Sofia Maraki

Aerosolized plus Intravenous Colistin versus Intravenous Colistin Alone for the Treatment of Ventilator-Associated Pneumonia: A Matched Case-Control Study

OBJECTIVES The incidence of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) organisms is increasing. Intravenous (IV) colistin or aerosolized (AS) plus IV colistin have been recently used to treat these life-threatening infections. The purpose of this study was to compare the efficacy and safety of AS plus IV colistin versus IV colistin alone for patients with MDR VAP due to gram-negative bacteria. METHODS A retrospective matched case-control study was performed at the Intensive Care Unit of the University Hospital of Heraklion, Greece, from January 2005 through December 2008. Forty-three patients with VAP due gram-negative MDR pathogens received AS plus IV colistin and were matched on the basis of age and Acute Physiology and Chronic Health Evaluation II score with 43 control patients who had received IV colistin alone. RESULTS Demographic characteristics, clinical status, and gram-negative isolated pathogens were similar between the 2 treatment groups. Acinetobacter baumannii (66 cases [77%]) was the most common pathogen, followed by Klebsiella pneumoniae (12 cases [14%]) and Pseudomonas aeruginosa (8 cases [9.3%]). No colistin-resistant strains were isolated from patients in either group. No significant differences between the 2 groups were observed regarding eradication of pathogens (P = .679), clinical cure (P = .10), and mortality (P = .289). Eight patients (19%) in each treatment group developed reversible renal dysfunction. No AS colistin-related adverse events were recorded. CONCLUSIONS Addition of AS colistin to IV colistin did not provide additional therapeutic benefit to patients with MDR VAP due to gram-negative bacteria.

Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans.

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.

Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to fosfomycin.

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 beta-lactamase-producing and 24 metallo-beta-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.

Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates

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.

Prospective study of the impact of broad-spectrum antibiotics on the yeast flora of the human gut

The effects of four antibiotics on the yeast flora of the human gut were evaluated. Forty adult cancer patients who received therapy with amoxicillin-clavulanate, ciprofloxacin, sulfamethoxazole-trimethoprim or ampicillin were studied prospectively. Quantitative stool cultures for yeasts were performed immediately before, at the end of and one week after the end of the antibiotic treatment. Amoxicillin-clavulanate caused a higher and more persistent increase in gastrointestinal colonization by yeasts compared to ciprofloxacin, sulfamethoxazole-trimethoprim or ampicillin. The present results are similar to those obtained in a mouse model of gastrointestinal colonization byCandida albicans when the same antibiotics were used.

Susceptibility of Urinary Tract Bacteria to Fosfomycin

ABSTRACT 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.

Stenotrophomonas maltophilia infections in a general hospital: patient characteristics, antimicrobial susceptibility, and treatment outcome.

Introduction Stenotrophomonas maltophilia is acquiring increasing importance as a nosocomial pathogen. Methods We 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. Results Sixty-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.

A 7-year survey of dermatophytoses in Crete, Greece

Dermatophytoses are of worldwide distribution. Epidemiological studies concerning dermatophyte infections have been performed in many countries and differences in the incidence and the aetiological agents have been reported in different geographical locations. This study was undertaken to investigate the prevailing species of dermatophytes in the island of Crete, Greece, and their pattern of infection during a 7‐year period (1997–2003). A total of 5544 samples obtained from 3751 patients with clinically suspected dermatomycoses were examined mycologically in the laboratory of Clinical Microbiology at the University Hospital of Crete, Greece. Skin, hair and nail specimens were subjected to direct microscopy and culture. Dermatophytes were isolated from 520 patients (13.9%). Trichophyton rubrum was the most frequently isolated dermatophyte accounting for 48% of the infections, followed by Microsporum canis (17.9%), Trichophyton mentagrophytes var. interdigitale (14.2%) and Epidermophyton floccosum (6%). Tinea unguium, tinea pedis, tinea corporis, tinea capitis, tinea cruris, tinea manuum and tinea facei were the clinical types of dermatophytoses in decreasing order of frequency. Trichophyton rubrum is the predominant dermatophyte in our area. As the epidemiology of dermatophytoses is changing over time it is important to review periodically the incidence of dermatophytes and their distribution.

Dermatophytoses in Crete, Greece, between 1992 and 1996

Pathological specimens from 1361 patients with clinical manifestations of dermatophytosis from the island of Crete, Greece, were examined for dermatophytes during a 5‐year period (1992‐96). Dermatophytes of the genus Trichophyton, Microsporum and Epidermophyton were isolated from 327 (24%) of the patients. Trichophyton rubrum was the most frequently isolated dermatophyte accounting for 44.4% of the strains, followed by M. canis (25%), T. mentagrophytes var. interdigitale (14.4%) and E. floccosum (7.6%). Less frequent isolates included T. mentagrophytes (3.4%), T. violaceum (3.1%), T. verrucosum (1.8%) and M. gypseum (0.3%). An analysis of the distribution and frequency of the dermatophytes according to the cutaneous area affected and the sex of the patients is also reported.

Use of the GenoType Mycobacterium CM and AS Assays To Analyze 76 Nontuberculous Mycobacterial Isolates from Greece

ABSTRACT Seventy-six nontuberculous mycobacterial isolates obtained from patients living in Greece were analyzed with the GenoType Mycobacterium CM (for common mycobacteria) and AS (for additional species) assays. GenoType correctly identified all but one of the mycobacterial species. For this species, additional probes should be designed and added to the strip.