Woo Chapter 23- Drugs used to treat bacterial infections

Penicillinase-resistant penicillins activity

Chemical modifications of penicillin yield at this class of antibiotics that is stable in the presence of penicillinase produced by staphylococci

Cephalosporins

Beta-lactam Antibiotics, related to the penicillins. The class is divided into five generations.

Why is Age important when using penicillins?

Because most penicillins are really eliminated. Neonates and older adults often have poor renal function and are more prone to drug toxicity.

Penicillin V brand names

Beepen-VK, betapen-VK, ledercillin-VK, pen vee K, Veetids, V-cillin K

Ampicillin can interact with:

Beta blockers(Select a different penicillin if patient is taking atenolol), allopurinol (avoid coadministration)

Penicillin G benzathine brand name

Bicillin L-A

Penicillin G benzathine and propane combined brand name

Bicillin-CR

Third generation cephalosporins have enhanced

Beta- Lactamase resistance and extended gram-negative spectrum. They are good for infections where the resistance is a major consideration, like gonorrhea or resistant otitis media

Penicillins and adverse drug reactions

Type One hypersensitivity reactions have occurred, with an incidence of 0.015% to 0.04%. Some patients may have a pruritic maculopapular rash. Common reactions are nausea, vomiting, diarrhea, and epigastric distress. Should be taken with food.

Ampicillin/Sulbactam brand name

Unasyn

Piperacillin indications:

Uncomplicated urinary tract infection

Absorption and distribution of cephalosporins

Well absorbed from the G.I. tract, absorption is delayed by food. They are widely distributed to most tissues and fluids, penetration of CSF varies by generation. High concentrations of these drugs are found in bile

How do penicillins hinder bacterial growth?

by inhibiting the biosynthesis of bacterial cell wall mucopeptide (also called murein or peptidoglycan). This action is dependent on the drug reaching the penicillin - finding proteins (PBPs)

First generation cephalosporins

cefazolin, cephalexin, cefadroxil. Active against gram-positive cocci, including staph aureus and staph epidermidis

Third generation cephalosporins

ceftriaxone, cefotaxime, ceftazidime, cefdinir, cefpodoxime, cefixime, ceftibuten. They have activity against streptococcal species

Penicillin G and procaine indications:

neurosyphilis, congenital syphilis, diphtheria, rat bite fever

Antibiotics that contsin the Beta-lactam ring

penicillins, cephalosporins, carbapenems, and monobactams

Penicillin G and benzathine indications:

Prophylaxis for streptococcal infections in patient with rheumatic fever history, pharyngitis from Group A streptococci, syphilis

Alexander Fleming discovered penicillin in

1928

Penicillins are characterized by:

6-aminopenicillanic acid joined to the beta lactam ring

Minimum inhibitory concentration (MIC)

A laboratory measure of the lowest concentration of a drug needed to kill a certain standardized amount of bacteria.

Sub classes of penicillin that can be given IM:

All sub classes have agents that can be given intramuscularly, penicillin G procaine and penicillin G benzathine formulations are labeled for deep intramuscular administration

Penicillins are bacteriocidal against sensitive organisms and are most effective during:

Active cellular multiplication

Natural penicillins are effective against:

Aerobic, Graham end positive organisms, including streptococcus species and Group a beta hemolytic streptococcus, some enterococcus strains, and some non-- penicillinase - producing staphylococci

Amoxicillin brand names

Amoxil,Trymox, Polymox, Wymox

What are aminopenicillins commonly combined with for greater efficacy?

Ampicillin and amoxicillin are commonly combined with beta - lactamase inhibitors clavulanic acid and sulbactam, respectively. The inhibitors Prevent the destruction of beta-lactam antibiotics by serving as a competitive inhibitor of beta-lactamase

Cefazolin brand name

Ancef, kefzol

Cefaclor, cefdinir, and cefpodoxime can interact with

Antacids(Separate administration by at least two hours)

Ampicillin and ampicillin /sulbactam indications

Antibacterial

Oxacillin indications:

Antibacterial

cephalexin indication

Antibacterial for mild, Moderate, or severe infections, endocarditis prophylaxis, strep pharyngitis, tonsillitis, cystitis

Inappropriate use of antibiotics:

Antibiotics for viral infections, inadequate dosing, excessive duration of therapy, and increased empirical use of broad-spectrum antibiotics when not required

Amoxicillin and potassium clavulanate brand name

Augmentin

Penicillins are pregnancy category:

B. They should be used only when clearly indicated. They are excreted in low concentrations in breastmilk and may cause a response in the nursing infant.

Most common infections treated with penicillins are:

Bacterial upper respiratory infections, pneumonia, sexually transmitted infections, urinary tract infections, and wound infections. They are also used for endocarditis prophylaxis, eradication of H pylori and gastritis, and Lyme disease

Oxacillin brand names

Bactocill, prostaphlin

cefaclor (indication)

Bacterial Infections, pharyngitis, pneumonia, skin infections, tonsillitis, or urinary tract infection, acute exacerbation of chronic bronchitis

Cefotetan indications

Bacterial infections, urinary tract infections

Cefaclor brand name

Ceclor

Second generation cephalosporins and cephamycins

Cefaclor, cefotetan, cefoxitin, cefprozil, cefuroxime, loracarbef. Active against gram-positive cocci just like the first generation, but with increased activity against H influenzae

Fourth generation cephalosporin

Cefepime (Maxipime) Has a broader spectrum of activity and is more resistant to beta lactamases that inactivate many third-generation agents. Active against gram-positive and gram-negative organisms

Cefotetan brand name

Cefotan

Cephamycins include

Cefotetan and cefoxitin (they are lumped in with the second generation cephalosporins). They have limited activity against anaerobes, as well as similar activity to the rest of the second generation cephalosporins

Fifth generation cephalosporin

Ceftaroline (Teflaro). Similar activity to ceftriaxone, but also has excellent activity against MRSA.

Cefprozil brand name

Cefzil

Penicillin-resistant strains are commonly also resistant to:

Cephalosporins, Macrolides, and sulfonamides, and to a lesser extent, clindamycin. For that reason, they are commonly called drug - resistant S. Pneumoniae

Penicillin G can interact with:

Colestipol, cholestyramine (separate doses. Give penicillin G 1 hour before or four hours after these medications)

The CDC core elements of outpatient antibiotic stewardship:

Commitment, action for policy and practice, tracking and reporting, and education and expertise

Anti-pseudomonal penicillins

Comprised of Piperacillin combined with a beta lactamase inhibitor, tazobactam. It has enhanced activity against gram-negative bacilli, and retains activity against ampicillin-sulbactam-susceptible organisms. Only available IV.

Penicillin V indications:

Continuous prophylaxis of streptococcal infection in patients with history of rheumatic heart disease, group a beta hemolytic strep pharyngitis

Nafcillin can interact with:

Cyclosporine(If they must be use concurrently, monitor cyclosporine levels more closely)

Dicloxacillin sodium brand names

Dynapen, dycill, pathocil

Penicillins and allergic reactions

Less then 10% of patients will have an allergic reaction, but penicillins are the most likely antibiotics to cause an allergic reaction

Commitment:

Demonstrate dedication to and accountability for optimizing antibiotic prescribing and patient safety

Penicillins can interact with:

Diuretics (watch K level), Methotrexate(avoid), oral contraceptives (?), probenecid (Monroe for penicillin toxicity), tetracyclines (Monitor for therapeutic efficacy), and warfarin (monitor INR closely)

Cefadroxil brand name

Duricef

Oral first generation cephalosporins are interchangeable in terms of

Efficacy and safety. They have a fairly narrow spectrum

Cefadroxil indications

Endocarditis Prophylaxis, pharyngitis, tonsillitis, impetigo, skin and soft tissue infection, urinary tract infection

cefazolin indications

Endocarditis prophylaxis, urinary tract infection, antibacterial from mild to moderate infections

Adverse drug reactions in cephalosporins

Erythema multiforme, other skin rashes, arthralgia, and fever possible. Possible induction of seizure activity, especially in renal impairment. Coagulation abnormalities. Hemolytic anemia. C diff.

Cefotetan can interact with

Ethanol(Avoid concurrent ingestion of alcohol), anticoagulants (select a different anabiotic class for patients on anticoagulants, if not possible, monitor PT more closely)

Amoxicillin indications:

Exacerbation of chronic bronchitis, acute otitis media, chlamydia, H pylori eradication in peptic ulcer disease, sinusitis, suspected resistance S pneumoniae, endocarditis prophylaxis, Lyme disease, uncomplicated urinary tract infections

Penicillin Metabolism

Excluding Nafcillin and oxacillin, penicillins undergo negligible metabolism and are excreted Primarily as unchanged drugs in the urine

Second generation oral cephalosporins are slightly less active against

Gram positive cocci them first generation

Cefpodoxime and cefuroxime can interact with

H2 blockers (Cefaclor does not appear to be affected and may be substituted if appropriate)

HIV patients and penicillins

HIV positive patients are more susceptible to hepatotoxicity resulting from dicloxacillin, nafcillin, and oxacillin.

Precautions and contraindications for cephalosporins

Hypersensitivity reactions May happen in a small percentage of patients. There is some cross sensitivity with penicillin, though low, cephalosporins are not recommended for those who have had an anaphylactic reaction to a penicillin. pregnancy category B. Need to renally dose.

Penicillin G benzathine and procaine combined indications:

Pneumococcal infections, excluding meningitis

Augmentin indications:

Pneumonia, Exacerbation of chronic bronchitis, acute otitis media and sinusitis, animal bites other than spider bites

Four steps of rational drug selection

Identifying A clinical diagnosis, obtain cultures or specimens, making the microbial diagnosis, and drug selection

Action for policy and practice:

Implement at least One policy or practice to improve antibiotic prescribing, assess whether it is working, and modify as needed

Metabolism and excretion of cephalosporins

In general, Hepatic metabolism is not significant for cephalosporins. Most cephalosporins are excreted via the kidney in varying degrees as unchanged drug

Resistance to penicillins is due to:

Inactivation by beta-lactamases, alteration in target PBP's on the bacterial cell wall, or alteration in the outer membrane of a cell wall that decreases permeability to the site of action

Factors contributing to antibiotic resistance:

Increased populations of immunocompromised patients, increased number and complexity of invasive procedures, increased survival of patients with chronic diseases, excessive and inappropriate use of antibiotics

Dicloxacillin sodium indications:

Infections in cystic fibrosis patients

Cefdinir Can be affected by

Iron supplements (separate administration by two hours)

Cephalexin brand name

Keflex, keftab

Broth Dilution Method

Method consists of inoculating the organism into a series of liquid media containing increasing concentrations of the antibiotic

Oral penicillin formulations are generally well absorbed from the G.I. tract, but use is limited to:

Mild to moderate infections because higher than recommended doses cause G.I. distress and diarrhea

Minimum bacteriocidal concentration

Minimum concentration of antibiotic that kills the bacteria

Tracking and reporting:

Monitor antibiotic prescribing practices and offer regular feedback to clinicians, or have clinicians self assess their antibiotic prescribing practices

Penicillinase - resistant penicillins

Nafcillin, Oxacillin, and dicloxacillin

Penicillin V and dicloxacillin should be taken:

On an empty stomach, one hour before a meal or two hours after

Ampicillin brand names

Polycillin, principen, totacillin

All cephalosporins can interact with

Probenecid(Avoid coadministration), loop diuretics (monitor renal function), warfarin (monitor I NR)

4 natural penicillins that are commercially available

Penicillin V(administered orally), procaine penicillin and benzathine penicillin (administered intramuscularly), and penicillin G (administered IV)

Penicillins that are given orally:

Penicillin V, dicloxacillin, and amoxicillin

Four penicillin sub classes:

Penicillinase-sensitive or natural penicillins, amino - penicillins, penicillinase - resistant or antistaphylococcal penicillins, and anti-pseudomonal or extended-spectrum penicillins

Importance of site of infection in penicillin dosing

Penicillins enter CSF poorly, so a CNS infection may require a different agent, higher doses, IV administration, or prolong therapy

PBPs (penicillin binding proteins)

Transpeptidase, Carboxypeptidase, and endopeptidase enzymes involved in the terminal stages of forming the cell

Cefprozil indications

Pharyngitis, Tonsillitis, sinusitis, acute pneumonia, skin infections, otitis media, urinary tract infection

Piperacillin brand name

Pipracil

Penicillins are bound to:

Plasma proteins to varying degrees and are well distributed to most tissues in body fluids

Education and expertise:

Provide educational resources to clinicians and patients on antibiotic prescribing, and ensure access to need an expertise on optimizing antibiotic prescribing

Cephalosporins are used for

Respiratory pathogens, Including acute otitis media, sinusitis, and group a streptococcal pharyngitis, pneumonia, chronic bronchitis, Urinary tract infections, ceftriaxone is used for gonorrhea.

Efficacy of an antibiotic is affected by:

The organism's susceptibility, dose, tissue concentration, and rate of organism multiplication

The extent of oral absorption of penicillins depends on:

The specific structure of the antibiotic, the pH of the stomach and intestine, and presence of food

Cephalosporins in pregnancy and children

They have a shorter half-life during pregnancy and increased clearance. In Neonates , immature renal function leads to accumulation of drugs and prolonged half lives.

Aminopenicillins

They have reliable activity against Graham - positive organisms, including streptococcus and enterococcus species. They have greater activity against Gram-negative bacteria because of their enhanced ability to penetrate the outer membrane of the organisms. ampicillin and amoxicillin are the only two available aminopenicillins

Spectrum of activity of cephalosporins

They inhibit mucopeptide synthesis in the bacterial cell wall, making the bacterium osmotically unstable. They are usually bactericidal