Antibiotic/adjuvant combinations (ceftriaxone + sulbactam + adjuvant disodium edetate) as an alternative empiric therapy for the treatment of nosocomial infections: Results of a retrospective study.

OBJECTIVE: Carbapenems are one of the last therapeutic options to treat various bacterial infections including multidrug resistant (MDR) nosocomial infections. However, excessive and inappropriate prescription of this drug has recently led to an epidemic rise in carbapenem resistance. Optimizing antibiotic utilization and exploring alternate options can be a potential way to control carbapenem resistance. The aim of this study was to assess the clinical efficacy of novel antibiotic adjuvant entity (ceftriaxone + sulbactam + ethylenediaminetetraacetic acid [EDTA] [CSE-1034]) in the treatment of various nosocomial infections. METHODS: Older patients suffering from hospital-acquired pneumonia, ventilator-associated pneumonia, and complicated urinary tract infections who received CSE-1034 as empirical therapy were evaluated. CSE-1034 therapy was initiated empirically and continued based on the results of culture sensitivity and clinical outcome. RESULTS: In total, 59 culture-positive patients with mean age of 57 ± 19 years were evaluated in this retrospective study. Escherichia coli was the most predominant pathogen isolated, followed by Acinetobacter baumannii, Klebsiella pneumonia, and Pseudomonas aeruginosa. Microbial sensitivity analysis has shown that isolates from all patients exhibited resistance to multiple classes of antibiotics. Isolated pathogens from 78% were sensitive to meropenem, 86% to CSE-1034, and 100% to colistin except Proteus species. Overall assessment of clinical outcome has shown that 83% cases were cured with CSE-1034 monotherapy, 12% with CSE-1034 and colistin combination therapy, and 5% were cured with alternate meropenem therapy. CONCLUSION: From this study, it can be concluded that ceftriaxone + sulbactam + EDTA alone or in combination with colistin can be an effective empiric treatment of various MDR nosocomial infections and can serve as an effective alternative to carbapenems.

Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections.

Here we review the effectiveness and safety of high-dose tigecycline (200mg daily). A systematic search was performed in PubMed and Scopus databases as well as of abstracts presented at scientific conferences. Eight studies (263 patients; 58% critically ill) were included, comprising one randomised controlled trial (RCT), four non-randomised cohorts and three case reports. Klebsiella pneumoniae was the most commonly isolated pathogen (reported in seven studies). In the RCT, response in the clinically evaluable patients was 85.0% (17/20) in the 100mg every 12h (q12h) group and 69.6% (16/23) in the 75mg q12h group (P=0.4). More episodes of diarrhoea, treatment-related nausea and vomiting developed in the high-dose group (14.3% vs. 2.8%, 8.6% vs. 2.8% and 5.7% vs. 2.8%, respectively; P>0.05 for all comparisons). Three (8.6%) and 7 (19.6%) patients died in the 200mg and 150mg daily dose groups, respectively. The cohort studies enrolled patients with severe infections, including ventilator-associated pneumonia and complicated intra-abdominal infections. Mortality with high-dose tigecycline (100mg q12h) in the cohort studies ranged from 8.3% to 26%; mortality in the low-dose groups (50mg q12h) ranged from 8% to 61% and depended on the severity of the underlying infection. There are limited available data regarding the effectiveness and safety of high-dose tigecycline. Most of the data come from critically ill patients with difficult-to-treat infections. Pharmacokinetic/pharmacodynamic properties of tigecycline suggest that high-dose regimens may be more effective than low-dose regimens. Candidates for administration of high-dose tigecycline should be also defined.