Evangelos I. Kritsotakis

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.

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.

Case-Mix Adjustment Approach to Benchmarking Prevalence Rates of Nosocomial Infection in Hospitals in Cyprus and Greece

OBJECTIVE To examine the effect of heterogeneous case mix for a benchmarking analysis and interhospital comparison of the prevalence rates of nosocomial infection. DESIGN Cross-sectional survey. SETTING Eleven hospitals located in Cyprus and in the region of Crete in Greece. METHODS The survey included all inpatients in the medical, surgical, pediatric, and gynecology-obstetrics wards, as well as those in intensive care units. Centers for Disease Control and Prevention criteria were used to define nosocomial infection. The information collected for all patients included demographic characteristics, primary admission diagnosis, Karnofsky functional status index, Charlson comorbidity index, McCabe-Jackson severity of illness classification, use of antibiotics, and prior exposures to medical and surgical risk factors. Outcome data were also recorded for all patients. Case mix-adjusted rates were calculated by using a multivariate logistic regression model for nosocomial infection risk and an indirect standardization method.Results. The overall prevalence rate of nosocomial infection was 7.0% (95% confidence interval, 5.9%-8.3%) among 1,832 screened patients. Significant variation in nosocomial infection rates was observed across hospitals (range, 2.2%-9.6%). Logistic regression analysis indicated that the mean predicted risk of nosocomial infection across hospitals ranged from 3.7% to 10.3%, suggesting considerable variation in patient risk. Case mix-adjusted rates ranged from 2.6% to 12.4%, and the relative ranking of hospitals was affected by case-mix adjustment in 8 cases (72.8%). Nosocomial infection was significantly and independently associated with mortality (adjusted odds ratio, 3.6 [95% confidence interval, 2.1-6.1]). CONCLUSION The first attempt to rank the risk of nosocomial infection in these regions demonstrated the importance of accounting for heterogeneous case mix before attempting interhospital comparisons.

Device‐Associated Nosocomial Infection Rates in Intensive Care Units in Greece

Site-specific, risk-adjusted incidence rates of intensive care unit (ICU)-acquired infections were obtained through standardized surveillance in 8 ICUs in Greece. High rates were observed for central line-associated bloodstream infection (12.1 infections per 1,000 device-days) and ventilator-associated pneumonia (12.5 infections per 1,000 device-days). Gram-negative microorganisms accounted for 60.4% of the isolates recovered, and Acinetobacter species were predominant. To reduce infection rates in Greek ICUs, comprehensive infection control programs are required.

Murine typhus in central Greece: epidemiological, clinical, laboratory, and therapeutic-response features of 90 cases

OBJECTIVES To document and evaluate the clinico-epidemiological profile of murine typhus during the re-emergence of the disease in a previously endemic focus in central Greece. METHODS This was a 5-year, hospital-based, observational study, in which 90 adult patients with murine typhus were prospectively identified and studied. RESULTS Most cases of the disease occurred in rural (52%) and semi-urban (34%) settings, with a seasonal frequency peak during the late summer. The triad of fever, headache, and rash was present in 64% of the patients within 2 days of hospital admission. Normal white blood cell counts (63%), thrombocytopenia (81%), and a high erythrocyte sedimentation rate (93%) were the main hematological findings upon presentation. Elevated aminotransferases (>84%), hypoalbuminemia (81%), and hyponatremia (36%) were prominent biochemical abnormalities. Pulmonary, neurological, and renal complications were noted in 26% of the patients and subsided after specific treatment. The duration of fever was shorter in patients treated with doxycycline (median 3 days) compared to ofloxacin (p=0.001) or doxycycline plus ofloxacin (p=0.009). CONCLUSIONS Murine typhus has the potential to cause significant morbidity. Awareness of the disease in endemic areas, early recognition of its clinical and laboratory features, and prompt administration of effective treatment are key factors to prevent potentially severe complications.

Surveillance of surgical site infections at a tertiary care hospital in Greece: Incidence, risk factors, microbiology, and impact

BACKGROUND In this first attempt to implement a standardized surveillance system of surgical site infections (SSI) in a Greek hospital, our objective was to identify areas for improvement by comparing main epidemiologic and microbiologic features of SSI with international data. METHODS The National Nosocomial Infections Surveillance (NNIS) system protocols were employed to prospectively collect data for patients in 8 surgical wards who underwent surgery during a 9-month period. SSI rates were benchmarked with international data using standardized infection ratios. Risk factors were evaluated by multivariate logistic regression. RESULTS A total of 129 SSI was identified in 2420 operations (5.3%), of which 47.3% developed after discharge. SSI rates were higher for 2 of 20 operation categories compared with Spanish and Italian data and for 12 of 20 categories compared with NNIS data. Gram-positive microorganisms accounted for 52.1% of SSI isolates, and Enterococci were predominant. Alarming resistance patterns for Enterococcus faecium and Acinetobacter baumannii were recorded. Potentially modifiable risk factors for SSI included multiple procedures, extended duration of operation, and antibiotic prophylaxis. SSI was associated with prolongation of postoperative stay but not with mortality. CONCLUSION Comparisons of surveillance data in our hospital with international benchmarks provided useful information for infection control interventions to reduce the incidence of SSI.

Surveillance of Monthly Antimicrobial Consumption Rates Stratified by Patient-Care Area: A Tool for Triggering and Targeting Antibiotic Policy Changes in the Hospital

Abstract The profile and temporal trends of antimicrobial use were investigated at a university hospital. Aggregate data were analyzed according to the ATC/DDD methodology. During 1998-2002, hospital-wide antimicrobial use increased by 22%, from 86.97 to 106.24 defined daily doses per 100 bed-days [DDD/100BD]. Pooled usage rates in DDD/100BD, overall percentage increases and annual average increase rates were respectively 109.97, 35.6%, 8.1 for Medical wards, 98.21, 48.7%, 9.1 for Intensive Care Units and 74.46, 34.3%, 5.7 for Hemato-oncology wards. Surgical wards had a fairly constant usage rate (98.36). A shift towards the newer broad-spectrum antibiotics, to the detriment of the older penicillins and cephalosporins, was noted in all hospital areas. Surveillance of antimicrobial consumption using the ATC/DDD system provided a clear picture of its profile. Monthly rates over a sufficient surveillance period allowed the assessment of temporal trends. Stratification of rates according to clinical service allowed areas of concern to be specified and targeted antibiotic policy changes to be initiated.

Epidemiology and Molecular Analysis of Intestinal Colonization by Vancomycin-Resistant Enterococci in Greek Hospitals

ABSTRACT From 1,246 specimens collected from 13 Greek hospitals, 266 vancomycin-resistant enterococci strains were isolated from 255 patients (20.5%). The VanA phenotype was present in 82 (30.8%) strains, the VanB phenotype in 17 (6.4%) strains, the VanC1 phenotype in 152 (57.1%) strains, and the VanC2/C3 phenotypes in 15 (5.6%) strains. When only VanA and VanB phenotypes were considered, the overall prevalence was 7.5%. Eighty-six isolates exhibiting the VanA or VanB phenotype were analyzed by pulsed-field gel electrophoresis (PFGE), and 46 PFGE groups were found.

The Associations Between Negative Relating and Aggression in the Dating Relationships of Students From Greece

The study examined the prevalence rates and severity of four aspects of dating aggression (physical assault, injury, sexual coercion, and psychological aggression) and their associations with negative relating tendencies in a convenience sample of 247 university students from Greece. A high proportion of the students were both aggressors and victims of aggression by their partners. Prevalence and chronicity of the majority of the types of aggression were higher for male than for female students. There were few gender differences in the prevalence of being a victim of aggression. Although, as predicted, both aggressors and victims had higher negative relating scores than those who were neither aggressors nor victims, few of the differences were statistically signifi cant. However, injury, sexual coercion, and severe assault were signifi cantly correlated with relating from a position of relative strength (upperness). Being injured was signifi cantly correlated with relating from a position of relative weakness (lowerness).

Prevalence, incidence burden and clinical impact of healthcare-associated infections and antimicrobial resistance: a national prevalent cohort study in acute care hospitals in Greece

Background Assessing the overall burden of healthcare-associated infections (HAIs) is challenging, but imperative in evaluating the cost-effectiveness of infection control programs. This study aimed to estimate the point prevalence and annual incidence of HAIs in Greece and assess the excess length of stay (LOS) and mortality attributable to HAIs, overall and for main infection sites and tracer antimicrobial resistance (AMR) phenotypes and pathogens. Patients and methods This prevalent cohort study used a nationally representative cross-section of 8,247 inpatients in 37 acute care hospitals to record active HAIs of all types at baseline and overall LOS and in-hospital mortality up to 90 days following hospital admission. HAI incidence was estimated using prevalence-to-incidence conversion methods. Excess mortality and LOS were assessed by Cox regression and multistate models correcting for confounding and time-dependent biases. Results HAIs were encountered with daily prevalence of 9.1% (95% confidence interval [CI] 7.8%–10.6%). The estimated annual HAI incidence was 5.2% (95% CI 4.4%–5.3%), corresponding to approximately 121,000 (95% CI 103,500–123,700) affected patients each year in the country. Ninety-day mortality risk was increased by 80% in patients with HAI compared to those without HAI (adjusted hazard ratio 1.8; 95% CI 1.3–2.6). Lower respiratory tract infections, bloodstream infections, and multiple concurrent HAIs doubled the risk of death, whereas surgical site and urinary tract infections were not associated with increased mortality. AMR had significant impact on the daily risk of 90-day mortality, which was increased by 90%–110% in patients infected by carbapenem-resistant gram-negative pathogens. HAIs increased LOS for an average of 4.3 (95% CI 2.4–6.2) additional days. Mean excess LOS exceeded 20 days in infections caused by major carbapenem-resistant gram-negative pathogens. Conclusion HAIs, alongside with increasing AMR, pose significant burden to the hospital system. Burden estimates obtained in this study will be valuable in future evaluations of infection prevention programs.