Invasive meningococcal disease epidemiology and characterization of Neisseria meningitidis serogroups, sequence types, and clones; implication for use of meningococcal vaccines.

BACKGROUND AND AIMS: Neisseria meningitidis (N. meningitidis) is a Gram-negative bacterium that can cause life-threatening invasive infections referred to as invasive meningococcal disease (IMD). In the last decade the incidence of IMD in Israel is about 1/100,000 population annually. We aimed to describe the epidemiology of IMD in Israel combining epidemiological data and characterization of N. meningitidis isolates. METHODS: Invasive infection caused by N. meningitidis is a notifiable disease in Israel. Data were collected by epidemiological investigations and control measures were employed. Laboratory work-up included serogrouping, N. meningitides molecular characterization and whole-genome sequencing. RESULTS: During 1998-2017, 1349 cases of IMD were notified in Israel (mean annual incidence rate 0.94/100,000). The peak incidence rates were observed in infants under 1 year of age (10.9/100,000). Case fatality rate was 9.7%. The majority of the N. meningitidis isolates were of serogroup B (67.9%). During 2007-2017, three clonal complexes (CC) 32, 41/44 and 23 (hyper-invasive clonal complexes) were the leading CC (61%). CC32 was the leading CC causing meningococcemia and mortality. In 2017, 35 isolates were tested for 4CMenB antigens variants; of the serogroup B isolates tested 46.7% showed a match to one or more antigens (fHbp or PorA:VR1), most were ST32 (CC32). CONCLUSIONS: Preliminary analysis based on limited number of samples suggests that the 4CMenB coverage would be about half the strains; further research is necessary. Integration of clinical, epidemiological and laboratory data is essential to support decision-making on the introduction of the novel MENB vaccines in Israel.

Preoperative Hand Decontamination in Ophthalmic Surgery: A Comparison of the Removal of Bacteria from Surgeons' Hands by Routine Antimicrobial Scrub versus an Alcoholic Hand Rub.

PURPOSE: The goal of this experiment was to evaluate and compare the antimicrobial efficacy of routine preoperative hand washing using commercial medicated sponge brushes versus an alcoholic hand rub, by comparing bacterial growth on ophthalmic surgeons' hands after application of each of these methods. METHODS: Twenty ophthalmic surgeons were recruited at the Hadassah-Hebrew University Medical Center in Jerusalem, Israel. Samples were collected twice from the hands of each surgeon after hand decontamination using two different protocols during routine surgical practice. The routine preparation consisted of a 3-minute surgical scrub using commercial brush-sponges incorporating either 4% chlorhexidine gluconate (CHG) or 1% povidone-iodine (PVP-I) formulations with detergent, followed by drying the hands with a sterile towel, while the 70% ethanol solution was applied for 60-seconds and allowed to air dry. Half of the group was randomly assigned to provide samples first after the routine method and the alcoholic solution a week later, and the other half of the group was sampled in the reverse order. Viable counts of bacteria were evaluated using a modified glove juice method. Bacterial colonies were enumerated after incubation for 24 hours and expressed as colony forming units (CFU)/mL for each pair of hands. RESULTS: Geometric mean counts were 1310 and 39 CFU/mL, in the routine and alcohol rub groups, respectively, representing a mean log10 reduction in 1.53. The difference between the paired bacterial counts for the routine versus the alcohol rub was statistically significant (p < 0.0001). There was no statistically significant difference between log10 reductions for CHG and PVP-I (p = 0.97). CONCLUSIONS: This study provides evidence that an alcohol rub protocol is more effective in reducing bacterial counts on hands than routine surgical hand preparation with PVP-I and CHG in a population of practicing ophthalmic surgeons in the operative clinical setting. Thus, it provides a safe alternative as a preoperative hand disinfection method.

Trends of Bacterial Keratitis Culture Isolates in Jerusalem; a 13- Years Analysis.

PURPOSE: To describe the trends in pathogens and antibacterial resistance of corneal culture isolates in infectious keratitis during a period of 13 years at Hadassah-Hebrew University Medical Center. METHODS: A Retrospective analysis of bacterial corneal isolates was performed during the months of January 2002 to December 2014 at Hadassah Hebrew University Medical Center. Demographics, microbiological data and antibiotic resistance and sensitivity were collected. RESULTS: A total of 943 corneal isolates were analyzed during a 13 year period. A total of 415 positive bacterial cultures and 37 positive fungal cultures were recovered, representing 48% of the total cultures. The Annual incidence was 34.78 ± 6.54 cases. The most common isolate was coagulase-negative staphylococcus (32%), which had a significant decrease in trend throughout the study period (APC = -8.1, p = 0.002). Methicillin-resistant Staphylococcus aureus (MRSA) appears to have a decrease trend (APC = -31.2, P = 0.5). There was an increase in the resistance trend of coagulase-negative staphylococci to penicillin (APC = 5.0, P = <0.001). None of the pathogens had developed any resistance to Vancomycin. (P = 0.88). CONCLUSIONS: Coagulase negative staphylococci were the predominant bacteria isolated from patients with keratitis. There was no significant change in the annual incidence of cases of bacterial keratitis seen over the past 13 years. Keratitis caused by MRSA appeared to decrease in contrast to the reported literature.

Trends in the Epidemiology of Campylobacteriosis in Israel (1999-2012).

The objective of this study was to examine the recent trends in the epidemiology of campylobacteriosis in Israel. A Sentinel Laboratory-Based Surveillance Network for Bacterial Enteric Diseases was established in Israel by the Israel Center for Disease Control (ICDC). This network generated data on subjects from whom Campylobacter spp. was isolated in community and hospital laboratories. Further characterization of the isolates was done at the Campylobacter National Reference Laboratory. Data from these two sources were integrated and analyzed at the ICDC. Between 1999 and 2012, 40,978 Campylobacter stool isolates were reported to the ICDC by the sentinel laboratories. The incidence rate of campylobacteriosis increased from 65.7 per 100,000 in 1999 to 101.7 per 100,000 in 2012. This increase resulted from a significant rise in the incidence of campylobacteriosis in the Jewish population which, since 2009, surpassed the consistent higher incidence of the disease in Israeli Arabs. The peak morbidity in Israel consistently occurred in late spring, with a risk excess in males compared with females, in younger age groups and earlier in the life span among Arabs than among Jews and others. These results suggest that further analytical studies should be carried out to identify risk factors responsible for the increased incidence of campylobacteriosis and better direct prevention and control of the disease in Israel.

Cost-utility analysis of a nationwide vaccination programme against serogroup B meningococcal disease in Israel.

OBJECTIVES: Using cost-utility analysis, to evaluate whether or not to adopt a Neisseria meningitidis serogroup B vaccination programme for Israeli children. METHODS: Epidemiological, demographic, health service utilisation and economic data were integrated into a spreadsheet model to calculate the cost per averted disability-adjusted life year (DALY) of the intervention. RESULTS: Assuming 78 % vaccine efficacy with no herd immunity, vaccination will prevent 223 cases and 22 deaths over a 100-year period. Based on vaccine price of $60 per dose, total intervention costs ($315,400,000) are partially offset by a $22,700,000 reduction in treatment and sequelae costs as a result of decreased morbidity. The intervention was not cost-effective since the net cost ($292,700,000) per averted DALY gained (1249 mostly due to decreased mortality) was $234,394. Additional two dose catch-up programmes vaccinating children in cohorts aged 1-2 to 1-13 were also not cost-effective. CONCLUSIONS: The vaccination will become cost-effective if vaccine costs fall below $19.44 per dose. However, in identified high risk areas, the vaccine would be cost-effective and could be recommended for use both with and without catch-up campaigns.

Reduction in incidence of invasive fungal infection in patients receiving allogeneic stem cell transplantation using combined diagnostic-driven approach and itraconazole oral solution.

Invasive fungal infections are an important cause of morbidity and mortality after allogeneic haematopoietic stem cell transplantation. We evaluated, in our allogeneic stem cell transplant patients, the effect on the incidence of invasive fungal infection during neutropenia of a strategy combining a diagnostic-driven approach with chemoprophylaxis during higher risk periods of graft vs. host disease and prolonged neutropenia, using itraconazole oral solution with parenteral voriconazole bridging. One hundred and thirty patients admitted for allogeneic stem cell transplantation within two predefined 20 month periods were included in the study. Data for all patients were collected prospectively. Implementation of the protocol resulted in the administration of more prophylactic antifungals to more patients. Following implementation, there was a non-significant decrease in the overall number of invasive fungal infections (IFI) [11 of 65 patients (17.2%) vs. 4 of 65 patients (6.2%, P = 0.051)], as well as in the occurrence of invasive mould infections [8 of 65 patients (12.5%) vs. 2 of 65 patients (3.1%, P = 0.054)]. Survival rates at three and 6 months were not significantly affected. A combined diagnostic-driven approach and antifungal prophylaxis with oral itraconazole and an intravenous voriconazole bridging protocol, was associated with a reduced, albeit non-statistically significant, number of IFI in our medical centre.

A national survey of the molecular epidemiology of Clostridium difficile in Israel: the dissemination of the ribotype 027 strain with reduced susceptibility to vancomycin and metronidazole.

Our goals were to study the molecular epidemiology and antimicrobial susceptibilities of C. difficile strains in Israel. Microbiology laboratories serving 6 general hospitals (GH) and 10 long-term care facilities (LTCF) were asked to submit all stool samples in January-February 2014 that tested positive for C. difficile. Toxigenic C. difficile isolates were recovered in 208 out of 217 samples (95.8%), of which 50 (23.6%) were from LTCFs. Ribotype 027 was the most common type overall, identified in 65 samples (31.8%), and was the predominant strain in the 3 GHs with the highest incidence of C. difficile infections. Other common strains were slpA types cr-02 (n = 45) and hr-02 (n = 18). The proportions of vancomycin and metronidazole MIC values >2mg/L were high in ribotype 027 (87.7% and 44.6%, respectively) and slpA-cr-02 strains (88.8% and 17.8%, respectively). This study demonstrates that the ribotype 027 strain has disseminated across Israel and is now the most common strain.

False negative ß-2 transferrin in the diagnosis of cerebrospinal fluid leak in the presence of Streptococcus pneumoniae.

OBJECTIVES/HYPOTHESIS: The objectives of this study were to examine the presence of ß-2 transferrin (ß2TRNSF) in cerebrospinal fluid (CSF) contaminated in vitro by various bacteria and explore the mechanism (passive or active) responsible for ß2TRNSF elimination. Early diagnosis of CSF leakage may change treatment decisions and minimize the risk of meningitis and encephalitis. ß2TRNSF is a protein present exclusively in CSF. Its detection is highly useful in cases of CSF leakage, although it has never been examined in the presence of central nervous system infection. STUDY DESIGN: Prospective patient analysis. METHODS: Sterile CSF drawn from patients was contaminated in vitro with several microorganisms chosen for their ability to cause neurosurgical-related infections: Streptococcus pneumoniae, methicillin-sensitive Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. ß2TRNSF was examined at two time points: following immediate inoculation (t0) and following an overnight incubation (t18) over various bacterial concentrations. Samples of CSF inoculated with S pneumoniae were also examined in the presence of ciprofloxacin. For ß2TRNSF analysis we used immunoblotting electrophoresis and enzyme-linked immunosorbent assay (ELISA). RESULTS: CSF samples collected from nine patients were analyzed. ß2TRNSF was not detected following S pneumoniae inoculation at both time points when immunoblotting electrophoresis was used. Quantitative analysis using ELISA demonstrated significant ß2TRNSF concentration decrease. The addition of ciprofloxacin led to the same results. CONCLUSIONS: CSF leak detection using ß2TRNSF may be deceiving in the presence of a S pneumoniae cerebral nervous system infection. A passive process is suggested, as ß2TRNSF disappeared either immediately or following incubation with inactive bacteria.

Pregnancy-associated listeriosis: clinical characteristics and geospatial analysis of a 10-year period in Israel.

BACKGROUND: Listeria monocytogenes is a foodborne pathogen that causes life-threatening infections in elderly, immunocompromised, and pregnant women. In pregnancy it may cause fetal loss or a preterm delivery, and the neonate is prone to neonatal sepsis and death. METHODS: We created a cohort of all L. monocytogenes cases during 10 years (1998-2007) in Israel, by a comprehensive review of cases in hospitals throughout the country and cases reported to the Ministry of Health. RESULTS: One hundred sixty-six pregnancy-related listeriosis cases were identified, resulting in a yearly incidence of 5-25 cases per 100 000 births. Presentation associated with fetal demise was more common in the second trimester (55.3%), and preterm labor (52.3%) and abnormal fetal heart rate monitoring (22.2%) were more common in the third trimester (P = .001). Fetal viability was low in the second trimester (29.2%) and much higher (95.3%) in the third trimester. Each additional week of pregnancy increased the survival chance by 33% (odds ratio, 1.331 [95% confidence interval, 1.189-1.489]). A single case of maternal mortality was identified. Listeria monocytogenes serotype 4b was more common in pregnancy-related than in non-pregnancy-related cases (79.5% vs 61.3%, P = .011). Pulsed-field gel electrophoresis analysis suggested that 1 pulsotype is responsible for 35.7% of the pregnancy cases between 2001 and 2007. This clone is closely related to the Italian gastroenteritis-associated HPB2262 and the invasive US Scott A L. monocytogenes strains. CONCLUSIONS: Our survey emphasizes the high rate of pregnancy-related listeriosis in Israel and shows that specific clones might account for this.

Contamination of hypertonic saline solutions in use by cystic fibrosis patients in Israel.

BACKGROUND: Treatment of cystic fibrosis (CF) patients with inhaled hypertonic saline (HS) solutions is safe, beneficial and reduces exacerbation rates. We studied contamination of solutions used by Israeli CF patients for prolonged periods. METHODS: The study addressed whether daily opening of previously unopened solutions caused contamination, survival of 6 CF-associated bacteria in artificially inoculated solutions, in-use contamination of solutions and patterns of their use by patients. RESULTS: Repeated opening did not contaminate solutions and survival of indicator bacteria was variable. Mycobacterium abscessus survived in 3% HS solution for 6 weeks and Burkholderia cenocepacia and Pseudomonas aeruginosa were longer. In 30/76 (39.5%) of used solutions 49 contaminants were found, none being common CF-associated pathogens. CONCLUSIONS: Most CF-related bacteria survived to some degree in HS. Approximately 40% of solutions used by patients were contaminated by organisms of uncertain significance. Our findings highlight the potential risk posed by contamination of HS solutions and support recommendations to use sterile unit-dose formulations.

Draft Genome Sequence of a Meningitic Isolate of Cronobacter sakazakii Clonal Complex 4, Strain 8399.

The Cronobacter sakazakii clonal lineage defined as clonal complex 4 (CC4), composed of nine sequence types, is associated with severe cases of neonatal meningitis. To date, only closely related C. sakazakii sequence type 4 (ST4) strains have been sequenced. C. sakazakii strain 8399, isolated from a case of neonatal meningitis, was sequenced as the first non-ST4 C. sakazakii strain.

Interactions between Scenedesmus and Microcystis may be used to clarify the role of secondary metabolites.

Microcystis sp. are major players in the global intensification of toxic cyanobacterial blooms endangering the water quality of freshwater bodies. A novel green alga identified as Scenedesmus sp., designated strain huji (hereafter S. huji), was isolated from water samples containing toxic Microcystis sp. withdrawn from Lake Kinneret (Sea of Galilee), Israel, suggesting that it produces secondary metabolites that help it withstand the Microcystis toxins. Competition experiments suggested complex interaction between these two organisms and use of spent cell-free media from S. huji caused severe cell lysis in various Microcystis strains. We have isolated active metabolites from the spent S. huji medium. Application of the concentrated allelochemicals interfered with the functionality and perhaps the integrity of the Microcystis cell membrane, as indicated by the rapid effect on the photosynthetic variable fluorescence and leakage of phycobilins and ions. Although some activity was observed towards various bacteria, it did not alter growth of eukaryotic organisms such as the green alga Chlamydomonas reinhardtii.

Vaccination, herd behavior, and herd immunity.

BACKGROUND: During the 2009 outbreak of novel influenza AH1N1, insufficient data were available to adequately inform decision makers about benefits and risks of vaccination and disease. We hypothesized that individuals would opt to mimic their peers, having no better decision anchor. We used Game Theory, decision analysis, and transmission models to simulate the impact of subjective risks and preference estimates on vaccination behavior. METHODS: We asked 95 students to provide estimates of risk and health state valuations with regard to AH1N1 infection, complications, and expectations of vaccine benefits and risks. These estimates were included in a sequential chain of models: a dynamic epidemic model, a decision tree, and a population-level model. Additionally, participants' intentions to vaccinate or not at varying vaccination rates were documented. RESULTS: The model showed that at low vaccination rates, vaccination dominated. When vaccination rates increased above 78%, nonvaccination was the dominant strategy. We found that vaccination intentions did not correspond to the shift in strategy dominance and segregated to 3 types of intentions: regardless of what others do 29/95 (31%) intended to vaccinate while 27/95 (28%) did not; among 39 of 95 (41%) intention was positively associated with putative vaccination rates. CONCLUSIONS: Some people conform to the majority's choice, either shifting epidemic dynamics toward herd immunity or, conversely, limiting societal goals. Policy leaders should use models carefully, noting their limitations and theoretical assumptions. Behavior drivers were not explicitly explored in this study, and the discrepant results beg further investigation. Models including real subjective perceptions with empiric or subjective probabilities can provide insight into deviations from expected rational behavior and suggest interventions in order to provide better population outcomes.

[The effect of an intervention on rates of central vascular catheter-related bloodstream infection in intensive care units at the Hadassah Medical Center].

INTRODUCTION: Catheter-related bloodstream infection (CR-BSI) is a significant source for morbidity and mortality in addition to increased hospital costs. Patients in intensive care units (ICUs) have a greater risk for CR-BSI. Continuous monitoring and control of intravascular central catheters insertion (CCI) by using checklists have a key role in reducing the rate of infections and improving patient health care quality and safety. OBJECTIVES: To determine the rate of CR-BSI, and to evaluate the adherence of ICU teams to infection control guidelines during CCI prior to and following an intervention program in ICU patients. METHODS: The present study was conducted in six ICUs at the Hadassah Medical Center, during a period of 15 months. The rate of CR-BSI was determined in 320 patients with central catheters during the first period of the study. Assessment of adherence to infection control guidelines during CCI was carried out by observations. Educational intervention consisted of the introduction of physician guidelines for CCI, implementing a checklist to ensure adherence to the guidelines and lectures for the teams, beginning in the second period of the study. During the third period of the study, the rate of CR-BSI was determined in 336 patients with central catheters in the same ICUs, by the same research methods. RESULTS: Following the intervention, a significant reduction in the rate of CR-BSI was observed in the study population from 9.66 to 3.63 infections per 1000 catheter days, with 62.4% risk reduction for CR-BSI, (P < 0.001). Improvements were also recorded in the CCI process and the rate of compliance of the ICUs team with infection control guidelines. CONCLUSIONS: The implementation of a simple and inexpensive intervention reduced the rate of CR-BSI, leading to improved process of insertion of these catheters. DISCUSSION: The continuous monitoring of the rate of CR-BSI and using checklists in every CCI process may reduce the morbidity, mortality, hospital stay, and lower hospital costs associated with centrally placed vascular catheters.

Continuous surveillance to reduce extended-spectrum ß-lactamase Klebsiella pneumoniae colonization in the neonatal intensive care unit.

BACKGROUND: Clinical illness caused by resistant bacteria usually represents a wider problem of asymptomatic colonization. Active surveillance with appropriate institution of isolation precautions represents a potential mechanism to control colonization and reduce infection. The neonatal intensive care unit (NICU) is an environment particularly appropriate for such interventions. Neonates are rarely colonized by resistant bacteria on admission and staff enthusiasm for infection control is high. OBJECTIVE: To reduce extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (ESBL-KP) acquisition amongst neonates through a continuous active surveillance intervention. METHODS: Fecal ESBL-KP cultures were performed weekly on all neonates over 4 years. Neonates with positive cultures were managed with contact precautions by dedicated nurses separately from other neonates. ESBL-KP acquisition amongst neonates staying >7 days was compared for the consecutive years. A subset of ESBL-KP isolates was typed with pulsed-field gel electrophoresis (PFGE). RESULTS: Surveillance cultures were obtained from 1,482/1,763 (84%) neonates over 4 years. ESBL-KP acquisition decreased continuously from 94/397 (24%) neonates in 2006 to 33/304 (11%) in 2009 (p < 0.001, hazard ratio 0.75, 95% confidence interval 0.66-0.85, p < 0.001 for comparison of years). Hospital-wide ESBL-KP acquisition did not decrease outside the NICU. PFGE identified identical ESBL-KP strains from multiple neonates on six occasions and different strains from single neonates on seven occasions. CONCLUSIONS: ESBL-KP is probably both imported into and spread within the NICU. Continuous long-term surveillance with cohorting was associated with a decrease in ESBL-KP acquisition within the NICU. This low-risk intervention should be considered as a means to decrease neonatal acquisition of resistant bacteria.

KPC-9, a novel carbapenemase from clinical specimens in Israel.

A bla(KPC-9) carbapenemase variant was discovered in isolates of Klebsiella pneumoniae and Escherichia coli from a single patient. It differed from bla(KPC-3) by one amino acid substitution (Val239Ala). The K. pneumoniae isolate was typed as ST258, as was the epidemic Israeli KPC-3 clone. bla(KPC-9) was found on a plasmid indistinguishable from pKpQIL that carries bla(KPC-3) in the epidemic clone. Compared to KPC-3, KPC-9 conferred less resistance to carbapenems and higher resistance to ceftazidime.

Comparison of two carbapenem-resistant Klebsiella pneumoniae clones: from a contained outbreak in a paediatric population and from a national epidemic.

OBJECTIVES: A refractory epidemic of carbapenem-resistant Klebsiella pneumoniae (CRKP) emerged in the adult population at our hospital in 2005, as in most Israeli hospitals. Contemporaneously, a different clone of CRKP caused an easily contained outbreak in a paediatric long-term care facility (LTCF) in Jerusalem. While previously identified host-related risk factors for colonization by these organisms undoubtedly contributed to these outbreaks, it is very likely that bacterial factors might be crucial in explaining the striking differences in transmissibility between the implicated strains. We therefore sought bacterial factors associated with these different epidemiological behaviours. METHODS: Seven CRKP isolated at our hospital and the LTCF during 2008-09 were examined by antimicrobial susceptibility testing and PFGE, and further analyses of these two clones was done using multilocus sequence typing and competition experiments. Plasmids were analysed by conjugation, restriction mapping, PCR and sequencing. RESULTS: Both clones were multidrug resistant and harboured identical plasmids carrying the bla(KPC-3) gene. The hyper-transmissible epidemic clone carried additional antibiotic resistance genes and hosted an additional plasmid. The clone from the LTCF did not demonstrate hyper-transmissible properties despite its presence in an institution of a type commonly plagued by the epidemic clone. Competition assays showed the more easily contained strain to be fitter. CONCLUSIONS: These findings suggest that neither the presence of the plasmid carrying the bla(KPC-3) gene nor relative survival fitness account for the hyper-transmissibility of the epidemic strain. The role of patient age in susceptibility to colonization by the epidemic strain should be investigated.

Training laboratory technicians from the Ethiopian periphery in the MODS technique enables rapid and low-cost diagnosis of Mycobacterium tuberculosis infection.

Tuberculosis (TB) is a leading cause of morbidity and mortality and is frequently complicated by emergence of drug-resistant strains. Diagnosis of TB in developing countries is often based on the relatively insensitive acid-fast staining that does not enable susceptibility profiling. Microscopic observation drug susceptibility assay (MODS) is an inexpensive, simple method that enables rapid TB culture coupled with susceptibility testing. A 3-week MODS training of three Ethiopian laboratory technicians was conducted at Hadassah-Hebrew University Medical Center, Israel. Results of the trainee readings were blindly assessed by an experienced instructor. Two hundred fifty-five (255) trainee culture readings were evaluated throughout the course. The sensitivity and specificity were 75-100% and 31.5-100%, respectively. Multivariate analysis revealed that sensitivity and duration of incubation were positively correlated, although specificity was positively correlated with the length of training. MODS can be reliably performed by laboratory technicians inexperienced in culture techniques in developing countries, with high sensitivity and specificity reached after a brief learning period.

Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection.

Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole-resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.

Serum levels of anti-streptolysin O antibodies: their role in evaluating rheumatic diseases.

BACKGROUND: Family physicians measure serum levels of anti-streptolysin O antibodies (ASO) in the routine evaluation of patients with rheumatic conditions. AIM: To evaluate the significance of elevated serum ASO titer in hospitalized patients with various clinical conditions. PATIENTS AND METHODS: We retrieved the names of all patients in whom ASO serum titer was tested in our hospital during two successive years. We chose only those with titers of 1 : 160 or greater (cut-off level < 1 : 80) or with no titer. Their charts were reviewed and the causes for their hospitalization and the reasons for requesting the tests were identified. We also measured the ASO serum titer in 60 healthy individuals. RESULTS: Six hundred and twenty-five patients were tested for ASO serum levels; 129 patients were negative. In 291 (44%) patients tests were positive at low titers (< 1 : 160). In 205 (33%) the serum titers of ASO were ≥ 1 : 160. We analyzed two groups: those with high ASO titers (≥ 1 : 160) (group 1) and those who were negative for this test (group 2). In group 1, streptococcal cultures were positive only in 14% of the patients with elevated ASO. There was no correlation between ASO serum levels and erythrocyte sedimentation rate, C-reactive protein or rheumatoid factor. In only five individuals (8%) of the healthy cohort, was ASO significantly elevated. CONCLUSIONS: Elevated ASO titers can be found in various clinical conditions other than the typical post-streptococcal associated diseases. In these cases it is not necessarily accompanied by positive culture and does not correlate with inflammatory parameters.