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Summary Background Israel has been the destination of large numbers of illegal migrants from East African countries in recent years. Despite efforts to detect and treat active tuberculosis (TB) at the border, 75% of all active TB cases diagnosed in our hospital were illegal migrants. In 2012, there was a large-scale TB exposure in our maternity ward, neonatal, and paediatric intensive care units following the admission of an infectious but apparently asymptomatic migrant who was in labour. A hospital-wide screening programme was subsequently implemented to prevent exposure of patients and staff to TB. Aim To report the results of the first year of this intervention in the maternity hospital. Methods All illegal migrants from countries where TB is highly prevalent were screened by chest radiography (CR) upon admission to the maternity hospital. The results were immediately categorized by a radiologist as either ‘suggestive of active pulmonary TB’ or ‘non-suggestive’. Patients with CR suggestive of TB were placed in airborne isolation and underwent further evaluation. Findings Four hundred and thirty-one apparently asymptomatic migrant women underwent CR screening. Most (363, 84%) presented in labour. Eleven women (2.6%) had a CR suggestive of active pulmonary TB which was confirmed in three (0.7% of screened women). No TB cases were missed by the CRs. Neither patients nor hospital staff were exposed to TB. Conclusion Targeted CR screening for TB among high-risk women upon their admission to a maternity hospital had a high yield and was an effective strategy to prevent in-hospital transmission of TB. [ABSTRACT FROM AUTHOR]

BACKGROUND: Over the last decade, extremely-drug-resistant (XDR) strains of Klebsiella pneumoniae have emerged worldwide, mainly as a result of patient-to-patient spread. The predominant clone, sequence type 258 (ST258), is associated with high morbidity and mortality, and is a worldwide threat to public health. It was hypothesized that reduced susceptibility to chlorhexidine, the most widely used hospital disinfectant, may contribute to the endemic nature of this strain. AIM: To characterize and compare the susceptibility of the epidemic K. pneumoniae clone ST258 and non-epidemic K. pneumoniae clones to chlorhexidine. METHODS: The minimum inhibitory concentration (MIC) of chlorhexidine was determined in 126 XDR K. pneumoniae clinical isolates using agar dilution. Expression of three different efflux pumps -cepA, acrA and kdeA - was investigated in the absence and presence of chlorhexidine using quantitative real-time polymerase chain reaction. Heteroresistance to chlorhexidine was identified using population analysis. FINDINGS: The MIC of chlorhexidine was higher for K. pneumoniae ST258 (N = 70) than other K. pneumoniae sequence types (N = 56); 99% of ST258 isolates had MICs >32 [mu]g/mL, compared with 52% of other K. pneumoniae sequence types (P < 0.0001). Reduced susceptibility to chlorhexidine appeared to be independent of the expression of cepA, acrA and kdeA efflux pumps. Chlorhexidine-resistant subpopulations were observed independent of the bacterial sequence type or the MIC. CONCLUSIONS: Reduced susceptibility to chlorhexidine may contribute to the success of XDR K. pneumoniae as a nosocomial pathogen, and may provide a selective advantage to the international epidemic strain K. pneumoniae ST258. The heterogeneous nature of chlorhexidine-resistant subpopulations suggests that this phenomenon might not be rendered genetically. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2010; 16: 102–111 Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries—chiefly Greece and Israel—have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice. [ABSTRACT FROM AUTHOR]

Bacterial infections are becoming more difficult to treat. At the present time c. 70% of nosocomial infections are resistant to at least one antimicrobial drug that previously was effective for the causative pathogen. Pathogens that are notorious for their virulence and ability to develop resistance include Staphylococcus aureus, Enterococcus spp., members of the Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter species. Notable resistance patterns that have emerged include methicillin resistance in S. aureus, which started in the healthcare setting but has now moved into the community. Vancomycin resistance in enterococci is frequently seen, and vancomycin resistance in methicillin-resistant S. aureus is a public health threat. Resistance patterns seen in pseudomonal and Acinetobacter infections are rapidly shifting. The situation has become sufficiently serious for clinical opinion leaders to call upon governments for assistance in addressing the problem. In this worsening environment, in which patients are at progressively greater risk of untreatable infections, clear recommendations for prescribers are urgently needed. Severity of infection and underlying conditions are key issues, as patients with the most serious diseases are those in most urgent need, and improvements in our ability to predict likely infecting pathogens when empirical therapy is necessary are needed. Risk-factors and local resistance patterns must be accounted for, and initial empirical therapy should be adequately broad spectrum and adequately dosed. Agents must be highly active, able to penetrate adequately to the site of infection, safe, and well-tolerated. [ABSTRACT FROM AUTHOR]

Summary: The incidence of multi-drug-resistant Acinetobacter baumannii bloodstream infections (BSIs) increased two- to four-fold in three Israeli hospitals between 1997 and 2002, accounting for 3.5–18% of all hospital-acquired BSIs. This was associated with increasing carbapenem resistance reaching 35–54%, and by a dramatic increase in carbapenem consumption. In-hospital fatality rates ranged between 47% and 58% and were significantly higher than those seen with other nosocomial Gram-negative pathogens. A. baumannii was not restricted to intensive care units, but had spread to all hospital wards. Multi-drug-resistant A. baumannii has the potential to reach endemicity in hospitals and warrants more vigorous and innovative efforts to limit its spread. [Copyright &y& Elsevier]

Summary: We report a nosocomial outbreak of urinary tract infection by extremely drug resistant Pseudomonas aeruginosa, susceptible only to colistin. Infection in three patients followed urodynamic studies. Two of the three patients were children, one of whom also developed urosepsis. The investigation led to detection of contaminated pressure transducers. Genotyping confirmed that patient and transducer isolates were identical. These transducers were not labelled as ‘single use only’ despite the possibility that contaminated urine may reflux and mix with the fluid in the device. The issue of re-usable versus single-use urodynamic devices is discussed. [ABSTRACT FROM AUTHOR]

Antibacterial therapy is one of the most important medical developments of the twentieth century; however, the spread of resistance in healthcare settings and in the community threatens the enormous gains made by the availability of antibiotic therapy. Infections caused by resistant bacteria lead to up to two-fold higher rates of adverse outcomes compared with similar infections caused by susceptible strains. These adverse outcomes may be clinical or economic and reflect primarily the failure or delay of antibiotic treatment. The magnitude of these adverse outcomes will be more pronounced as disease severity, strain virulence, or host vulnerability increases. The negative impacts of antibacterial resistance can be measured at the patient level by increased morbidity and mortality, at the healthcare level by increased resource utilization, higher costs and reduced hospital activity and at the society level by antibiotic treatment guidelines favouring increasingly broad-spectrum empiric therapy. In this review we will discuss the negative impact of antibiotic resistance on patients, the healthcare system and society. [ABSTRACT FROM AUTHOR]

The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death. Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) < 50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis. Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14–1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 hr after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03–1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19–1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen. The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 hr after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival. [ABSTRACT FROM AUTHOR]

The aim of the study was to measure the impact of antibiotic exposure on the acquisition of colonization with extended-spectrum β-lactamase-producing Gram-negative bacteria (ESBL-GNB) accounting for individual- and group-level confounding using machine-learning methods. Patients hospitalized between September 2010 and June 2013 at six medical and six surgical wards in Italy, Serbia and Romania were screened for ESBL-GNB at hospital admission, discharge, antibiotic start, and after 3, 7, 15 and 30 days. Primary outcomes were the incidence rate and predictive factors of new ESBL-GNB colonization. Random forest algorithm was used to rank antibiotics according to the risk of selection of ESBL-GNB colonization in patients not colonized before starting antibiotics. We screened 10 034 patients collecting 28 322 rectal swab samples. New ESBL-GNB colonization incidence with and without antibiotic treatment was 22/1000 and 9/1000 exposure-days, respectively. In the adjusted regression analyses, antibiotic exposure (hazard ratio (HR) 2.38; 95% CI 1.29–4.40), age 60–69 years (HR 1.19; 95% CI 1.05–1.34), and spring season (HR 1.25; 95% CI 1.14–1.38) were independently associated with new colonization. Monotherapy ranked higher als combination therapy in promoting ESBL-GNB colonization. Among monotherapy, cephalosporins ranked first followed by tetracycline (second), macrolide (fourth) and cotrimoxazole (seventh). Overall the ranking of cephalosporins was lower when used in combination. Among combinations not including cephalosporins, quinolones plus carbapenems ranked highest (eighth). Among sequential therapies, quinolones ranked highest (tenth) when prescribed within 30 days of therapy with cephalosporins. Impact of antibiotics on selecting ESBL-GNB at intestinal level varies if used in monotherapy or combination and according to previous antibiotic exposure. These finding should be explored in future clinical trials on antibiotic stewardship interventions. NCT01208519. [ABSTRACT FROM AUTHOR]

Intestinal carriage with extended spectrum β-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35–48 days after randomization (V4). ClinicalTrials.gov NCT02472600. The trial was funded by the European Commission (FP7). Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4–6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT). Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted. [ABSTRACT FROM AUTHOR]

The rise in carbapenem resistance among Gram-negative bacteria has renewed interest in colistin. Recently, the EUCAST-CLSI Polymyxin Breakpoints Working Group declared that broth microdilution (BMD) is the only valid method for colistin susceptibility testing. BMD is not easily incorporated into the routine work of clinical laboratories, and usually this test is incorporated serially, resulting in delayed susceptibility reporting. We tested a strategy of combining VITEK® 2 with a 2 μg/mL colistin agar dilution (VITEK® 2/AD) screening plate to improve performance and time to reporting of colistin susceptibility. Colistin susceptibility for 364 clinical isolates was determined by VITEK® 2/AD and compared with the reference standard BMD according to the ISO 20776-1:2007 and CLSI guidelines. The EUCAST colistin susceptibility breakpoint of ≤2 μg/mL was used. Escherichia coli NCTC 13846 served as quality control strain. Agreement, very major error (VME) and major error rates were determined using ISO 20776-2:2007. The VME rate for VITEK® 2 alone was 30.6% (15/49, 95% CI 18.3–45.4%), and was reduced to 10.2% (5/49, 95% CI 3.4–22.2%) using the VITEK® 2/AD combined testing. The combined testing had categorical agreement with BMD of 97% (354/364, 95% CI 95.0–98.7%), and a major error (ME) rate of 1.6% (5/315, 95% CI 0.5–3.7%). Using the combined testing, even against challenging strains, 349 (95.8%, 95% CI 93.3–97.7%) colistin susceptibility results could be reported, and only 15 isolates required further analysis by BMD. Our method is simple to apply and allows rapid reporting of colistin susceptibility. [ABSTRACT FROM AUTHOR]

Carriers of carbapenem-resistant Klebsiella pneumoniae (CRKP) are increasingly recognised through active surveillance in much of the world. We studied incidence, aetiology and predictors of bloodstream infections (BSI) among such carriers. Via a retrospective cohort study conducted in a tertiary care teaching hospital, we examined occurrence of BSI within 45 days of CRKP carrier detection. Three nested case-control studies were conducted to analyse parameters associated with all-cause (ALL), Gram-negative rod (GNR) and CRKP BSI. Cases and controls were compared with respect to demographics, clinical parameters and recent receipt of antibiotics. A total of 431 patients were identified as CRKP carriers (28% by clinical culture, 72% by rectal surveillance), mean age was 75.2 years. Twenty percent of the patients (n = 85) developed BSI, of them 80% (n = 68) with GNR. Of 83 GNR isolates, 58 (70%) were Enterobacteriaceae, of which 19 were CRKP and 20 were extended-spectrum β-lactamase (ESBL) producers (23% and 24% of total GNR, respectively); 29% of the GNR isolates were nonfermenters (14.5% Pseudomonas aeruginosa, 14.5% Acinetobacter baumannii). Mechanical ventilation predicted ALL BSI (p = 0.04), whereas Clostridium difficile-associated diarrhoea predicted GNR BSI (p = 0.04). Receipt of broad-spectrum antibiotics (piperacillin-tazobactam, amikacin, imipenem) was significantly associated with ALL BSI or GNR BSI. No exposure independently predicted CRKP BSI. We conclude that patients detected as CRKP carriers are at high risk for BSI within 45 days of detection, primarily with multidrug-resistant GNR. Lack of predictive factors differentiating between pathogens and associated high mortality raises once more the dilemma regarding the appropriate empiric therapy for CRKP carriers who develop severe sepsis. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Acinetobacter baumannii ( CRAB) is an increasingly common nosocomial pathogen. We sought to identify clinical and microbiological predictors of 14-day mortality among patients with CRAB bacteraemia. This case-control study included all adult patients in one Israeli hospital with CRAB on blood culture between July 2008 and June 2011. Cases were defined as patients who died within 14 days of bacteraemia onset and controls as patients who survived over 14 days. Sequence-typing of the bla OXA-51-like gene and REP- PCR identified CRAB clone groups. Logistic regression was performed to analyze predictors of 14-day all-cause mortality. To correct for differences in treatment onset, Cox regression was used to examine the effect of receiving an active antibiotic. Eighty-three cases and 89 controls were included. Six major CRAB clone groups were identified, with 14-day mortality ranging from 17 to 66%. Independent predictors of 14-day mortality were severity of illness ( OR = 1.38 for each 1-point increase in Sequential Organ Failure Assessment ( SOFA) score; 95% CI, 1.21, 1.56), independence in activities of daily living ( ADL) on admission ( OR = 3.40; 95% CI, 1.20, 9.67, for fully dependent vs. independent), surgery before bacteraemia ( OR = 0.25; 95% CI, 0.11, 0.59) and clone group ( OR = 7.76; 95% CI, 2.52, 23.85, for the most virulent group vs. the reference group). In the multivariate Cox model using a propensity score to adjust for SOFA, clone, ADL and surgery, active antibiotic treatment was protective ( HR = 0.30; 95% CI, 0.15, 0.60). Differences in virulence between CRAB clones may partly explain heterogeneous results in previous studies of mortality following CRAB infection. [ABSTRACT FROM AUTHOR]

Patients newly admitted to rehabilitation centres are at high risk of colonization with multidrug-resistant bacteria because many of them have experienced prolonged stays in other healthcare settings and have had high exposure to antibiotics. We conducted a prospective study to determine the prevalence of and risk factors for colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae ( ESBL- PE) in this population. Subjects were screened by rectal swab for ESBL- PE within 2 days of admission. Swabs were plated on chromagar ESBL plates and the presence of ESBL was verified by a central laboratory. A multilevel mixed effects model was used to identify risk factors for ESBL- PE colonization. Of 2873 patients screened, 748 (26.0%) were positive for ESBL- PE. The variables identified as independently associated with ESBL- PE colonization were: recent stay in an acute-care hospital for over 2 weeks ( OR = 1.34; 95% CI, 1.12, 1.6), history of colonization with ESBL- PE ( OR = 2.97; 95% CI, 1.99, 4.43), unconsciousness on admission ( OR = 2.59; 95% CI, 1.55, 4.34), surgery or invasive procedure in the past year ( OR = 1.49; 95% CI, 1.2, 1.86) and antibiotic treatment in the past month ( OR = 1.80; 95% CI, 1.45, 2.22). The predictive accuracy of the model was low (area under the ROC curve 0.656). These results indicate that ESBL- PE colonization is common upon admission to rehabilitation centres. Some risk factors for ESBL- PE colonization are similar to those described previously; however, newly identified factors may be specific to rehabilitation populations. The high prevalence and low ability to stratify by risk factors may guide infection control and empirical treatment strategies in rehabilitation settings. [ABSTRACT FROM AUTHOR]

In June 2012, Israeli guidelines for laboratories were published defining the recommended methods for diagnosis of Clostridium difficile infection ( CDI). We conducted this survey to examine the effects of the new recommendations on the proportions of rejected and positive samples by the different methods. A survey was mailed to the directors of all general hospital ( GH) and health maintenance organization ( HMO) clinical microbiology laboratories. The report was divided into two periods, before and after implementation of the guidelines. Surveys were completed by 13/28 GH laboratories and 5/6 HMO laboratories. All 18 of these laboratories used C. difficile toxin ( CDT) enzyme immunoassay alone during the first period of the survey. In the second period, nine laboratories (Group A) used CDT- PCR: two of them used this method exclusively while the other seven used it to resolve most (>90%) of the discrepant results (glutamate dehydrogenase antigen ( GDH) +/ CDT−]. The other nine laboratories (Group B) used combined GDH/ CDT assay, using CDT PCR in only a minority (< 20%) of GDH+/ CDT− cases. The overall proportion of rejected samples increased from 9.5% in the first period to 13.9% in the second (p <0.001). Between the first and second periods the proportion of positive samples increased from 9.0% to 11.6% in group A laboratories (p <0.001), but decreased from 12.9% to 9.7% in group B laboratories (p <0.001). Implementation of the guidelines has resulted in a significant increase in the proportion of rejected samples and in the proportion testing positive, suggesting more appropriate test utilization and improved sensitivity in the laboratory diagnosis of CDI. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging extremely drug-resistant pathogens; blaKPC is the predominant carbapenemase in Israel. Early detection of asymptomatic rectal carriers is important for infection control purposes. We aimed to determine who among newly identified CRE rectal carriers is prone to have a subsequent clinical specimen with CRE. A matched case-control study was conducted in a tertiary care teaching hospital in Israel. Cases with a primary positive CRE rectal test and subsequent CRE clinical specimens were matched in a 1:2 ratio with CRE rectal carriers who did not develop subsequent CRE clinical specimens (controls). Matching was based on calendar time of primary CRE isolation, whether the primary CRE isolation was ≤48 h or >48 h after hospital admission, and time at risk to have a subsequent clinical specimen. Data were extracted from the patients' medical records and from the hospital's computerized database. One hundred and thirty-two newly identified CRE rectal carriers (44 cases, 88 controls) were included. The median time interval between screening and subsequent clinical specimens was 11 days (range, 3-27); 86% of the clinical specimens were classified as true infections. Independent predictors of subsequent CRE clinical specimens were: admission to the intensive care unit, having a central venous catheter, receipt of antibiotics, and diabetes mellitus. Identification of the risk factors for subsequent infections among CRE-colonized patients can be used to control modifiable risk factors and to direct empirical antimicrobial therapy when necessary. [ABSTRACT FROM AUTHOR]

The natural history of KPC-producing Klebsiella pneumoniae ( KPC KP) carriage is unknown. We aimed to examine the duration of KPC KP carriage following hospital discharge and to study the risk factors for persistent carriage. A cohort of 125 KPC KP carriers was followed monthly for between 3 and 6 months after discharge from an acute-care hospital. Rectal swabs and data were collected at baseline and at each visit. KPC KP was detected by culture and direct bla KPC PCR. Acquisition time was regarded as the earliest date of KPC KP isolation. Resolution of carriage was defined as a negative KPC KP test in at least two consecutive samples. Analyses were separated for recent (<4 months) ( REC, 75 patients) and remote (≥4 months) ( REM, 50 patients) acquisition groups. Risk factors for persistent carriage were examined by survival analyses for the REC group and by prevalence methods for the REM group. The mean age of patients was 67.5 years and 49.6% were male. Forty-six (61%) patients in the REC group and 14 (28%) in the REM group were persistent carriers (p < 0.001). A significant risk factor for persistent carriage identified in both the REC and REM groups was the presence of any catheter (p < 0.05). Unique risk factor groups included long-term care facility ( LTCF) residence (p < 0.01) and a low functional status as measured by the Barthel's index (p < 0.05) in the REC group and high Charlson's score in the REM group (p < 0.05). Out of the entire 100 patients who had at least one negative sample, only 65 remained negative on subsequent cultures. In conclusion, persistent carriage of KPC KP is associated with catheter use and a low functional status; it is more common in patients with recent acquisition and is related to LTCF stay. A single negative KPC KP test is insufficient to exclude persistent carriage. [ABSTRACT FROM AUTHOR]

The aims of our study were to analyse the risk factors for colonization by Extended-spectrum β-lactamases (ESBL)-producing Proteus mirabilis ( ESBL- PM) in rehabilitation patients and to characterize the molecular features of these strains. The study was conducted in two rehabilitation centres located in Rome, Italy ( Fondazione Santa Lucia IRCCS (FSL)), and Tel- Aviv, Israel ( Tel-Aviv Sourasky Medical Center (TASMC)). Carriage of ESBL- PM was surveyed by rectal swabs. Strain typing was performed by pulsed-field gel electrophoresis (PFGE). Identification of ESBL genes was done by PCR and sequencing. Patients admitted to the same institutions without ESBL carriage were included as controls. The study group included 70 and 41 patients from FSL and TASMC, respectively. In FSL, the multivariate analysis identified severe acute brain injury ( OR = 15, 95% CI = 3.2-69.5, p 0.001), decubitus ulcer ( OR = 3.5, 95% CI = 1.2-9.8, p 0.018) and recent treatment with quinolones ( OR = 5.7, 95% CI = 1.07-30.1, p 0.042) as independent risk factors. ESBL- PM carriers stayed longer in the hospital on average and were less likely to be discharged home. No significant risk factor was identified in TASMC. There were no similarities in PFGE types or ESBL genes between the ESBL- PM isolates from the two institutions. In both hospitals, a variety of PFGE types existed but a single ESBL type predominated, namely TEM-92 in FSL ( n = 64/70; 91%) and CTX- M-2 in TASMC ( n = 37/41; 90%). A new TEM ESBL variant, TEM-177 was identified in FSL. The clonal diversity and the predominance of a single ESBL type suggested that horizontal gene transfer played an important role in dissemination of resistance. The development of a population analysis tool that would allow tracing deeper genetic relationships is required. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: E497-E505 Abstract Increasing resistance due to the production of ESBL in Escherichia coli (ESBL- E. coli) has become a major threat to public health. Our aims were to study the incidence of ESBL- E. coli acquisition during hospitalization and the transmission rates of different ESBL- E. coli clones. This was a prospective case-control study, conducted in two geriatric rehabilitation wards in Tel-Aviv. Serial rectal cultures were collected from admission till discharge. All patient-unique ESBL- E. coli isolates were subjected to molecular typing by PFGE, MLST and determination of ESBL genes. An acquisition of ESBL- E. coli was defined as traceable when a patient with the same ST, PFGE type and ESBL gene was hospitalized in the same ward in parallel to the acquisition case. ESBL- E. colis were recovered from 125 patients out of 492 enrolled: 52 were recovered upon admission, 59 acquired ESBL- E. coli during their stay, and there was undetermined status in 14 patients. A low Norton's score was associated with acquisition (O.R. 1.14 for each point, 95% C.I. 1.01-1.29, p < 0.05). ESBL- E. coli infections ( n = 9) had occurred only in ESBL- E. coli carriers. The pandemic ST131 clone was the most common (48/125). The majority of the isolates (101/125) produced CTX-M-type ESBL. Of the 59 acquisition cases, 32 were traced to another patient. In-hospital dissemination was highest in the CTX-M-27-producing ST131 and the SHV-5-producing ST372 sub-clones (acquisition/admission ratios of 17/11 and 9/3, respectively), with almost all cases traced to other patients. In conclusion, most ESBL- E. coli acquisition cases were traceable to other patients. The transmission potential varied significantly between ESBL- E. coli clones. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: 413-431 Abstract Plasmid-acquired carbapenemases in Enterobacteriaceae, which were first discovered in Europe in the 1990s, are now increasingly being identified at an alarming rate. Although their hydrolysis spectrum may vary, they hydrolyse most β-lactams, including carbapenems. They are mostly of the KPC, VIM, NDM and OXA-48 types. Their prevalence in Europe as reported in 2011 varies significantly from high (Greece and Italy) to low (Nordic countries). The types of carbapenemase vary among countries, partially depending on the cultural/population exchange relationship between the European countries and the possible reservoirs of each carbapenemase. Carbapenemase producers are mainly identified among Klebsiella pneumoniae and Escherichia coli, and still mostly in hospital settings and rarely in the community. Although important nosocomial outbreaks with carbapenemase-producing Enterobacteriaceae have been extensively reported, many new cases are still related to importation from a foreign country. Rapid identification of colonized or infected patients and screening of carriers is possible, and will probably be effective for prevention of a scenario of endemicity, as now reported for extended-spectrum β-lactamase (mainly CTX-M) producers in all European countries. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: E164-E169 Abstract This study aimed to determine the prevalence of and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) carriage among patients newly admitted to rehabilitation centres. It is a prospective study examining MRSA carriage on admission to seven rehabilitation wards in four countries. Risk factors for MRSA carriage were analysed using univariate and multivariate analyses. A total of 1204 patients were studied. Among them, 105 (8.7%) had a positive admission MRSA screening result. The MRSA carriers were more likely to be male, to have had a recent stay in another long-term-care facility or >2 weeks acute-care hospital stay, history of colonization with MRSA, reduced level of consciousness, peripheral vascular disease and pressure sores. In multivariable logistic regression male gender (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.4-3.6, p 0.001), history of MRSA positivity (OR 6.8, 95% CI 3.8-12.3, p <0.001), peripheral vascular disease (OR 2.5, 95% CI 1.2-5, p 0.013), recent stay in another long-term-care facility (OR 2.1, 95% CI 1.3-3.5, p 0.004), or long (>2 weeks) acute-care hospital stay (OR 1.9, 95% CI 1.2-3, p 0.004), remained significant risk factors for MRSA carriage. MRSA carriage is common on admission to rehabilitation centres but less so, than previously described in long-term-care facilities. Male gender, history of MRSA positivity, previous hospitalization and peripheral vascular disease may predict MRSA carriage, and may serve as indicators for using pre-emptive infection control measures. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: 268-281 Abstract Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided. [ABSTRACT FROM AUTHOR]

In 2008, an increase in the prevalence of carbapenem-resistant Klebsiella pneumoniae was noted in a 286-bed tertiary case hospital in Colombia, where 84 patients (32 infected and 52 colonized) had positive cultures. The identified index patient came from Israel for a liver transplantation. High level carbapenem resistance was observed. Polymyxin B and tigecycline were the only two antibiotics that remained active. PCR-restriction fragment length polymorphism analysis and sequencing revealed blaKPC-3 in the major clone, which was indistinguishable from the K. pneumoniae carbapenemase-3-producing clone described previously in Israel. This exemplifies the threat posed by the global spread of K. pneumoniae carbapenemase-producing pathogens. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2010; 16: 747–752 Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with increased mortality. Delay in appropriate antimicrobial therapy (DAAT) is an important risk factor for death, although confounding between carriage of MRSA and DAAT has not been resolved. We studied the association of risk factors with mortality and searched for specific populations vulnerable to DAAT. We conducted a case–control study comparing patients with MRSA bacteraemia who died during hospitalization (cases) with patients with MRSA bacteraemia who survived (controls) in three medical centres in two states. Patients were identified using computerized hospital databases for the years 2001–2005. Medical records were retrieved and various epidemiological data extracted. Bivariate and multivariate logistic regression analyses were performed. Overall, 388 patients with MRSA bacteraemia were included, 164 cases and 224 controls. According to bivariate analyses, cases were significantly more likely than controls to (i) be older (>65 years), (ii) have transferred from an institution, (iii) have stayed in an ICU, (iv) have had more invasive devices, (v) have a poorer prognosis on admission, (vi) have higher disease severity at the time of bacteraemia, and (vii) have a DAAT of ≥2 days. Upon multivariate analysis, among patients >65 years, DAAT was significantly associated with increased mortality (p 0.04). Furthermore, patients >65 years with severe sepsis were much more likely to experience DAAT (p 0.02). In elderly patients with MRSA bacteraemia, DAAT is associated with increased mortality. Moreover, advanced age is a predictor for DAAT. These significant epidemiological associations mandate early coverage of MRSA in septic elderly patients. [ABSTRACT FROM AUTHOR]

We evaluated the sensitivity of surveillance cultures for carbapenem-resistant Acinetobacter baumannii (CRAB) in patients and in their environment. Patients with a CRAB-positive clinical culture were sampled within 7 days; the buccal mucosa and rectum were sampled using swabs, and skin was sampled using pre-moistened sterile sponges. Sponges were also used to sample the surrounding environment. Specimens were inoculated onto CHROMagar MDR Acinetobacter plates both directly and after overnight enrichment. CRAB load was scored semi-quantitatively and composite scores for patient colonization and environmental contamination were calculated. Thirty-four patients were included. Screening sensitivity was 28/34 (82%) for buccal mucosa, 30/34 (88%) for skin, and 25/34 (74%) for rectum. Combined sensitivity was 32/34 (94%). Among patients with CRAB-positive respiratory cultures, sensitivity for buccal mucosa was 20/20 (100%). Direct inoculation had excellent sensitivity: 25/28 (89%) for all three sites combined. In the subgroup of patients who did not have a respiratory source for CRAB, direct inoculation sensitivity was lower than among patients with CRAB-positive respiratory cultures: 5/8 (63%) versus 20/20 (100%). The environment of all patients was contaminated with CRAB. There was a positive correlation between the patient colonization score and the environmental contamination score (r = 0.63, p <0.001; r = 0.4, p 0.04 for buccal mucosa, r = 0.7, p <0.001 for skin, and r = 0.46, p 0.14 for rectum). In conclusion, screening for CRAB carriers can be performed by direct plating of skin and buccal mucosa samples. Environmental contamination is common and can be monitored. Implementing screening may facilitate infection control efforts to limit the spread of CRAB. [ABSTRACT FROM AUTHOR]

Antibiotic consumption is an easily quantifiable performance measure in hospitals and might be used for monitoring. We conducted a review of published studies and online surveillance reports reporting on antibiotic consumption in acute care hospitals between the years 1997 and 2013. A pooled estimate of antibiotic consumption was calculated using a random effects meta-analysis of rates with 95% confidence intervals. Heterogeneity was assessed through subgroup analysis and metaregression. Eighty studies, comprising data from 3130 hospitals, met the inclusion criteria. The pooled rate of hospital-wide consumption was 586 (95% confidence interval 540 to 632) defined daily doses (DDD)/1000 hospital days (HD) for all antibacterials. However, consumption rates were highly heterogeneous. Antibacterial consumption was highest in intensive care units, at 1563 DDD/1000 HD (95% confidence interval 1472 to 1653). Hospital-wide antibacterial consumption was higher in Western Europe and in medium-sized, private and university-affiliated hospitals. The methods of data collection were significantly associated with consumption rates, including data sources, dispensing vs. purchase vs. usage data, counting admission and discharge days and inclusion of low-consumption departments. Heterogeneity remained in all subgroup analyses. Major heterogeneity currently precludes defining acceptable antibiotic consumption ranges in acute care hospitals. Guidelines on antibiotic consumption reporting that will account for case mix and a minimal set of hospital characteristics recommending standardized methods for monitoring and reporting are needed. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: 439-448 Abstract The wide dissemination of carbapenemase-producing Gram-negatives (CPGNs), including enterobacterial species and non-fermenters, has caused a public health crisis of global dimensions. These organisms cause serious infections in hospitalized patients, and are associated with increased mortality. Cross-transmission is common, and outbreaks may occur in healthcare facilities where the infection control practices are inadequate. CPGNs exhibit extensive drug-resistant phenotypes, complicate therapy, and limit treatment options. Systematic data on therapy are limited. However, regimens combining two or more active agents seem to be more efficacious than monotherapy in carbapenemase-producing Klebsiella pneumoniae infections. Strict infection control measures, including active surveillance for timely detection of colonized patients, separation of carriers from non-carriers, and contact precautions, are of utmost importance, and may be the only effective way of preventing the introduction and transmission of these bacteria in healthcare settings. [ABSTRACT FROM AUTHOR]