin, one of the original macrolide antibiotics, was used for L pneumophila infection. Currently, however, other antibiotics, including doxycycline, tigecycline, azithromycin, and a respiratory quinolone, are preferred, because they are more active against LD activity and have superior pharmacokinetic properties (eg, better bioavailability, better penetration into macrophages, longer half-life). For severe disease, a fluoroquinolone is recommended. With doxycycline or fluoroquinolones, rifampin does not need to be added in severely ill patients. Monitoring For altered response to concurrent medications metabolized by CYP450; CYP3A4; or CYP2C9 Hepatic/renal impairment Hearing loss Patient education ADRs Drug interactions Fidaxomicin (not a typical macrolide) Specifically used for c-Difficile Minimally absorbed Be careful when you order a macrolide when they are on other meds metabolized by CYP 450 3A4 or 2C9. Example would be simvastatin with macrolide Fidaxomicin (not a typical macrolide) Specifically used for c-Difficile Minimally absorbed

Fluoroquinolones

Pharmacodynamics: interfere with bacterial enzymes required for the synthesis of bacterial DNA Noted for extensive gram-negative activity Not recommended for children less than 18 years of age. Increasing resistance due to overprescribing Can no longer be used for gonorrhea Resistant tuberculosis (TB) Please be aware should not be used in children < 18 years of age due to evidence of tendon and joint issues Pharmacokinetics Well-absorbed; take on empty stomach for best absorption. Metabolism & excretion varies widely in this class ADRs Black Box warning for tendonitis/tendon rupture Elderly at higher risk Can have delayed onset, 120 days to months after administration GI: pseudomembranous colitis Central nervous system (CNS): sleep disorders, dizziness, acidosis Renal/hepatic failure Cardiovascular: angina, atrial flutter Avoid in pregnancy. Category C Do not prescribe to children less than 18 years of age. Big popularity was the once a day dosing. But, with time and use, problems with the drug arose. If a patient who is taking fluoroquinolones presents with tendinopathy, treatment with this drug should be discontinued immediately, and an alternative, nonquinolone antibiotic should be considered. Recovery from fluoroquinolone-related tendinopathy is sometimes slower than from other types of tendinopathy and may require a less aggressive approach in the early stages of rehabilitation. Use in pregnancy can cause bone and cartilage malformation in fetus Clinical use and dosing Complicated UTI, pyelonephritis infections, chronic bacterial prostatitis Pneumonia/chronic bronchitis exacerbation PCN-resistant S. pneumoniae, skin infections, bone/joint infections, complicated intraabdominal, infectious diarrhea Monitoring: watch for prolonged use, ECG with at-risk patients before prescribing moxifloxacin, alcohol use, monitor for tendonitis/rupture When prescribing, please keep in mind the local resistance to fluoroquinolones. Also check if pregnancy capable or pregnant. Pregnancy category C. With prolonged use, watch for renal and hepatic function changes. Potential for prolonged Q-T Should not prescribe if patient has myasthenia gravis monitor for tendonitis/rupture because can happen after course is completed Patient education Food delays absorption. Many drug interactions Take with full glass of water. May cause dizziness If tendon tenderness occurs, stop medication and notify provider.

Trichomoniasis and rational drug selection

Protozoa infection Women may be symptomatic. Men may harbor trichomonas in the prostate gland. Treatment: metronidazole 2 gm by mouth one time or tinidazole 2 gm by mouth one time May also use: metronidazole 500 mg twice daily for 7 days Avoid alcohol while on metronidazole. Topical treatment no longer recommended Rescreen 3 months after treatment. Pregnant women are rescreened in 1 month. Sexual partners are treated.

Lymphogranuloma Venereum

Rare in the United States Diagnosis is made serologically. Treatment: doxycycline 100 mg twice daily for 21 days Pregnant women treated with erythromycin Sexual partners who had contact with the patient in the past 60 days should be examined and treated.

Herpes Simplex Virus and Antiviral Therapy

Remember, we can treat the outbreak of HVV (oral or genital), but we cannot cure it. The virus lies dormant and a lesion can occur during times of stress.

Sinusitis: Patient Education

Saline nasal spray or drops Liquefies secretions Decreases crusting near the sinus ostia Topical decongestants Decrease tissue edema and nasal resistance, probably enhances drainage of secretion from sinus ostia Corticosteroids Helpful in chronic sinusitis No evidence for use in acute sinusitis A sinus ostium is the opening that connects a sinus to the nasal cavity itself. It is a tight area that tends to have a higher percentage of cilia than the surrounding mucosa. If the sinus ostium is blocked this will cause an accumulation of fluid in the sinus.

Syphilis and rational drug selection

Screen high-risk patients and all pregnant women. Parenteral penicillin G is the drug of choice. Adult: 2.4 million Units IM x 1 dose If penicillin-allergic, treat with 14 days of doxycycline or tetracycline. Syphilis Pathogen: spirochete, Treponema apllidum, that rapidly penetrates intact mucous membranes or microscopic dermal abrasions. Pentrates lymphatics and blood to produce systemic illness. Sequelae: Cardiovascular complications Neurologic disease, Congenital syphilis. Primary, Secondary and Early latent Syphilis: Parenteral Benzathine Penicillin G is drug of choice Adult: 2.4 million Units IM x 1 dose. Late Latent or Tertiary Syphilis: Parenteral Benzathine Penicillin G is drug of choice Adult: 2.4 million Units IM x once a week x 3 doses Penicillin allergy: Doxycycline 100 mg BID x 14 days, tetracycline 500 mg four times daily x 14 days, or azithromycin 2 g x 1 dose. **Desensitization should be performed in young children or if pregnant Follow up in 6 months Clinical examination Test titers

Medications Used to Treat HIV

Six "families" of HIV antiretroviral drugs Nucleoside reverse transcriptase inhibitors Nonnucleoside reverse transcriptase inhibitors Protease inhibitors Fusion inhibitors Integrase strand transfer inhibitor CCR5 antagonists Most of the medications used to treat HIV cause multiple side effects & ADRs. The Nucleoside reverse transcriptase inhibitors can cause: decreased bone density, new or worsened kidney disease, nausea and vomiting, hepatic steatosis (fatty liver), lipodystrophy (abnormal distribution of body fat), nervous system effects, including anxiety, confusion, depression, dizziness, lactic acidosis

Antifungals

Some of the most common include: clotrimazole. econazole. miconazole. terbinafine. fluconazole. ketoconazole. amphotericin. Fungicide or fungistatic used to treat and prevent mycoses like athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and other fungal infections.

Tetracycline and doxycycline

Tetracycline Pharmacodynamics Bind reversibly to the 30S subunit of the bacterial ribosome Useful for gram positive, gram negative & intracellular organisms Pharmacokinetics Food decreases absorption: doxycycline least affected. Milk and calcium decrease absorption; doxycycline least affected Precautions and contraindications Tetracyclines are Pregnancy Category X except doxycycline (Pregnancy Cat D) Do not prescribe to pregnant women, lactating women, or children less than age 8 years (due to bone/teeth effects). Drug interactions: many, but most impacted by antacids & supplements Tetracyclines when used in children < 8 years of age can adversely impact bone growth Minocycline is a popular acne med in the tetracycline family. It has been associated with pseudotremor cerebri (idiopathic intracranial hypertension). Pt would c/o headache, blurred vision while taking minocycline. So, if pt c/o headaches while taking the med, should evaluate for this condition to protect against vision loss. Rare but notable ADR Clinical use and dosing Doxycycline is considered first-line therapy for C. trachomatis and Ureaplasma urealyticum. Tetracycline and minocycline are used to treat P. acnes. Some H. pylori regimens include tetracycline. Check hepatic function for long term use or for any IV use. Rational drug selection Doxycycline and minocycline can be taken with food. Patient education Administration, ADRs, avoid pregnancy, never use past expiration date Doxycycline is considered first-line therapy for C. trachomatis (known as an STI-Chlamydia infection) Ureaplasma urealyticum causes infections of the genitourinary tract, particularly urethritis; thought to be sexually transmitted and transmitted from mother to infant. It is a species that has been isolated from the respiratory tract and central nervous system of newborns. Doxycycline is known to cause photosensitivity. If treating chlamydia in woman of child-bearing age taking oral contraceptives, instruct to use a back-up method of birth control until her next menses. Instruct Pt to never use past expiration date as may cause toxicity