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Background: We determined the antimicrobial resistance of and changes over time in Pseudomonas aeruginosa isolates from hospitalized patients over the period of 2010-2013, in relation to the patient setting and clinical specimen origin, in a tertiary Greek hospital., Methods: All P. aeruginosa isolates collected from patients with nosocomial infections were processed and cultured according to routine methods. The Vitek 2 automated system was used for antimicrobial susceptibility testing against 9 antimicrobials., Results: Overall, 2,252 P. aeruginosa isolates were tested, and 1,124 (49.91%) were found to be fully susceptible. Among 1,128 resistant isolates, 638 (56.56%) were resistant to ≥3 classes of antipseudomonal antibiotics. Intensive care unit isolates were significantly more resistant than surgical and medical ward isolates, while blood and urine isolates demonstrated the highest resistance rates. Resistance was highest in 2012 and lowest in 2013., Conclusion: Continuous surveillance of antimicrobial resistance is extremely important for controlling P. aeruginosa infections in the hospital setting., (© 2015 S. Karger AG, Basel.)

The reevaluation of "forgotten" antibiotics can identify new therapeutic options against extensively drug-resistant Gram-negative pathogens. We sought to investigate isepamicin in this regard. We retrospectively evaluated the antimicrobial susceptibility to isepamicin of Enterobacteriaceae sp. isolates from unique patients, collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, from 2004 to 2009. Susceptibility testing was done with the automated Vitek 2 system. The breakpoints for susceptibility to isepamicin, tigecycline, and other antibiotics were those proposed by the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM), the FDA, and the CLSI, respectively. A total of 6,296 isolates were studied, including primarily 3,401 (54.0%) Escherichia coli, 1,040 (16.5%) Klebsiella pneumoniae, 590 (9.4%) Proteus mirabilis, and 460 (7.3%) Enterobacter sp. isolates. Excluding the species with intrinsic resistance to each antibiotic, antimicrobial susceptibility was highest for colistin (5,275/5,441 isolates [96.9%]) and isepamicin (6,103/6,296 [96.9%]), followed by meropenem (5,890/6,296 [93.6%]), imipenem (5,874/6,296 [93.3%]), and amikacin (5,492/6,296 [87.2%]). The antimicrobial susceptibility of the 1,040 K. pneumoniae isolates was highest for isepamicin (95.3%), followed by colistin (89.3%) and meropenem (63.0%). Regarding resistant K. pneumoniae isolates, susceptibility to isepamicin was observed for 91.1% of the 392, 87.7% of the 375, and 85.6% of the 111 isolates that were nonsusceptible to the carbapenems, all other aminoglycosides, and colistin, respectively. Isepamicin exhibited high in vitro activity against almost all of the Enterobacteriaceae species. It could particularly serve as a last-resort therapeutic option for carbapenem-resistant K. pneumoniae in our region, where it is endemic, as it does not show considerable cross-resistance with other aminoglycosides.

The past few decades have seen alarming rates of antimicrobial drug resistance. This trend paralleled a lack of conventional methods of discovery of antibiotics with novel mechanisms of action. Although use of mammalian models remains indispensable for preclinical testing of new antimicrobial compounds, combating emerging multidrug-resistant microbial pathogens may require the use of robust, high-throughput experimental systems that can accelerate drug development. The recent discovery of striking similarities in innate immune signaling pathways between Drosophila melanogaster and mammals has led to a surge in the use of this minihost as an alternative model in studying a variety of infectious diseases. Several genetic screens for microbial pathogenicity in Drosophila identified virulence traits shown to be important for infection in mammals that may serve as targets for future drug development. In addition, conventional antimicrobial agents retain full activity in D. melanogaster infection models, which may pave the way for use of this minihost for high-throughput antimicrobial drug screening. Finally, the availability of genetic tools that allow for conditional inactivation of almost every gene in D. melanogaster is anticipated to result in the discovery of novel immunomodulatory mechanisms of action of newly identified antimicrobial compounds. Overall, the powerful genetics of and capacity for large-scale screening in D. melanogaster make this minihost a promising complementary model that may result in a new paradigm in antimicrobial drug discovery. However, antimicrobial drug discovery in such heterologous, phylogenetically disparate minihosts as the fruit flies, would still require further validation in mammalian models.

Background: Acinetobacter baumannii has emerged as a major cause of nosocomial outbreaks. It is particularly associated with nosocomial pneumonia and bloodstream infections in immunocompromised and debilitated patients with serious underlying pathologies. Over the last two decades, a remarkable rise in the rates of multidrug resistance to most antimicrobial agents that are active against A. baumannii has been noted worldwide. We evaluated the rates of antimicrobial resistance and changes in resistance over a 5-year period (2010-2014) in A. baumannii strains isolated from hospitalized patients in a tertiary Greek hospital. Materials and Methods: Identification of A. baumannii was performed by standard biochemical methods and the Vitek 2 automated system, which was also used for susceptibility testing against 18 antibiotics: ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, ciprofloxacin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute criteria, except for tigecycline, for which the Food and Drug Administration breakpoints were applied. Multidrug resistance was defined as resistance to ≥3 classes of antimicrobial agents. Results: Overall 914 clinical isolates of A. baumannii were recovered from the intensive care unit (ICU) (n = 493), and medical (n = 252) and surgical (n = 169) wards. Only 4.9% of these isolates were fully susceptible to the antimicrobials tested, while 92.89% of them were multidrug resistant (MDR), i.e., resistant to ≥3 classes of antibiotics. ICU isolates were the most resistant followed by isolates from surgical and medical wards. The most effective antimicrobial agents were, in descending order: colistin, amikacin, trimethoprim/sulfamethoxazole, tigecycline, and tobramycin. Nevertheless, with the exception of colistin, no antibiotic was associated with a susceptibility rate >40% for the entire study period. The most common phenotype showed resistance against ampicillin/sulbactam, cephalosporins, carbapenems, aminoglycosides, ciprofloxacin, and tigecycline. An extremely concerning increase in colistin-resistant isolates (7.9%) was noted in 2014, the most recent study year. Conclusion: The vast majority of A. baumannii clinical isolates in our hospital are MDR. The remaining therapeutic options for critically ill patients who suffer from MDR A. baumannii infections are severely limited, with A. baumannii beginning to develop resistance even against colistin. Scrupulous application of infection control practices should be implemented in every hospital unit. Lastly, given the lack of available therapeutic options for MDR A. baumannii infections, well-controlled clinical trials of combinations of existing antibiotics are clearly needed. [ABSTRACT FROM AUTHOR]

Background: We determined the antimicrobial resistance of and changes over time in Pseudomonas aeruginosa isolates from hospitalized patients over the period of 2010-2013, in relation to the patient setting and clinical specimen origin, in a tertiary Greek hospital. Methods: All P. aeruginosa isolates collected from patients with nosocomial infections were processed and cultured according to routine methods. The Vitek 2 automated system was used for antimicrobial susceptibility testing against 9 antimicrobials. Results: Overall, 2,252 P. aeruginosa isolates were tested, and 1,124 (49.91%) were found to be fully susceptible. Among 1,128 resistant isolates, 638 (56.56%) were resistant to ≥3 classes of antipseudomonal antibiotics. Intensive care unit isolates were significantly more resistant than surgical and medical ward isolates, while blood and urine isolates demonstrated the highest resistance rates. Resistance was highest in 2012 and lowest in 2013. Conclusion: Continuous surveillance of antimicrobial resistance is extremely important for controlling P. aeruginosa infections in the hospital setting. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Considerable changes in the relative frequency of systemic infections due to various Candida species as well as their in vitro susceptibility patterns have been noted in several parts of the world. We performed an analysis of microbiological data of patients with candidaemia at the University general (tertiary) hospital of Heraklion, Greece. During the study period (March 2001 to July 2006) 140 patients had candidaemia. Among them, 64/140 (46%) had candidaemia due to C. albicans and 76/140 (54%) due to non-albicans species (19/76, 25%, C. glabrata; 30/76, 40%, C. tropicalis; 20/76, 26%, C. parapsilosis; 2/76, 3%, C. lusitaniae; 3/76, 4%, C. krusei; and 2/76, 3%, C. guilliermondii). 75 isolates were tested for in vitro susceptibility to antifungal agents with E-test. No isolate was found to be resistant to amphotericin. From 34 C. albicans isolates, 5 (15%) were not susceptible to itraconazole, and 1 (3%) to fluconazole. The C. guilliermondii and the C. lusitaniae isolates were not susceptible to itraconazole. All 11 C. glabrata isolates were not susceptible to ketoconazole and itraconazole, with only 5 (45%) to fluconazole. In line with results of other relevant studies, we documented that a considerable proportion of Candida bloodstream infections were due to non-albicans Candida species. [ABSTRACT FROM AUTHOR]

Background: Erysipelas is a bacterial infection of the dermis and hypodermis, mostly of streptococcal origin. Bullous erysipelas represents a severe form of the disease. Objective: To evaluate the clinical and microbiological characteristics and treatment of bullous erysipelas. Methods: Patients with a diagnosis of bullous erysipelas who were treated at the Department of Dermatology, University Hospital of Heraklion, Crete, Greece, between the years 1996 and 2001 were retrospectively studied. Results: Fourteen patients (11 women, 3 men) with bullous erysipelas were evaluated. The lesions were located on the legs and face in 9 and 4 patients, respectively. The median duration of disease before hospital admission was 4 days. Eight patients had fever at presentation. Local trauma and various lesions were common causes for pathogen entry. The initial empirical antibiotic treatment included intravenous β-lactams and was modified according to the sensitivities of the isolated strains. Staphylococcus aureus was isolated from 7 (50%), while S. warneri, Streptococcus pyogenes and Escherichia coli grew from the lesions of 3 other patients. Six out of 7 S. aureus strains were methicillin resistant (MRSA) but susceptible to several other non-β-lactam antibiotics such as quinolones, vancomycin, rifampicin and trimethoprim/sulfamethoxazole. Conclusion: Our findings suggest that S. aureus is frequently involved in and probably contributes in synergy with β-hemolytic streptococci to the complicated course of bullous erysipelas. The frequency of MRSA isolation suggests that β-lactam antibiotics may not be sufficient for the treatment of bullous erysipelas anymore, at least in areas with a high incidence of MRSA strains. The role of other classes of antibiotics providing adequate coverage for MRSA has to be evaluated in prospective clinical trials. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a study which examines colistin-resistant gram-negative bacterial isolates among hospital patients in Crete, Greece. The study assessed the drug resistance in patients caused by colistin-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii from urine specimens and bronchial secretions. Results of the study show high susceptibility of colistin from patients to several antimicrobial agents. It suggests that the antimicrobial susceptibility of these colistins is induced by gene suppression from other types of antibiotic types, as a result of antibiotic resistance of biological cost to colistin.

A letter to the editor is presented in response to the article on "A Closer Look on Aerosolized Colistin," by D.H.J. van Leeuwen in the previous issue.

The case of a mentally ill man inadvertently treated with trimethoprim-sulfamethoxazole (TMP-SMX) for 2 y is presented. Quantitative stool cultures revealed a substantially suppressed Gram-negative aerobic flora, while Enterococcus spp. and anaerobes were not affected. Yeasts were moderately increased. TMP-SMX represents an attractive antimicrobial for immunocompromized patients who need the integrity of their intestinal anaerobic flora for colonization resistance. [ABSTRACT FROM AUTHOR]

Carbapenems are broad-spectrum antibiotics increasingly used for the treatment of severe infections. We evaluated the effects of four carbapenems given as monotherapies or in combination with amikacin on the level of gastrointestinal colonisation by Candida albicans in a previously established mouse model. Adult male Crl : CD1 (ICR) BR mice were fed chow containing C. albicans or regular chow. The mice fed with Candida chow had their gut colonised by the yeast. Both groups were subsequently given imipenem, meropenem, ertapenem, doripenem or their combination with amikacin or normal saline subcutaneously for 10 days. Stool cultures were performed immediately before, at the end and 1 week after discontinuation of treatment. Candida-colonised mice treated with the antibiotics had higher counts of the yeast in their stools than control C. albicans-colonised animals treated with saline. All four carbapenems and their combination with amikacin caused a significant increase in C. albicans concentration. Mice fed regular chow and treated with the study antibiotics or saline did not have any Candida in their stools. Dissemination of Candida was not detected in any animal. These data suggest that carbapenems and carbapenem plus amikacin induce substantial increases in the murine intestinal concentration of C. albicans. [ABSTRACT FROM AUTHOR]

Abstract: 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 β-lactamase-producing and 24 metallo-β-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. [Copyright &y& Elsevier]

Abstract: During the last decade, owing to the low effectiveness and high toxicity of older antifungals, new antifungal agents have been released to the market for the treatment of patients with fungal infections. Several randomized controlled trials (RCTs) have been designed to evaluate the effectiveness of caspofungin in comparison with other antifungal agents. This review was conducted to examine further the role of caspofungin in the treatment of patients with fungal, mainly Candida, infections. Two reviewers independently performed the literature search, study selection and data extraction from relevant RCTs. A total of six RCTs comparing caspofungin with amphotericin B (deoxycholate in four and liposomal in one RCT) or fluconazole (in one RCT), which studied a total of 1974 patients, were included in our review. Success of the applied treatment in the clinically evaluable patients was achieved in 496/943 (52.6%) of the caspofungin-treated patients and in 381/852 (44.7%) of the amphotericin B- and lipid amphotericin B-treated patients. Discontinuation due to drug toxicity was significantly less common in patients receiving caspofungin than amphotericin B (odds ratio (OR) 0.25, 95% confidence interval (CI) 0.07–0.85, random effects model). Development of nephrotoxicity, hypokalaemia and fever also occurred significantly less often with caspofungin than amphotericin B (OR 0.23, 95% CI 0.14–0.36, fixed effects model; OR 0.3, 95% CI 0.12–0.76, random effects model; and OR 0.26, 95% CI 0.08–0.79, random effects model, respectively). No difference in mortality was noted. Caspofungin was associated with better clinical outcomes (higher cure and fewer adverse effects) than amphotericin B in the treatment of patients with fungal infections. [Copyright &y& Elsevier]

Abstract: We aimed to evaluate the antimicrobial activity of fosfomycin against Gram-positive non-urinary isolates collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, in 2008. Susceptibility testing was performed by the disk diffusion method for a total of 1846 isolates; 1275 isolates (69.1%) were susceptible to fosfomycin. Specifically, 416/419 Staphylococcus aureus (99.3%) [including 129/130 meticillin-resistant S. aureus (MRSA) isolates] and 745/961 coagulase-negative staphylococci (77.5%) were susceptible to fosfomycin. Among 42 Streptococcus pneumoniae, 64 Streptococcus pyogenes and 93 other streptococcal isolates, 61.9%, 40.6% and 48.4%, respectively, were susceptible to fosfomycin. Fosfomycin was inactive against the 166 enterococcal isolates tested. This old antibiotic may deserve consideration for further studies and use in clinical practice, especially for S. aureus (including MRSA) infections. [Copyright &y& Elsevier]

Abstract: Objectives: The objective of this study was to identify the epidemiological, clinical, and microbiological factors affecting the outcome of peritoneal dialysis (PD)-associated peritonitis. Methods: All patients with PD-associated peritonitis, cared for at the University Hospital of Heraklion from 1990 to 2007, were retrospectively studied. Results: A total of 247 episodes of PD-associated peritonitis occurring in 82 patients were evaluated. The median age of patients was 68 years (range 10–92 years); 51 (62%) were males. There were 104 episodes (42%) of Gram-positive peritonitis, 46 (19%) of Gram-negative peritonitis, 13 (5%) of polymicrobial peritonitis, and 11 (4%) of fungal peritonitis. There were 64 (26%) complicated episodes. The latter included 22 (8.9%) relapses, 13 (5.3%) repeated episodes, 18 (7.3%) catheter removals, and 11 (4.5%) deaths. In multivariate analysis, the presence of a purulent exit-site infection (p <0.001), peritoneal dialysis effluent cell count >100×106/l for more than 5 days (p <0.001), use of antimicrobials during the preceding 3 months (p <0.05), and low serum total protein level on admission (p <0.05) were independent predictors of a complicated course. Conclusions: Exit-site infection, more than 5 days with a peritoneal dialysis effluent cell count >100×106/l, prior use of antimicrobials, and low serum total protein level are potential predictors of complicated PD-associated peritonitis and may distinguish high-risk cases. [Copyright &y& Elsevier]