In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa.

Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by Pseudomonas aeruginosa include empirical regimens incorporating two antibiotics from different classes with activity against P. aeruginosa for select at-risk patients to increase the likelihood that the organism will be susceptible to at least one agent. The activity against P. aeruginosa and the rates of cross-resistance of ceftolozane-tazobactam were compared to those of the ß-lactam comparators cefepime, ceftazidime, piperacillin-tazobactam, and meropenem alone and cumulatively with ciprofloxacin or tobramycin. Nonurine P. aeruginosa isolates were collected from adult inpatients at 44 geographically diverse U.S. hospitals. MICs were determined using reference broth microdilution methods. Of the 1,257 isolates collected, 29% were from patients in intensive care units and 39% were from respiratory sites. The overall rate of susceptibility to ceftolozane-tazobactam was high at 97%, whereas it was 72 to 76% for cefepime, ceftazidime, piperacillin-tazobactam, and meropenem. The rate of nonsusceptibility to all four comparator ß-lactams was 11%; of the isolates nonsusceptible to the four comparator ß-lactams, 80% remained susceptible to ceftolozane-tazobactam. Among the isolates nonsusceptible to the tested ß-lactam comparators, less than half were susceptible to ciprofloxacin. By comparison, approximately 80% of the ß-lactam-nonsusceptible isolates were susceptible to tobramycin, for overall cumulative susceptibility rates of 94 to 95%, nearly 10% higher than that of the ciprofloxacin-ß-lactam combinations and approaching that of ceftolozane-tazobactam as a single agent. The rates of susceptibility to ceftolozane-tazobactam were consistently high, with little observable cross-resistance. Ceftolozane-tazobactam monotherapy performed at or above the level of commonly utilized combination therapies on the basis of in vitro susceptibilities. Ceftolozane-tazobactam should be considered for use in patients at high risk for resistant P. aeruginosa infection and as an alternative to empirical combination therapy, especially for patients unable to tolerate aminoglycosides.

Tinidazole for bacterial vaginosis.

Tinidazole has been used for bacterial vaginosis (BV) outside the USA for almost four decades. Tinidazole has recently been resurrected and FDA approved for trichomoniasis and BV in the USA and is being restudied as an alternative to metronidazole for BV. In vitro antimicrobial activity and pharmacokinetics studies indicate that when compared directly with metronidazole, tinidazole has minor but possibly relevant antimicrobial as well as pharmacokinetic advantages. Clinical comparisons have been infrequent, although the limited head-to-head studies indicate minimal therapeutic advantage with tinidazole. Perhaps the more relevant differences relate to the enhanced tolerance and reduced toxicity of tinidazole. Currently, studies are still ongoing directly comparing the clinical efficacy of metronidazole and tinidazole. These studies should establish the role of tinidazole in the treatment of BV; however, cure rates are unlikely to be significantly different.

Tinidazole for the treatment of vaginal infections.

Tinidazole has been used for vaginal infection worldwide but not in the US for > 40 years. Recently, tinidazole has been re-introduced and approved by the FDA for trichomoniasis and restudied as an alternative to metronidazole for bacterial vaginosis. In vitro antimicrobial activity and pharmacokinetics studies indicate that tinidazole has minor but possibly relevant antimicrobial as well as pharmacokinetic advantages when compared directly with metronidazole. Clinical comparison has been infrequent although the limited head-to-head studies indicate minimal therapeutic advantage with tinidazole. Perhaps the more relevant differences relate to the enhanced tolerance and reduced toxicity of tinidazole. Ongoing, as yet incomplete, studies directly comparing the clinical efficacy of metronidazole and tinidazole for bacterial vaginosis should clarify the status of tinidazole; however, cure rates are unlikely to be significantly different. Although uncommon, high-level trichomonal metronidazole resistance can be reliably cured by using tinidazole, which is an invaluable advantage.