Chapter 127. Treatment and Prophylaxis of Bacterial Infections (Part 13) pot

Treatment and Prophylaxis of Bacterial Infections Part 13 Macrolides and Ketolides Erythromycin, clarithromycin, and telithromycin inhibit CYP3A4, the hepatic P450 enzyme that metabol

Chapter 127 Treatment and Prophylaxis

of Bacterial Infections

(Part 13)

Macrolides and Ketolides

Erythromycin, clarithromycin, and telithromycin inhibit CYP3A4, the hepatic P450 enzyme that metabolizes many drugs, including cyclosporine, certain statins (lovastatin, simvastatin), theophylline, carbamazepine, warfarin, certain antineoplastic agents (e.g., vincristine, irinotecan), and ergot alkaloids In ~10% of patients receiving digoxin, concentrations increase significantly when erythromycin or telithromycin is coadministered, and this increase may lead to digoxin toxicity Azithromycin has little effect on the metabolism of other drugs Many drugs (e.g., azole antifungal drugs, diltiazem, verapamil, and nefazodone) can also increase absorption or inhibit erythromycin metabolism These effects are associated with prolongation of the QT interval and a fivefold increase in mortality rate This example serves as a reminder that the true significance of drug-drug

interactions may be subtle yet profound and that close attention to the evolving safety literature is important

Quinupristin/Dalfopristin

Quinupristin/dalfopristin is an inhibitor of CYP3A4 Its interactions with other drugs should be similar to those of erythromycin

Linezolid

Linezolid is a monoamine oxidase inhibitor Its concomitant administration with sympathomimetics (e.g., phenylpropanolamine) and with foods with high concentrations of tyramine should be avoided Many case reports describe serotonin syndrome following coadministration of linezolid with selective serotonin reuptake inhibitors

Tetracyclines

The most important interaction involving tetracyclines is reduced absorption when these drugs are coadministered with divalent and trivalent cations, such as antacids, iron compounds, or dairy products Food also adversely affects absorption of most tetracyclines Inducers of hepatic isoenzymes, such as phenytoin and rifampin, increase the clearance of doxycycline; although the clinical significance of this effect is unknown, use of an alternative antibiotic may

be appropriate

Sulfonamides

Sulfonamides, including TMP-SMX, increase the hypoprothrombinemic effect of warfarin by inhibition of its metabolism or by protein-binding displacement

Fluoroquinolones

There are two clinically important drug interactions involving fluoroquinolones First, like tetracyclines, all fluoroquinolones are chelated by divalent and trivalent cations, with a consequential significant reduction in absorption Second, ciprofloxacin inhibits the hepatic enzyme that metabolizes theophylline Scattered case reports suggest that quinolones can also potentiate the effects of warfarin, but this effect has not been observed in most controlled trials

Rifampin

Rifampin is an excellent inducer of many cytochrome P450 enzymes and increases the hepatic clearance of a large number of drugs, including the following (with the indicated predictable outcomes): HIV-1 protease inhibitors (loss of viral suppression), oral contraceptives (pregnancy), warfarin (decreased prothrombin times), cyclosporine and prednisone (organ rejection or exacerbations of any underlying inflammatory condition), and verapamil and diltiazem (increased

dosage requirements) Before rifampin is prescribed for any patient, a review of concomitant drug therapy is essential

Metronidazole

Metronidazole can cause a disulfiram-like syndrome when alcohol is ingested Thus, patients taking metronidazole should be instructed to avoid alcohol Inhibition of the metabolism of warfarin by metronidazole leads to significant rises in prothrombin times

Prophylaxis of Bacterial Infections

Antibacterial agents are occasionally indicated for use in patients who have

no evidence of infection but who have been or are expected to be exposed to bacterial pathogens under circumstances that constitute a major risk of infection The basic tenets of antimicrobial prophylaxis are as follows: (1) The risk or potential severity of infection should outweigh the risk of side effects from the antibacterial agent (2) The antibacterial agent should be given for the shortest period necessary to prevent target infections (3) The antibacterial agent should be given before the expected period of risk (e.g., within 1 h of incision before elective surgery) or as soon as possible after contact with an infected individual (e.g., prophylaxis for meningococcal meningitis)

Table 127-9 lists the major indications for antibacterial prophylaxis in adults The table includes only those indications that are widely accepted, supported by well-designed studies, or recommended by expert panels Prophylaxis is also used but is less widely accepted for recurrent cellulitis in conjunction with lymphedema, recurrent pneumococcal meningitis in conjunction with deficiencies in humoral immunity or CSF leaks, traveler's diarrhea, gram-negative sepsis in conjunction with neutropenia, and spontaneous bacterial peritonitis in conjunction with ascites The use of antibacterial agents in children

to prevent rheumatic fever and otitis media under certain circumstances is also common practice

Table 127-9 Prophylaxis of Bacterial Infections in Adults

Durationof Prophylaxis

Cardiac lesions

susceptible to bacterial

Amoxicillina Before and

after procedures

endocarditis causing

bacteremia

Recurrent S aureus

infections

Mupirocin 5 days

(intranasal)

Contact with patient

with meningococcal

meningitis

Rifampin Fluoroquinolone

2 days Single dose

Bite woundsb Penicillin V or

amoxicillin/clavulanic acid

3–5 days

Recurrent cystitis

Trimethoprim-sulfamethoxazole or a fluoroquinolone or nitrofurantoin

3 times per week for up to 1 year or after sexual intercourse

Clean (cardiac, Cefazolin (vancomycin)c Before and

vascular, neurologic, or

orthopedic surgery)

during procedure

Ocular Topical combinations and

subconjunctival cefazolin

During and

at end of procedure

Clean-contaminated

(head and neck, high-risk

gastroduodenal or biliary

tract surgery; high-risk

cesarean section;

hysterectomy)

Cefazolin (or clindamycin for head and neck)

Before and during procedure

Clean-contaminated

(vaginal or abdominal

hysterectomy)

Cefazolin or cefoxitin or cefotetan

Before and during procedure

Clean-contaminated

(high-risk genitourinary

surgery)

Fluoroquinolone Before and

during procedure

Clean-contaminated

(colorectal surgery or

appendectomy)

Cefoxitin or cefotetan (add oral neomycin + erythromycin for colorectal)

Before and during procedure

Dirtyb (ruptured

viscus)

Cefoxitin or cefotetan ± gentamicin, clindamycin + gentamicin, or another appropriate regimen directed at anaerobes and gram-negative aerobes

Before and for 3–5 days after procedure

Dirtyb (traumatic

wound)

Cefazolin Before and

for 3–5 days after trauma

a

Gentamicin should be added to the amoxicillin regimen for high-risk gastrointestinal and genitourinary procedures; vancomycin should be used in penicillin-allergic patients

b

In these cases, use of antibacterial agents actually constitutes treatment of infection rather than prophylaxis

Vancomycin is recommended only in institutions that have a high incidence of infection with methicillin-resistant staphylococci

The major use of antibacterial prophylaxis is to prevent infections following surgical procedures Antibacterial agents are administered just before the surgical procedure—and, for long operations, during the procedure as well—to ensure high drug concentrations in serum and tissues during surgery The objective

is to eradicate bacteria originating from the air of the operating suite, the skin of the surgical team, or the patient's own flora that may contaminate the wound In all but colorectal surgical procedures, prophylaxis is predominantly directed against staphylococci and cefazolin is the drug most commonly recommended Prophylaxis is intended to prevent wound infection or infection of implanted devices, not all infections that may occur during the postoperative period (e.g., UTIs or pneumonia) Prolonged prophylaxis (beyond 24 h) merely alters the normal flora and favors infections with organisms resistant to the antibacterial agents used A focus on appropriate surgical prophylaxis by the Centers for Medicare and Medicaid Services, coupled with national efforts by surgical societies, appears to be having a favorable impact on the appropriate use of antimicrobial drugs in the surgical setting, although additional improvements are needed