Pharmacology II Section 1

Tetracyclines Drug Interactions • _____ with divalent & trivalent ions Ca, Mg, Al, Fe, Zn, (i.e., ________________). • One ounce of antacid, a cup of milk, etc. will ______ ~50%. o Note: this interaction is even more significant with some of the fluoroquinolones.

Chelation antacids, dairy products & iron decreased absorption

Macrolide's (E, C, A) History • _____, the first macrolide antibiotic, has been used clinically since 1952, but is used less today since the introduction in the 1990s of azithromycin (Zithromax) and clarithromycin (Biaxin). Mechanism of Action • Macrolide antibiotics bind to the _____, inhibiting bacterial protein synthesis. • Activity of erythromycin against _____ organisms generally is greater than against gram-negative organisms. • The macrolides have good efficacy against mycoplasma, H. flu, (except for erythromycin) susceptible S. pneumoniae (Not MDRSP), group A strep and M. Catarrhalis

Erythromycin 50-S ribosomal subunit gram-positive

Cephalosporins Fourth Generation Agent Similar to third generation 1) __________ —dose must be adjusted in patients with _____ due to some reported cases of nonconvulsive ____ in patients with renal impairment who did not receive appropriate dosage adjustments of cefepime.

cefepime (Maxipime®) renal impairment status epilepticus

*Antibiotic Prescriptions for Kids Declined 14%* from 2002 to 2010 The number of antibiotics for children ____ in the last decade, but still _____ pediatric prescriptions are for antibiotics.

declined 4 of the top 5

Natural Penicillins • IM formulations of Penicillin G should be refrigerated, but can bring to room temperature prior to injection to ____. These products include: Pen. G and Pen. V made the cut, but Pen V is not stable without ____. o Penicillin G benzathine (Bicillin L-A®) o Penicillin G benzathine + penicillin G procaine (Bicillin C-R®) (Procaine is a local anesthetic.) o Penicillin G procaine (Wycillin®) ♣ Bicillin C-R® contains both Penicillin G benzathine and Penicillin G procaine. Wycillin® contains only Penicillin G procaine. Both are long-acting, but Penicillin G benzathine *(Bicillin L-A®) is the only product currently approved for the treatment of syphilis*. • *Bicillin L-A contains pen G benzathine which is ____ thus ____. • *Bicillin C-R®* is _____ pen G making it immediate-release and thus _____.

decrease pain Potassium Long Acting, effective for syphillis Combined with pRocaine, not effective for syphilis

Macrolide-like Agents Clindamycin (Cleocin®) ¬ Good for B. fragilis (anaerobe); can be combined with gentamicin. ¬ Notorious for causing ____ and _____ (PMC). ¬ Can use in ______ clients, especially in dental infections. ¬ Topical use for ____ (Cleocin-T®) solution and pledgets. ¬ Cleocin® and Clindesse® 2% cream available for _____. Similar to oral metronidazole (Flagyl®) for treating bacterial vaginosis.

diarrhea and pseudomembranous colitis penicillin-allergic acne bacterial vaginosis

Bioterrorism • ____ has received most of the publicity. o Early signs of anthrax are similar to ____; rhinitis may often not be present. o *If suspected, don't wait for test results*—treat with ____: Amoxicillin 80 mg/kg/day in three doses should be used for young children and pregnant women, although for serious cases, many will use fluoroquinolones, e.g., Cipro® even in pregnancy. o The normal adult dose is ciprofloxacin p.o. 500 mg or I.V. 400 mg every 12 hours +doxycycline 100 mg every 12 hours, or one or two additional antibiotics. o Duration of therapy is dependent on clinical outcome, but CDC recommends *continuing for at least* _____.

*Anthrax* influenza antibiotics 60 days

Macrolide Agents Azithromycin (Zithromax®, Z-Pak) ¬ Originally and still commonly used in the "Z-PAK®" dosed 2 doses STAT, then qd for 4 days. Also approved in _____ regimens. ¬ Can be used for chlamydia in_____ since doxycycline and quinolones are contraindicated. ¬ Does _____ affect cytochrome P-450, so less drug interactions than erythromycin. ¬ It causes ____ gastrointestinal adverse reactions than erythromycin. ¬ _____ effects: Some studies suggest a link, whereas others do not: o May 2012 NEJM article reported on an observational study conducted at Vanderbilt on a TennCare cohort in which patients taking azithromycin had a *small increased risk for sudden cardiac death* compared with patients taking amoxicillin, ciprofloxacin, or no antibiotic at all. o A large European study reported in the April 18, 2017 issue of the Canadian Medical Association Journal (CMAJ) suggest that the risk of ventricular arrhythmia with azithromycin use is likely to be *mainly due to the poor state of health of the patient due to the underlying infection rather than due to the drug itself*. ¬ Resistance has been reported.

*single-dose* pregnancy not fewer Cardiac

Do You Really Need An Antibiotic for URIs? • Now you can use real numbers to explain how *risks outweigh benefits* when taking antibiotics for most acute respiratory infections. o There's only a ____ chance that an antibiotic will help most acute upper respiratory infections. But there's a 1 in 4 chance of _____...a 1 in 50 chance of a ____...and a 1 in 1000 chance it'll cause an ____.

1 in 4000 diarrhea skin reaction ER visit

Antibiotic Prophylaxis and Postoperative Infections The Medical Letter, May 23, 2016 • TIMING AND DURATION — Administration of the prophylactic antibiotic should begin within ______ to ensure adequate serum and tissue levels. If vancomycin or a fluoroquinolone is used, the infusion should be started within 60-120 minutes before the initial incision because of the prolonged infusion times required for these drugs. • A ____ prophylactic dose of an antimicrobial is usually sufficient for most procedures; continuation of prophylaxis for >24 hours after the procedure is not recommended. If you use, it has to be started 1-2 hours PRIOR to 1st incision, and is usually just one dose

60 minutes before the initial surgical incision single

• Compared with staph,_____ is relatively new, but in many hospitals now *surpasses MRSA as the most frequent nosocomial infection*. o It was first diagnosed in 1978, when it appeared as an occasional cause of *diarrhea* in patients who were taking ____. o Today, virtually any antibiotic can trigger the problem. o It occurs in hundreds of thousands of people in the U.S. each year, even some who haven't taken antibiotics. o Many healthy people harbor a few C.diff among the millions of bacteria in the colon. C.diff is harmless, but if _____.

Clostridium difficile (C.diff) clindamycin (Cleocin®) antibiotic therapy knocks off the normal bacteria, C.diff grows, producing two toxins that attack the colon. (superinfection)

Amino glycosides Side/Toxic Effects The two most notorious side or toxic effects of the aminoglycosides are: ¬ _____ (vestibular and 8th nerve damage causing ataxia and hearing loss) occurs in 10% to 12% of patients, resulting in permanent cochlear and vestibular damage. ¬ ______ o When administered for more than just a few days, must monitor _____ and/or aminoglycoside blood levels and adjust dose accordingly. o First indications of aminoglycoside renal toxicity may be _______, reflecting decreasing renal drug clearance. o Nephrotoxicity is in the 0-50% range, with 10-25% reported in most trials. Some consider it a major issue, while others say it is almost non-existent unless other nephrotoxic drugs are concurrently prescribed. The incidence of nephrotoxicity associated with aminoglycosides is increased with the concurrent administration of _____. ¬ As a nurse or a practitioner, you should be aware of the need for ____ and ____.

Ototoxicity Nephrotoxicity (kidney) renal function increased "trough" drug concentrations vancomycin monitoring renal function and drawing blood for peak and/or trough levels.

Tetracyclines Adverse Reactions and Contraindications • ______—avoid sunlight and take at ______ if once-a-day therapy • Traditionally, all tetracyclines have been contraindicated in ________ and _____ due to _____ and _____. o However, a recent study in Journal of Pediatrics, March 17, 2015 examined the effect of doxycycline on the teeth of children being treated for suspected Rocky Mountain spotted fever (RMSF). The study, led by CDC and Indian Health Service researchers, included 58 children who received an average of 1.8 courses of doxycycline before age 8 years. Dentists observed no tetracycline-like staining in any of the exposed children's teeth, and they noted no significant difference in tooth shade or hypoplasia between these children and a group of 213 children who had never received doxycycline. The researchers suggest that modifying the drug's label could help to increase health care provider confidence in use of doxycycline for suspected RMSF in children. *So if RMSF, children can take doxycline with no teeth staining*

Photosensitivity- bedtime pregnancy and children stained teeth of baby and stunted growth.

Tetracyclines Mechanism of Action Work by inhibition of protein synthesis at the level of the binding of transfer ____, providing a ____.

RNA bacteriostatic effect

What Are the Solutions for Antibiotic Resistance? • Practice Antibiotic Stewardship o ____ courses of antibiotics are virtually always effective in well-controlled trials. The traditional myth: To Prevent Resistance, Patients Must ______, is *outdated*. Despite how widespread and deeply this belief is held, there are *no data* to support the idea that ______. o According to Spellberg B. The new antibiotic mantra—"_______." JAMA Intern studies have repeatedly found that shorter-course therapies are *less likely to select out for antibiotic resistance*, which is consistent with fundamental principles of natural selection. *Use for as few days as possible.*

Short Complete Every Dose of Antibiotics Prescribed, Even After They Feel Better continuing antibiotics past resolution of signs and symptoms of infection reduces the emergence of antibiotic resistance shorter is better

• The word "antibiotic" has always been a symbol of the miracles of modern medicine. Perhaps they're a bit ordinary these days compared with robotic surgery or capsule endoscopy, but in a different time, antibiotics literally changed the world. • It began in 1928 when bacteriologist Alexander Fleming serendipitously realized that the growth of _____ was inhibited in a petri dish contaminated by ___.

Streptococcus aureus mold

• Surprisingly, ______ have never fully developed resistance to penicillin and it remains a reasonable choice antibiotic for many types of streptococcal infections. o _______ are inherently resistant to penicillin because their vulnerable _____ that prevents permeation of the penicillin molecule. • As if there were not already enough to worry about, in the early days of the 21st century, severe acute respiratory syndrome (SARS), vancomycin-resistant Staphylococcus aureus (VRSA), and H1N1 are causing concern and consternation among public health officials and the public.

Streptococcus pyogenes (Group A strep) Gram-negative bacteria cell wall is protected by an outer membrane

• Unfortunately, while scientists were discovering new antimicrobial agents, we never developed the _______. • Instead, _____ became the vehicles of long-term innocent misuse of these live-saving drugs. • But we underestimated the selective pressure that antibiotics were capable of exerting on bacteria. • Within a few decades, it became clear that the overuse of antibiotics was fueling the natural evolution of the microbes we were trying to kill, encouraging them to develop _____.

ability to swiftly identify an infectious agent, which might have permitted more targeted antibiotic therapy broad-spectrum antibiotics resistance as rapidly as they were able

Macrolide Agents Erythromycin ¬ Erythromycin is notorious for causing _____. ¬ It is a P-450 (CYP) _____ and will increase levels of many drugs.

adverse GI effects. enzyme inhibitor

Superbug Has Reached the U.S. U.S. researchers reported May 26, 2016 that a woman in Pennsylvania was recently found to have bacteria resistant to _____. She had a strain of *E. coli* that is resistant to ____. In the report, the researchers wrote that the finding "heralds the emergence of a truly pan-drug resistant bacteria." _____ *is used as an antibiotic of last resort for especially dangerous types of superbugs, including a family of bacteria called carbapenem-resistant enterobacteriaceae (CRE)*. This is the first instance in which this colistin-resistant strain has been found in a patient in the U.S. "It basically shows us that the end of the road isn't very far away for antibiotics—that we may be in a situation where we have patients in our intensive-care units, or patients getting urinary tract infections for which we do not have antibiotics," CDC Director Tom Frieden stated.

antibiotics of last resort. colistin Colistin

Monobactams The only one currently available is ______ and it is available only in a parenteral formulation. Used only for ____ infections, including P. aeruginosa, or if client is _____. ¬ Good stability against ____ enzymes. ¬ Comparable to aminoglycosides in Gm (-) pneumonia and UTI. It has no ____ activity. ¬ Safe in penicillin-allergic clients.

aztreonam (Azactam®) Gm (-) allergic to penicillin (not Beta lactames) beta-lactamase Gm (+)

Beta-Lactam Antibiotics Penicillins, Carbapenems, Cephalosporins • Mechanism of action is_____ by interference with the biosynthesis of bacterial cell wall. • Following is the chemical structure of the beta-lactam structure with the arrows showing the acid-sensitive bond and site of beta-lactamase ("penicillinase") attack that destroys the integrity of the molecule, rendering it ineffective against _____. See flashcard.. *Approaches to the Beta Lactase Production* • _____ can be added to ß-lactam antibiotics to "protect" against cleavage of the beta-lactam ring by____. • Clinically and microbiologically, this *expands* the bacteriocidal spectrum of the beta-lactam antibiotic to include those organisms that produce _____. • β-lactamase inhibitors include: ⎫ Clavulanate (in Augmentin®) ⎫ Tazobactam (in Zosyn®) ⎫ Sulbactam (in Unasyn) ⎫ Avibactam (in Avycaz®)

bactericidal bacteria that release beta-lactamase *Beta-lactamase inhibitors* ß-lactamase ß-lactamase

Aminoglycosides ¬ Mechanism of action: it is not clear how aminoglycosides cause bacterial cell death. It is known that aminoglycosides _____ subunit, subsequently ______. They have good activity against severe infection by ____ aerobic bacteria (e.g., E. Coli, Klebsiella, Proteus, and Pseudomonas). Agents 1) gentamicin (Garamycin®)—can be combined with ____ injection ("amp/gent"). 2) kanamycin (Kantrex®) 3) neomycin (Mycifradin®)—not absorbed _____, topical use and gut sterilization. 4) streptomycin—primary use in ____. 5) netilmicin (Netromycin®) 6) amikacin (Amikin®) 7) tobramycin (Nebcin®)—also available for cystic fibrosis as TOBI® Podhaler (tobramycin inhalation powder)

bind irreversibly the 30-S ribosomal inhibiting bacterial protein synthesis Gm (-) ampicillin systemically TB.

"Superinfection" or Secondary Infection When a _____ antibiotic eradicates most normal bacterial flora, the _____ are left with excess nutrients and tend to "overgrow" leading to a "superimposed" infection. The three most common are: ⎫ Vaginal candidiasis or ____ infection ⎫ Oral candidiasis or ____ ⎫ Diarrhea leading to pseudomembranous colitis (PMC) due to overgrowth of _____ infections (CDI). One infection on top of another. Antibiotic decreases the bacteria, there are more available nutrients, yeast grows, now we need anti fungal. (bacterial, yeast, fungal)

broad spectrum non-susceptible organisms "Yeast" "Thrush" clostridium difficile ("c. dif")

Carbapenems Carbapenems are ____ IV antibiotics that cover many *gram-positive and gram negative organisms* and anaerobes. Generally reserved for ____ such as pseudomonas and hospital-acquired pneumonia. (Still b-lactam drugs) All have a _____ in penicillin allergic clients. However, results of a study published online November 22, 2014 in the Journal of Allergy and Clinical Immunology suggests that patients who are allergic to penicillin can tolerate carbapenems. However, the lead author stated "In those who especially require these alternative beta-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability."

broad-spectrum "bad" organisms possible cross-reaction

Cephalosporins Fifth Generation Agents 1) ______—approved 2010 for MRSA,. Medical Letter, January 24, 2011 states: "Ceftaroline (Teflaro®) is the first beta-lactam antibiotic with activity against _____. It has been effective for treatment of skin and skin structure infections, including those caused by MRSA, but some patients with complicated infections were excluded from clinical trials. Whether it is effective for treatment of other MRSA infections, including pneumonia, remains to be established." 2) 2014 approval of _____ (ceftolozane/tazobactam), I.V. drug to treat adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). The drug combines the cephalosporin ceftolozane with the beta-lactamase inhibitor tazobactam. Cost is $5000 - $6000.

ceftaroline (Teflaro®) MRSA Zerbaxa®

*CDC Warns that Gonorrhea is on the Verge of Being Untreatable* Data analyzed from the Gonococcal Isolate Surveillance Project and city-level gonorrhea incidence rates from surveillance data for 17 cities during 1991-2006 found a *strong likelihood of future increases in gonorrhea incidence caused by emerging* ______. *WHO Warns of a Post-Antibiotic Era Where Common Infections Kill* • In 2014, the World Health Organization (WHO) warned that a ______ in which common infections and minor injuries lead to death is a real possibility this century.

cephalosporin resistance post-antibiotic era

Tetracyclines Agents 1) tetracycline hydrochloride (generic only) 2) doxycycline (Vibramycin®, Oracea® for rosacea) • Most _____ tetracycline. • _____ with antacids and food. • Widely used for "routine" infections, also good for chlamydia, anthrax, Rocky Mountain Spotted Fever (Rickettsia rickettsii) and malaria. 3) minocycline (Minocin®) 4) oxytetracycline (Urobiotic®, Terramycin®) 5) demeclocycline (Declomycin®)—notoriously phototoxic

commonly used Less chelation

What Are the Solutions for Antibiotic Resistance? • Reduce Inappropriate Antibiotic Use in Outpatients o The abuse of antibiotics is well known and in large part reflects ____ because the patient expects to walk out of the clinic with a prescription for that viral respiratory tract infection. o The "3-day prescription," "Delay Fill," "Watchful Waiting," or "Wait and See Prescription" (WASP) are effective means to limit antibiotic utilization. According to American Family Physician, July 15, 2014, delayed prescription strategies resulted in fewer than 40% of patients receiving antibiotics. ♣ According to the December 21, 2015 issue of JAMA Internal Medicine, for adults with uncomplicated respiratory tract infections, delayed prescription strategies are associated with reduced antibiotic use compared with immediate prescriptions.

consumer demand

*Antibiotic Resistance: A Crisis* • Antibiotic resistance has been declared a ____ by the World Health Organization, the Centers for Disease Control and Prevention (CDC), the Institute of Medicine, the Infectious Diseases Society of America, and virtually all other relevant organizations. • Contributing to this crisis are the following facts: o Pharmaceutical companies are _____ because they "can't break even." The last new antibiotic class for gram-negative bacteria was the _____, developed 4 decades ago. o ______ in the United States is widespread. We have only 4.6% of the global population but we have 46% of the global antibiotic market. o Our _____ record is dismal. A patient entering a US hospital is 40 times more likely to acquire MRSA bacteremia than a patient entering a hospital in The Netherlands.

crisis no longer developing new antibiotics quinolone Antibiotic abuse prevention

What Are the Solutions for Antibiotic Resistance? • Stop Antibiotic Use on the Farm o A full 80% of antibiotic use in the U.S. is for growth promotion and disease prevention in _____. Resistant bacteria and resistance genes can be traced from the ____ to ____ and, finally, to blood cultures in patients (The "farm to fork" phenomenon). = bacterspecima ♣ *The American Medical Association* is opposed to this practice. = They say if 1 cow gets sick, they then pass it to the entire herd, and we have no food and starve

farm animals chickens to the chicken meat in grocery stores

Cephalosporins *Third Generation Oral* Agents Good ____ coverage in ____, but does not cover ____ gram-negatives such as ____ or ____. 1. cefixime (Suprax®) 2. ceftibuten (Cedax®) 3. cefdinir (Omnicef®)—widely used in pediatrics and is considered by some to be the drug of choice for children with penicillin allergies. 4. cefditoren (Spectracef®)

gram-negative outpatients inpatient Enterobacter or Pseudomonas aeruginosa.

Cephalosporins Second Generation Agents Somewhat enhanced activity against ____ organisms, but much less than third generation agents. Good coverage for ___ and ____. Clinically effective for many cases of otitis media, lower respiratory tract infections, including pneumonia, pharyngitis, and tonsillitis, UTIs, and skin and soft tissue infections. 1) cefaclor (Ceclor®) 2) cefamandole (Mandol®) 3) cefoxitin (Mefoxin®) 4) cefuroxime (Zinacef®) 5) cefotetan (Cefotan®) 6) cefprozil (Cefzil®) 7) cefpodoxime (Vantin®)

gram-negative Strep pneumoniae and H. influenzae

Cephalosporins Third Generation Parenteral Agents Less active than first generation agents against____, but much more active against _____, including those that produce ß-lactamase. 1) cefotaxime (Claforan®) 2) cefoperazone (Cefobid®) 3) ceftizoxime (Cefizox®) 4) ceftazidime (Fortaz®, Tazidime®, Tazicef®, Ceptaz®) 2015 approval of ceftazidime combined with a new beta-lactamase inhibitor avibactam (Avycaz®) for the treatment of adults with complicated intra-abdominal infections, in combination with metronidazole, and complicated UTIs. 5) ceftriaxone (Rocephin®)

gram-positive cocci Enterobacteriaceae

Cephalosporins Summary of Generations of Cephalosporins First Generation Agents Most _____ are susceptible (except enterococci and MRSA); less activity against ____ organisms. Good for outpatient skin infections and good activity against non-methicillin resistant staph and oral cavity anaerobes, Moraxella catarrhalis, E. coli, K. pneumoniae and Proteus mirabilis. 1) cephalexin (Keflex®)—Effective for MSSA skin and soft tissue infections 2) cefadroxil (Duricef®) 3) cefazolin (Ancef®, Kefzol®) 4) cephradine (Velosef)

gram-positive cocci gram-negative

Macrolide Agents Clarithromycin (Biaxin®, Biaxin XL®) ¬ Biaxin XL is 500 mg tablet for once-a-day dosing and is ____ to cause GI upset than erythromycin, but does cause _____ ("bad taste" in the mouth). ¬ Some of the same ____ as erythromycin since it is a CYP3A4 inhibitor. o A warning from the FDA states that "serious adverse reactions have been reported in patients taking clarithromycin concomitantly with CYP3A4 substrates, which includes hypotension with calcium-channel blockers metabolized by CYP3A4 (such as verapamil, amlodipine, diltiazem)." ¬ Suspension available, but do not refrigerate—keep at room temperature. ¬ Has been associated with cardiac arrhythmias.

less likely *dysgeusia* drug interactions

Minimum Inhibitory Concentration • The minimum inhibitory concentration (MIC) is the _____ that prevented visible growth of an organism after 24 hours of incubation in a specified growth medium. Lowest concentration of an antibiotic that it takes to inhibit growth (zone of inhibition)

lowest antimicrobial concentration

Intravenous Extended Spectrum (or Antipseudomonal) Penicillins 1) ticarcillin (Ticar®) 2) piperacillin (Pipracil®) 3) piperacillin/tazobactam (Zosyn®) 4) mezlocillin (Mezlin®) *Antistaphylococcal Penicillins or "Penicillinase-Resistant" Penicillins* In response to a growing problem of staph resistance, in 1959, *methicillin*, the first "penicillinase" proof antibiotic, was developed. However, in the early 1960s, methicillin-resistance staph aureus (MRSA) began to crop up in hospitals. It now constitutes the majority of strains in some hospitals and has also exploded in the community. In the strains that are ______ or Non-MRSA "staph" these agents may be effective. These work on MSSA, but not MRSA. 1) cloxacillin (Tegopen) 2) dicloxacillin (Dynapen) 3) nafcillin (Unipen®) 4) methicillin (Staphcillin®)—not used clinically today; only use is to classify bacteria, e.g., MRSA.

methicillin sensitive staph aureus (MSSA)

Clarification and Classification of "Penicillin" Allergy • Penicillin "allergy" history is self-reported by about 1 out of 10 persons. Of 30 million US patients thought to be penicillin-allergic, an estimated 28.5 million actually are ___, meaning that up to ____ patients who think they are allergic to penicillin are misinformed. Details on previous reactions to penicillin will distinguish those who experienced classic "type I" manifestations of serious allergy (e.g., anaphylaxis, closing of throat) from patients who have experienced a ____ reaction to the agent (e.g., GI upset, headache, or rash). • According to the CDC, approximately ___% of patients with IgE-mediated penicillin allergy lose their sensitivity after _____. So, only 19 out of 20 people that think they have it don't. and of those people, 80% of them lose it after 10 years. • The following questions are recommended to clarify the reaction: ⎫ What was the patient's age at the time of the reaction? ⎫ What were the characteristics of the reaction? ⎫ How long after beginning penicillin therapy did the reaction begin? ⎫ What other medications was the patient taking and at what time? ⎫ Has the patient taken any antibiotics similar to penicillin (i.e., amoxicillin, ampicillin, or cephalosporins) and, if so, what were the reactions?

not 19 of 20 nonallergic 80% 10 years.

Carbapenems -PENEM 1) imipenem/cilastatin (Primaxin®) • A broad spectrum antibiotic that contains cilastatin, which inhibits renal dipeptidase that breaks down imipenem. 2) meropenem (Merrem®) • Probably more effective than Primaxin for some aerobic Gram-negative infections, e.g., intra-abdominal infection in adults and bacterial meningitis in children. 3) ertapenem (Invanz®) • Invanz® is used in hospitals for complicated intra-abdominal, skin, and skin structure infections. Unlike other carbapenems, it does ______. • Considered equivalent to Rocephin® (ceftriaxone) or Zosyn® (piperacillin/tazobactam). 4) doripenem (Doribax®) • It has demonstrated activity against a wide range of Gram-positive and Gram-negative bacteria, including Pseudomonas. • In 2014, the FDA added a warning of mortality risk and poorer clinical cure rate when used to treat pneumonia that develops on mechanical ventilation.

not cover certain hospital-acquired pathogens such as Pseudomonas and Acinetobacter

• The first antibiotic, ____, was discovered in 1929 by Sir Alexander Fleming who observed inhibition of staphylococci on an agar plate contaminated by a Penicillium mold. _____ (and the inevitable bacterial infections that occurred in war-related wounds) was an important impetus to study the chemotherapeutic value of penicillin. Dr. Florey further explored and produced penicillin as it became generally available for treatment of bacterial infections, especially those caused by staphylococci and streptococci, in about 1946. Initially, the antibiotic was effective against *all sorts of infections* caused by these two _____ bacteria. • Resistance to penicillin in some strains of staphylococci was recognized ____ after introduction of the drug. Resistance to penicillin today occurs in almost all strains of Staphylococcus aureus. _____ has become one of the most fervent medical and public health problems.

penicillin World War II Gram-positive almost immediately Methicillin-resistant S. aureus (MRSA)

Cephalosporins ¬ Same mechanism of action as ____ (beta-lactams) with similar adverse ____ effects, e.g., diarrhea, N & V as the other β-lactams and also _____ from I.V. injections. ¬ Possible cross-sensitivity in "penicillin-allergic" clients, but recent data suggests it's much less than originally thought. It is most likely related to the ___ that some beta-lactams share rather than the beta-lactam ring. Only about 2% of clients with a positive penicillin skin test react to a cephalosporin, and this decreases to 0.1% if the initial penicillin reaction was mild. o Not absolutely contraindicated, but use with caution, particularly the first and second-generation agents. Much less likely with ____ generation agents.

penicillins GI thrombophlebitis side chain 3rd

Antibiotic Prophylaxis and Postoperative Infections • Antimicrobial prophylaxis for surgery should be directed against _____, but it does not need to eradicate every potential pathogen to be effective. _____, a first-generation cephalosporin active against many staphylococci and streptococci, can be used for most procedures. • In patients who are colonized with *MRSA* or in institutions where surgical site infections are frequently due to methicillin-resistant staphylococci, _____ could be considered for prophylaxis; it should be given in addition to the routine prophylactic regimen recommended for the procedure. Vancomycin is less effective than cefazolin for prevention of infections due to MSSA, it has a long infusion time, and regular use possibly could lead to emergence of VRE. • Preoperative identification of patients who are *nasal carriers of MRSA or MSSA* and decolonization using intranasal ____ (Bactroban Nasal®) and chlorhexidine (Peridex®) have been shown to decrease surgical site infections following some procedures (primarily cardiac and orthopedic), but resistance to mupirocin could emerge if it is used routinely.

the most likely infecting organisms *Cefazolin (Ancef®)* *vancomycin (Vancocin®)* mupirocin

Infections as a Cause of Chronic Disease There is some evidence that *infections and inflammation* might play a significant role in some chronic diseases. This concept gained momentum a few years ago when the link between ___ and ___ was discovered. Other examples of a possible link include Irritable bowel syndrome (IBS) may be linked to bacterial overgrowth in the small intestines and autoimmune disorders such rheumatoid arthritis (RA), Crohn's disease and multiple sclerosis may have a *bacterial component*. For example, we've long known that ____ seem to improve symptoms of RA. Antibiotics can help things such as asthma and RA, chronic issues

ulcer disease and H. pylori tetracyclines

What Are the Solutions for Antibiotic Resistance?

• Stop Antibiotic Use on the Farm • Practice Antibiotic Stewardship • Reduce Inappropriate Antibiotic Use in Outpatients • Adopt Rapid Diagnostic Tests • Develop New Drugs