Athanasia Christidou

Antibiotic use and the risk of carbapenem-resistant extended-spectrum-β-lactamase-producing Klebsiella pneumoniae infection in hospitalized patients: results of a double case–control study

OBJECTIVES To identify the roles of various antibiotics as risk factors for carbapenem-resistant extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) infection (ESBL-KP infection). METHODS Data were collected over 26 months in a tertiary care university hospital with established endemicity of carbapenem-resistant ESBL-KP (ESBL-CRKP). Using a case-case-control design, patients who presented an infection caused by carbapenem-susceptible ESBL-KP (ESBL-CSKP) and patients with ESBL-CRKP infection were compared with a common control group of hospitalized patients. Effects of treatment and duration of treatment with antibiotics were examined, adjusting for major non-antibiotic risk factors and controlling for confounding effects among the antibiotics via logistic regression models. RESULTS Ninety-six ESBL-CRKP cases, 55 ESBL-CSKP cases and 151 controls were analysed. Multivariate analysis, adjusting for major non-antibiotic risk factors, showed that the risk of ESBL-CRKP infection rose with increasing duration of prior treatment with β-lactam/β-lactamase inhibitor combinations [odds ratio (OR) 1.15 per day increase; P = 0.001] and revealed that increased duration of treatment with fluoroquinolones amplified the impact of exposure to carbapenems (and vice versa) on ESBL-CRKP infection risk (OR 1.02 for interaction term; P = 0.009). Duration of prior treatment with fluoroquinolones was also associated with increased risk of ESBL-CSKP infection (OR 1.07 per day increase; P = 0.028), while prior receipt of carbapenems presented a protective effect against ESBL-CSKP infection (OR 0.21; P = 0.003). CONCLUSIONS This study highlights the major role of treatment and duration of treatment with β-lactam/β-lactamase inhibitor combinations and combinations of carbapenems with fluoroquinolones. Clinicians should counterweight the potential benefits of administering these antibiotics against the increased risk of ESBL-CRKP infection.

In vitro susceptibilities of Brucella melitensis isolates to eleven antibiotics

BackgroundBrucellosis is an endemic disease present in many countries worldwide, but it is rare in Europe and North America. Nevertheless brucella is included in the bacteria potentially used for bioterrorism. The aim of this study was the investigation of the antibiotic susceptibility profile of brucella isolates from areas of the eastern Mediterranean where it has been endemic.MethodsThe susceptibilities of 74 Brucella melitensis isolates derived from clinical samples (57) and animal products (17) were tested in vitro. The strains originate from Crete (59), Cyprus (10), and Syria (5). MICs of tetracycline, rifampicin, streptomycin, gentamicin, norfloxacin, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, ampicillin, amoxicillin/clavulanic acid, and erythromycin were detected by E-test method. The NCCLS criteria for slow growing bacteria were considered to interpret the results.ResultsAll the isolates were susceptible to tetracycline, streptomycin, gentamicin, ciprofloxacin, norfloxacin, and levofloxacin. Two isolates presented reduced susceptibility to rifampicin (MIC value: 1.5 mg/l) and eight to SXT (MIC values: 0.75–1.5 mg/l). Erythromycin had the highest (4 mg/l) MIC90value and both norfloxacin and erythromycin the highest (1.5 mg/l) MIC50 value.ConclusionBrucella isolates remain susceptible in vitro to most antibiotics used for treatment of brucellosis. The establishment of a standardized antibiotic susceptibility method for Brucella spp would be useful for resistance determination in these bacteria and possible evaluation of bioterorism risks.

Prophylaxis with urokinase in pediatric oncology patients with central venous catheters.

This study evaluated the effects of urokinase in the prevention of central venous catheter (CVC)-related complications in children with malignancy. Fifteen patients with 16 CVCs (study group A) received an intraluminal application of urokinase (10,000 IU in each catheter lumen for 4 h) once a week. They were monitored prospectively with quantitative blood cultures and ultrasonography (color Doppler ultrasound of the great veins and echocardiography). The rate of complications was compared with that of 15 children with 19 CVCs without thromboprophylaxis, treated the previous year (control group B). The authors found a significantly lower incidence of CVC dysfunction (3/16 versus 13/19), no major thrombosis, fewer CVC-related bacteremias (2/16 versus 8/19), and a higher salvage of CVCs (1/16 versus 5/19 CVC removals due to persistent bacteremia) in the thromboprophylaxis group. Asymptomatic thrombosis rate was also lower (7/16 cases in group A versus 9/11 in group B when sonography was performed). No hemorrhagic complications were noted. Thromboprophylaxis with urokinase seems a safe and effective measure for reducing the rate of CVC-related complications.

Gram-negative bacteremia in non-neutropenic patients: A 3-year review

SummaryThe causative organisms, clinical manifestations, factors influencing prognosis, and other epidemiological characteristics of 81 episodes of bacteremia due to gram-negative organisms, in non-neutropenic patients, were studied retrospectively during a 3-year period (1992–1994) at the Department of Internal Medicine of the University Hospital of Heraklion, Crete, Greece. The gram-negative bacteremia incidence was 2% and the overall mortality 12%. All 81 patients had fever;Escherichia coli was the most frequent organism isolated (from 47 patients −58%) and was associated with shock (9/47), disseminated intravascular coagulation (DIC) (8/47), anuria (5/47), adult respiratory distress syndrome (ARDS) (3/47), and pneumonia (1/47). Other less frequent gram-negative microorganisms wereKlebsiella spp. (ten patients; 12%),Pseudomonas spp. (7; 7%),Salmonella spp. (5; 6%),Enterobacter spp. (5; 6%),Proteus spp. (3; 3.4%),Stenotrophomonas spp. (3; 3.4%), andAcinetobacter spp. (1; 1.2%). ARDS, shock, DIC, anuria, presence of central venous catheter, urinary catheter, unknown origin of infection and inappropriate treatment were significantly associated with a higher death rate. Early initiation of appropriate therapy was the most important intervention that favorably affected the outcome of gram-negative bacteremias in this patient population.

Ochrobactrum anthropi bacteremia in pediatric oncology patients.

Ochrobactrum anthropi is an emerging pathogen in immunocompromised hosts, particularly in patients with indwelling catheters. We report the characteristics of 14 O. anthropi bacteremic episodes in 11 children with Hickman-type central catheters. Children presented with fever and nonspecific clinical manifestations. Bacteremia was successfully treated with antibiotics, but catheter removal was necessary to achieve cure in four cases.

The dynamic relationship between antibiotic use and the incidence of vancomycin-resistant Enterococcus: time-series modelling of 7-year surveillance data in a tertiary-care hospital

The role of antibiotics in the epidemiology of vancomycin-resistant Enterococcus (VRE) has been studied extensively, but controversies remain as to which, and to what extent, antibiotics facilitate the emergence and dissemination of VRE in hospitals. Aggregate data on the use of several antibiotic classes in terms of defined daily doses (DDD) per 100 patient-days (PD), and VRE incidence rates in terms of clinical isolates per 1000 PD, were evaluated during a 7-year period at a tertiary-care hospital. Time-series analysis (autoregressive integrated moving average (ARIMA) and transfer function models) was used to quantify the temporal effect of antibiotic use on VRE incidence and estimate effect-delays. The incidence rate of VRE observed in a specific bimester was found to be a function of its value during the preceding bimester and of prior changes in the volume of use of four antibiotic classes. In particular, an increase of one DDD/100 PD in the use of glycopeptides, fluoroquinolones, extended-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations resulted, independently, in average changes of +0.024, +0.015, + 0.020 and -0.010 isolates per 1000 PD in the incidence of VRE, with average delays of 2, 4, 2 and 6 months, respectively, which explained 56% of the observed variation in VRE rates over time. Efforts to reduce VRE cross-transmission should be supplemented by targeted antibiotic control policies. The use of glycopeptides, broad-spectrum cephalosporins and fluoroquinolones in high amounts should be the targets of such policies. Penicillin-beta-lactamase inhibitor combinations might be suitable substitutes for extended-spectrum cephalosporins.

Risk factors for carbapenem-resistant Klebsiella pneumoniae infection/colonization: A case–case-control study

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly reported worldwide. The aim of the present study was to identify risk factors associated with the development of CRKP infections. A retrospective, case-case-control study was performed at the University Hospital of Heraklion, Greece. The study population included 83 patients from whom CRKP was isolated, 79 from whom carbapenem-sensitive K. pneumoniae (CSKP) was isolated and 161 (control group) from whom K. pneumoniae was not isolated. The median age of CRKP and CSKP patients was 79 (28-101) and 80 (39-97) years, respectively, while that of the controls was 75 (18-100) years. K. pneumoniae was isolated predominantly from urine in both case groups, followed by blood. Independent risk factors for CRKP infection/colonization were admission to ICU (p = 0.004), prior surgical procedure (p = 0.036) and presence of renal disease (p = 0.037), while for CSKP were neurological disease (p = 0.007), and older age (p = 0.011). No association between CRKP and prior antimicrobial exposure was found. Of the entire cohort 40 patients (12%) died; 22 (27%) in the CRKP, 12 (15%) in the CSKP and 6 (4%) in the control group. Isolation of any K. pneumoniae strain was associated with higher mortality compared to the control group (21% vs. 4%; p < 0.005). Mortality was not statistically different between those infected/colonized/with a CRKP or a CSKP strain (p = 0.084). According to these results prior ICU stay, prior surgical procedure and renal disease were independent risk factors for the development of a CRKP infection/colonization.

Candida albicans versus non-albicans bloodstream infection in patients in a tertiary hospital: an analysis of microbiological data.

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.

Investigation of rifampicin resistance mechanisms in Brucella abortus using MS-driven comparative proteomics.

Mutations in the rpoB gene have already been shown to contribute to rifampicin resistance in many bacterial strains including Brucella species. Resistance against this antibiotic easily occurs and resistant strains have already been detected in human samples. We here present the first research project that combines proteomic, genomic, and microbiological analysis to investigate rifampicin resistance in an in vitro developed rifampicin resistant strain of Brucella abortus 2308. In silico analysis of the rpoB gene was performed and several antibiotics used in the therapy of Brucellosis were used for cross resistance testing. The proteomic profiles were examined and compared using MS-driven comparative proteomics. The resistant strain contained an already described mutation in the rpoB gene, V154F. A correlation between rifampicin resistance and reduced susceptibility on trimethoprim/sulfamethoxazole was detected by E-test and supported by the proteomics results. Using 12 836 MS/MS spectra we identified 6753 peptides corresponding to 456 proteins. The resistant strain presented 39 differentially regulated proteins most of which are involved in various metabolic pathways. Results from our research suggest that rifampicin resistance in Brucella mostly involves mutations in the rpoB gene, excitation of several metabolic processes, and perhaps the use of the already existing secretion mechanisms at a more efficient level.

Ochrobactrum anthropi bacteraemia in immunocompetent children.

Ochrobactrum anthropi is an emerging pathogen in immunocompromised patients but infections with the bacterium have very rarely been documented in normal hosts. We report the characteristics of O. anthropi bacteraemia in 11 immunocompetent children, aged 2 months to 7 y, hospitalized in a general hospital during a 5-y period. Children commonly presented with fever, non-specific respiratory or gastrointestinal manifestations, leukocytosis and neutrophilia and had a rapid recovery, even when they did not receive a specific treatment. In 10 cases positive blood cultures were obtained on admission and in all cases subsequent cultures were sterile. In conclusion, O. anthropi may cause bacteraemia in immunocompetent hosts, although further studies are required to clarify whether these isolates represent pseudobacteraemia or whether O. anthropi is a potential pathogen of low virulence.