Indications for

Table 14.6 summarizes some of the more important reasons for using p-lactam agents. In addition to being the drugs of choice for treatment of a variety of infections caused by specific bacteria, the /3-lactam drugs are the stalwart agents for empirical treatment of febrile neutropenic patients (168). Unfortunately, the choice of empirical therapy today is less straightforward than in the past, and no obviously best regime exists. Important factors influencing the choice of empirical therapy for febrile neutropenia include the type of cancer chemotherapy being used, expected severity and duration of neurotropenia, the presence of an indwelling long-term catheter, previous use of prophylactic antibiotics or gut decontamination, the patients' symptoms, and the bacterial resistance pattern of the hospital.

Although there has been a striking increase in Gram-positive infections, the morbidity and mortality caused by Gram-negative infections (especially Pseudomonas) suggest that empirical therapy continues to cover these organisms. Supportive evidence exists for the empiric use of ^-lactam drugs in combination with an aminoglycoside. Piperacillin, mezlocillin, azlocillin, ticarcillin, and ceftazidine have shown similar efficacy, with response rates of 55-88% (169-177). Also, a convenient regimen of once-daily dosing of ceftriaxone and amikacin proved as effective as multiple daily-dosing regimens (178). Toxicity for aminogly-coside use led to trials with combinations of two j3-lactam agents. Good results were achieved with multiple regimens, including carbenicillin plus cephalotin, cefoperazone plus aztreonam, cefoperazone plus mezlocillin, ceftazidime plus piperacillin, and ceftazidime plus ticarcillin/clavulanate (169-171). However, double j3-lactam therapy remains controversial because of the possibilities of increased selection of resistant organisms, drug antagonism, prolongation of neutropenia, and potentiation of bleeding disorders.

monotherapy has also been investigated. Supportive data exist for the use of ceftazidime and imipenem (170-172,179-183). However, the increase in frequency of resistant Gram-negative infections, and the finding by some workers that ceftazidime treatment is inadequate, suggest cautions in using ceftazidime monotherapy (170-174). Aztreonam in combination with an agent covering Gram-positive organisms (e.g., vancomycin) is of great utility in patients with penicillin allergy (184, 185). p-Lactam antibiotics have played a key role in improving the care of both immunocompromised and nonimmunocompro-patients. These agents are bactericidal, well tolerated, widely distributed throughout the body, and, most important, clinically effective.

Penicillin G

Penicillinase-

resistant penicillins Arninopenicillins

Extended-spectrum

Extended-spectrum

Meropenem

Primary indication

Drug of choice Can be used

Can be used

Recommended Can be used

Primary indication Can be used

Combination drugs Can be used

Timentin (ticarcillin and clavulanic acid)

Unasyn (ampicillin and sulbactam) Zosyn (Piperacillin and Tazobactam) Monobactams Aztreonam Carbapenems Imipenem

Can be used

Can be used

Can be used

Can be used Efcug of choice

Can be used

Streptococcus pyogenes, Streptococcus pneumoniae, and enterococcal infections

Treponemal infection, prevention of rheumatic fever. Puerperal infection: anaerobic streptococci, Streptomyces agalactia^, clostridial infection, and infection attributed to mouth flora: Grampositive cocci, Gram-negative cocci, and Actiomyces Susceptible Staphylococcus aureus infection

Prevention of endocarditis

Infection of respiratory tract in areas with low prevalence of /3-lactamase and Haemophilus influenzae.

Urinary tract infection

Pseudomonas spp.

Infection of urinary tract, respiratory tract, and bone with Gramnegative bacilli and mixed aerobic/anaerobic infections

Mixed bacterial infection: community and hospital acquired pneumonia, especially if aspiration, intra-abdominal and gynecological infections, osteomyelitis, and skin-structure infection

Mixed bacterial infection: intra-abdominal: obstetric, gynecologic, soft-

tissue, bone infection Mixed bacterial infection: lower respiratory tract, intra-abdominal, skin, and soft tissue infection Urinary tract, lower respiratory tract, skin-structure, and intraabdominal infections, patients with penicillin allergy Resistant Gram-negative bacilli infection with ESBL. Nosocomial infection, when multiresistant Gram-negative bacilli or mixed infections are suspected Nosocomial infection when multiresistant Gram-negative bacilli or mixed infections are suspected. Meningitis in pediatric population older than 3 months

Cefepime Skin Reaction

First-generation cephalosporins

Second-generation cefuroxime Cefoxitin

Cefotetan

Third-generation Ceftriaxone

Ceftazidime

Cefoperazone Cefepime

Drug of choice Can be used

Can be used

Drug of choice Recommended Can be used

Drug of choice

Recommended Can be used

Should be used Can be used Drug of choice

Can be used

Can be used

Prophylaxis of surgical procedures

Infection attributed to S. aureus or nonenterococcal streptococci (e.g, skin and soft tissue infections, pharyngitis) Respiratory tract infections: pneumonia epiglottis, complicated sinusitis, soft-tissue infections, bacteremia Pelvic inflammatory disease (+ doxycicline) Prophylaxis of colorectal surgery

Mixed aerobic/anaerobic infections: intra-abdominal infections, skin and soft-tissue infections, including diabetic foot infections and decubitus ulcers

Mixed aerobic/anaerobic infections: intra-abdominalinfections, skin and soft-tissue infections, including diabetic foot infections and decubitus ulcers

Neisseria gonhorroea chancroid, Lyme disease if neurological involvement, carditis, arthritis, or refractory late constitutional symptoms

Meningitis attributed to H. influenzae, Neisseria meningitis, and penicillin-resistant S. pneumoniae Nosocomial infection caused by a sensitive Gram-negative baccilli:

pneumoniae, wound, and complicated urinary tract infections Home treatment of chronic infections

Infections that are likely attributable to Pseudomonas aeruginosa

Empiric treatment of febrile neutropenia Meningitis attributed to P. aeruginosa Empiric treatment of febrile neutropenia

Infections of lower respiratory tract, urinary tract, skin and soft tissue, and in female reproductive tract

Good H influenzae coverage

Slightly less anaerobic coverage but better coverage than cefoxitin Once-daily dosing, good CSF penetration

Moderate antipseudomonal activity

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