Our data suggest that prior exposure to fluoroquinolones and antipseudomonal penicillins are independent risk factors for the development of CRKp infections.

Addition of AS colistin to IV colistin did not provide additional therapeutic benefit to patients with MDR VAP due to gram-negative bacteria.

In this investigation, we sought to investigate the characteristics of Citrobacter spp. infections. A retrospective cohort study in a 700-bed, tertiary care, university hospital was carried out during the period from June 1994 to January 2006. Seventy-eight patients (70 adults) with Citrobacter spp. isolates were identified. C. freundii was more common (71.8%), followed by C. koseri (23.1%) and C. braakii (3.8%). The most common associated clinical syndromes were urinary tract infections (52.6% of cases, including eight cases of asymptomatic bacteriuria), as well as intra-abdominal (14.1%), surgical site (7.7%), skin and soft tissue (6.4%), and respiratory tract infections (6.4%). In 29.5% of patients, Citrobacter spp. isolates were associated to polymicrobial infections, principally at sites other than the urinary tract. Antibiograms of 38 consecutive Citrobacter spp. isolates (29 C. freundii) were available. Most active agents were colistin (100%), fosfomycin (100%), imipenem (97.4%), gentamicin (89.5%), nitrofurantoin (89.5%), ciprofloxacin (80.6%), and cefepime (73.7%). Most patients (82.1%) had at least one underlying illness. Combination antimicrobial therapy was administered in 28.2% of cases. One patient died during hospitalization. The length of hospital stay was longer in patients with polymicrobial compared to monomicrobial infections (23 versus 13 days, respectively, p = 0.02). The isolation of Citrobacter species, although rather infrequent, was clinically relevant in the great majority of cases. Further attention should be paid to these pathogens.

Fosfomycin represents a potential last-resort treatment option for infections with certain multidrug-resistant (MDR) Gram-negative pathogens. We evaluated double-drug combinations of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline for in vitro synergy against 100 MDR Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates, using the Etest method. Synergy was defined as a fractional inhibitory concentration index ≤ 0.5. The isolates were consecutively collected at a university hospital in Greece from various clinical specimens. Against 50 serine carbapenemase-producing K. pneumoniae isolates, synergy of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline was observed for 74.0%, 70.0%, 74.0%, 36.0%, 42.0%, and 30.0% of the isolates, respectively. Against 14 extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates, synergy of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline was observed for 78.6%, 42.9%, 42.9%, 7.1%, 42.9%, and 21.4%, respectively; for 20 ESBL-producing E. coli isolates, the corresponding values were 55.0%, 25.0%, 30.0%, 15.0%, 25.0%, and 25.0%; and for 15 MDR P. aeruginosa isolates, the corresponding values were 46.7%, 53.3%, 73.3%, 13.3% , 13.3%, and 13.3%. Antagonism was not observed for any of the combinations tested. Further studies are needed in order to confirm the clinical relevance of the above findings.

This study evaluated the effects of broad-spectrum antibiotics on the gastrointestinal (G.I.) yeast flora of humans and correlated the findings with those obtained from a mouse model of G.I. colonization by Candida albicans. We prospectively studied 46 adult cancer patients who received one of five broad-spectrum antibiotics (ceftriaxone, ceftazidime, ticarcillin-clavulanic acid, imipenem-cilastatin, and aztreonam) as therapy for infections. Quantitative examination of yeast colonization of stools was conducted at the baseline, at the end of antibiotic treatment, and 1 week after discontinuation of therapy. Antibiotics with anaerobic activity (ticarcillin-clavulanic acid) or high G.I. concentrations (ceftriaxone) caused a higher and more sustained increase in G.I. colonization by yeasts than did antibiotics with poor anaerobic activity (ceftazidime and aztreonam) or a low G.I. concentration (imipenem-cilastatin). These results were similar to those obtained with a mouse model of G.I. colonization by C. albicans that involved the same antibiotics. Hence, the mouse model may be useful for evaluation of yeast colonization of the human G.I. tract.

The advancing antimicrobial drug resistance among Enterobacteriaceae renders the evaluation of potential novel therapeutic options necessary. We sought to evaluate the in vitro antimicrobial activity of fosfomycin against multidrug-resistant (MDR) Enterobacteriaceae isolates. Antimicrobial susceptibility to fosfomycin and 12 additional antibiotics of MDR Enterobacteriaceae isolates collected between November 2007 and April 2009 at the University Hospital of Heraklion, Crete, Greece, was examined using the Etest method. A total of 152 MDR Enterobacteriaceae isolates were studied, including Klebsiella pneumoniae (76.3%), Escherichia coli (17.1%), Proteus mirabilis (4.6%) and other species (2.0%).Antimicrobial susceptibility rates were highest for fosfomycin (92.8%), tigecycline (92.1%) and colistin (73.0%) followed by imipenem (35.5%), tetracycline (20.4%), gentamicin (19.7%), trimethoprim/sulfamethoxazole (12.5%) and ciprofloxacin (10.5%). Of the 152 isolates, 85 (55.9%) were extensively drug-resistant (XDR), of which 78 (91.8%) remained susceptible to fosfomycin. Susceptibility to fosfomycin of the 79 carbapenemase-producing, 34 extended-spectrum -lactamase-producing and 24 metallo--lactamase-producing isolates was 94.9%, 94.1% and 83.3%, respectively. In conclusion, in this study fosfomycin exhibited good in vitro antimicrobial activity against MDR and XDR Enterobacteriaceae. We suggest further evaluation of the potential clinical utility of fosfomycin against infections caused by these pathogens.

Introduction Stenotrophomonas maltophilia is acquiring increasing importance as a nosocomial pathogen.MethodsWe retrospectively studied the characteristics and outcome of patients with any type of S. maltophilia infection at the University Hospital of Heraklion, Crete, Greece, between 1/2005–12/2010. S. maltophilia antimicrobial susceptibility was tested with the agar dilution method. Prognostic factors for all-cause in-hospital mortality were assessed with multivariate logistic regression.ResultsSixty-eight patients (median age: 70.5 years; 64.7% males) with S. maltophilia infection, not related to cystic fibrosis, were included. The 68 patients were hospitalized in medical (29.4%), surgical (26.5%), hematology/oncology departments (23.5%), or the intensive care units (ICU; 20.6%). The most frequent infection types were respiratory tract (54.4%), bloodstream (16.2%), skin/soft tissue (10.3%), and intra-abdominal (8.8%) infection. The S. maltophilia-associated infection was polymicrobial in 33.8% of the cases. In vitro susceptibility was higher to colistin (91.2%), trimethoprim/sulfamethoxazole and netilmicin (85.3% each), and ciprofloxacin (82.4%). The empirical and the targeted treatment regimens were microbiologically appropriate for 47.3% and 63.6% of the 55 patients with data available, respectively. Most patients received targeted therapy with a combination of agents other than trimethoprim/sulfamethoxazole. The crude mortality and the mortality and the S. maltophilia infection-related mortality were 14.7% and 4.4%, respectively. ICU hospitalization was the only independent prognostic factor for mortality.Conclusion S. maltophilia infection in a general hospital can be associated with a good prognosis, except for the patients hospitalized in the ICU. Combination reigmens with fluoroquinolones, colistin, or tigecycline could be alternative treatment options to trimethoprim/sulfamethoxazole.

We evaluated the in vitro activity of fosfomycin against urinary isolates in a region in Greece that exhibits considerable antimicrobial resistance by evaluating retrospectively relevant susceptibility data retrieved from the microbiological library of the University Hospital of Heraklion, Crete, Greece. We examined 578 urinary isolates. In total, 516 (89.2%) were susceptible to fosfomycin; 415 isolates were gram negative, and 101 isolates were gram positive. Fosfomycin appears to exhibit good levels of in vitro activity against the examined urinary isolates.