Phenotypic and genotypic analysis of antimicrobial resistance and population structure of gastroenteritis-related Aeromonas isolates.

BACKGROUND: The population structure and the correlation between antimicrobial resistance (AMR) phenotypes and genotypes in Aeromonas species isolated from patients with gastroenteritis are not well understood. The aims of the study were to: (1) investigate the antimicrobial susceptibility profiles of Aeromonas species isolated from patients with gastroenteritis; (2) explore the relationship between AMR genes and resistance phenotypes; and (3) describe the population structure of these isolates and provide evidence of transmission events among them. METHODS: This microbiological survey was performed at the Microbiology Laboratory of the Emek Medical Center in Afula, Israel. Cultivation of Aeromonas was attempted from stool samples that tested positive by PCR. Antimicrobial susceptibility testing (AST) was performed using the Sensititre GN3F microdilution panel. Whole genome sequencing (WGS) was done using the Illumina NextSeq500/550 system. Phylogenetic studies involved multi-locus sequence typing (MLST) and core genome (cg) MLST. Resistance mechanisms were identified using the Comprehensive Antibiotic Resistance Database and compared with the AST results. RESULTS: The study included 67 patient-unique isolates. The species that were identified included A. caviae (n = 58), A. dhakensis (n = 3), A. media (n = 2), A. veronii (n = 2) and A. hydrophila (n = 2). Isolates were almost uniformly susceptible to amikacin, gentamicin, aztreonam, cefepime, ceftazidime, ciprofloxacin and meropenem. All isolates with the exception of 1-2 isolates were resistant to ampicillin, cefazolin and ampicillin-sulbactam which was compatible with the presence of the blaOXA genes. Variable resistance rates were observed to cefuroxime, cefoxitin, ceftriaxone, piperacillin-tazobactam that were not correlated with the presence of other ß-lactamase genes. Resistance to tetracycline and trimethoprim-sulfamethoxazole correlated with the presence of tetA and sul1, respectively. The population structure of A. caviae was highly diverse with the minority of the isolates (16/57) clustering into six defined sequence types. A cgMLST-based distance of four genes was found in one pair of isolates, suggesting common source transmission. CONCLUSIONS: A. caviae is the dominant species related to gastroenteritis and is characterized by a diverse population structure, with almost no evidence for common-source transmission. Resistance rates to most antimicrobial agents were low and partially matched with the presence of resistance genes.

Dual anti-viral treatment for persistent COVID-19 in immunocompromised hemato-oncological patients is associated with a favorable prognosis and minor side effects.

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19. Fifteen patients with a history of lymphoma, CLL, and MM were included. Eight were male, median age was 74. All patients had an immediate clinical and virological response. In 73 % of patients, PCR for SARS-CoV-2 became negative at the end of treatment and the rest had an increase in PCR cycle threshold (CT) values, with a median increase of 6 cycles. After a follow-up of three months, 60 % of patients remained in full clinical and virological remission. None required invasive mechanical ventilation or died. The side effects we observed, neutropenia, lactatemia and elevated transaminases, were mild and almost all transient in nature. We conclude that dual anti-viral treatment appears to be a valid treatment option for persistent COVID-19.

Molecular features and transmission of NDM-producing Enterobacterales in Israeli hospitals.

OBJECTIVES: NDM-producing Enterobacterales (NDME) account for 34.9% of new carbapenemase-producing Enterobacterales cases in Israeli hospitals. The goals of this study were to characterize the genomic composition of NDME isolates and mobile genetic elements (MGEs) and to identify NDME transmission events (TEs). METHODS: The study was conducted at the Tel-Aviv Sourasky, Rambam and Sha'are-Zedek Medical Centers (TASMC, RMC and SZMC, respectively). All NDME isolates detected between January 2018 and July 2019 were included.Phylogenetic analysis was based on core-genome SNP distances. Core-genome distance of ≤5 SNPs between isolates from patients with overlapping hospitalization periods was suggestive of a potential TE. MGEs were classified by comparison of the blaNDM gene flanking regions. RESULTS: The study included 212 NDME isolates from 203 patients, including 104 isolates from TASMC, 30 isolates from RMC and 78 isolates from SZMC. The majority of isolates (n = 157; 74%) harboured the blaNDM-1 gene, followed by the blaNDM-5 (n = 48) and blaNDM-15 genes (n = 7). The most common NDME species were Klebsiella pneumoniae (n = 67), Escherichia coli (n = 65) and Enterobacter cloacae (n = 45), all showing a highly diverse clonal structure. Most blaNDM-1-harbouring isolates (134/157; 85%) were divided into nine different MGE modules, variably distributed across species and hospitals.The numbers of post-admission acquisition cases (n = 118) that could be linked to other cases by both molecular and epidemiological criteria were 13/58 (24.2%), 3/48 (6.3%) and 4/12 (33.3%) in TASMC, SZMC and RMC, respectively. CONCLUSIONS: The study depicted a complex and diverse population structure, suggesting that NDME had not spread via clonal expansion.

Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species.

BACKGROUND: Antimicrobial resistance is common in Nocardia species but data regarding the molecular mechanisms beyond their resistance traits are limited. Our study aimed to determine the species distribution, the antimicrobial susceptibility profiles, and investigate the associations between the resistance traits and their genotypic determinants. METHODS: The study included 138 clinical strains of Nocardia from nine Israeli microbiology laboratories. MIC values of 12 antimicrobial agents were determined using broth microdilution. WGS was performed on 129 isolates of the eight predominant species. Bioinformatic analysis included phylogeny and determination of antimicrobial resistance genes and mutations. RESULTS: Among the isolates, Nocardia cyriacigeorgica was the most common species (36%), followed by Nocardia farcinica (16%), Nocardia wallacei (13%), Nocardia abscessus (9%) and Nocardia brasiliensis (8%). Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%). Resistance to other antibiotics was species-specific, often associated with the presence of resistance genes or mutations: (1) aph(2″) in N. farcinica and N. wallacei (resistance to tobramycin); (ii) blaAST-1 in N. cyriacigeorgica and Nocardia neocaledoniensis (resistance to amoxicillin/clavulanate); (iii) blaFAR-1 in N. farcinica (resistance to ceftriaxone); (iv) Ser83Ala substitution in the gyrA gene in four species (resistance to ciprofloxacin); and (v) the 16S rRNA m1A1408 methyltransferase in N. wallacei isolates (correlating with amikacin resistance). CONCLUSIONS: Our study provides a comprehensive understanding of Nocardia species diversity, antibiotic resistance patterns, and the molecular basis of antimicrobial resistance. Resistance appears to follow species-related patterns, suggesting a lesser role for de novo evolution or transmission of antimicrobial resistance.

Mpox proctitis as a likely predisposing factor for chlamydial perihepatitis in a male patient.

Perihepatitis (Fitz-Hugh-Curtis syndrome) is a rare complication of sexually transmitted infections, mostly seen in women. Only 12 male cases have been reported to date, of which Chlamydia trachomatis was confirmed in 2. We report a case of chlamydial perihepatitis in a male patient, occurring 1 month after Mpox and associated with the unusual LGV ST23 strain. Our case suggests that rectal Mpox lesions may facilitate chlamydial dissemination.

Clinical and molecular features of NDM-producing Acinetobacter baumannii in a multicenter study in Israel.

BACKGROUND: NDM-producing Acinetobacter baumannii (NDMAb) were reported sporadically worldwide but little is known about the transmission, epidemiology and clinical features of NDMAb-infected patients. The goals of this study were to characterize (1) the epidemiology and clinical features of NDMAb-infected patients; (2) the microbiological and molecular features of NDMAb isolates and (3) the transmission networks of NDMAb within healthcare facilities. METHODS: The study was conducted at the Tel-Aviv Sourasky, Rambam and Sha'are-Zedek Medical centers (TASMC, RMC and SZMC, respectively) in Israel. All cases detected between January 2018 and July 2019 were included. Phylogenetic analysis was based on core genome SNP distances. Clonal transmission was defined according to molecular (≤ 5 SNP) and epidemiological criteria (overlapping hospital stay). NDMAb cases were compared at a ratio of 1:2 with non-NDM carbapenem-resistant A. baumannii (CRAb) cases. RESULTS: The study included 54 NDMAb-positive out of 857 CRAb patients, including 6/179 (3.3%) in TASMC, 18/441 (4.0%) in SZMC and 30/237 (12.6%) in RMC. Patients infected by NDMAb had similar clinical features and risk factors as patients with non-NDM CRAb. The length-of-stay was higher in NDMAb cases (48.5 days vs. 36 days, respectively, p = 0.097) and the in-hospital mortality was similarly high in both groups. Most isolates (41/54, 76%) were first detected from surveillance culture. The majority of isolates harbored the blaNDM-2 gene allele (n = 33), followed by the blaNDM-1 (n = 20) allele and the blaNDM-4 allele (n = 1). The majority of isolates were related within the ST level to other isolates in SZMC and RMC: 17/18 and 27/30 isolates, respectfully. The common ST's were the blaNDM-1 harboring ST-2 (n = 3) and ST-107 (n = 8) in SZMC and the blaNDM-2 harboring ST-103 in SZMC (n = 6) and in RMC (n = 27). All blaNDM alleles were located within a conserved mobile genetic environment flanked by the ISAb125 and IS91 family transposon. Clonal transmission was identified in most hospital-acquired cases in RMC and SZMC. CONCLUSION: NDMAb constitutes a minor part of CRAb cases and are clinically similar to non-NDM CRAb. Transmission of NDMAb occurs mostly by clonal spread.

Evolution of spike mutations following antibody treatment in two immunocompromised patients with persistent COVID-19 infection.

Immunocompromised patients have an increased risk of persistent COVID-19 disease. We report here the clinical course of two patients with hematologic malignancies hospitalized due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In both patients, viral evolution including new spike gene mutations that occurred following treatment with anti-SARS-CoV-2 antibodies preparations, including convalescent plasma and bamlanivimab. These cases demonstrate the possibility of antibody-resistant SARS-CoV-2 infections evolution in immunocompromised patients.

Emergence of Mycobacterium canariasense infections in central Israel.

In 2018, Mycobacterium canariasense bloodstream infection was diagnosed in Israel. Further investigation had identified additional five cases in three medical centers, including isolates from blood (1), cornea (1), and sputum (3). Isolates were susceptible to all the antimicrobial tested. All but one isolate was related by whole-genome phylogeny.

Clinical features and outcomes of bacteremic and non-bacteremic Campylobacteriosis: a case-control study.

PURPOSE: Campylobacter bloodstream infection (C-BSI) is uncommon, and its clinical significance is unclear. The aim of the study was to determine risk factors and clinical outcomes associated with Campylobacter BSI. METHODS: We performed a single center retrospective case-control study comparing patients with C-BSI (cases) and patients with nonbacteremic Campylobacter enteritis (controls), from January 2007 through June 2020. Case and control patients were matched by age and sex at a ratio of 1:2. Demographic, clinical, and microbiological characteristics were compared between groups. RESULTS: We identified 76 patients with C-BSI and matched them with 149 nonbacteremic patients with Campylobacter enteritis. Rates of C-BSI increased tenfold in 2014 following the introduction of BacTAlert FA/FN Plus blood culture bottles. Baseline variables significantly associated with C-BSI on multivariable logistic regression were fever, absence of diarrhea and recent exposure to antibiotics. Compared with controls, C-BSI was associated with higher 30-day mortality (12% vs. 2%, P = 0.003), more frequent need for intensive care (6.6% vs. 1.2%, P = 0.032) and longer hospital stay (median, 5 days vs. 3 days, P = 0.003). There was a high proportion of immunocompromised patients in both groups (55%). CONCLUSIONS: C-BSI is identified with increasing frequency, reflecting both changes in epidemiology and improved sensitivity of blood culture systems. Our findings indicate that detection of Campylobacter spp. in blood culture is associated with significantly higher rates of death and other adverse outcomes.

C-reactive protein velocity discriminates between acute viral and bacterial infections in patients who present with relatively low CRP concentrations.

BACKGROUND: To assess the utility of C-reactive protein (CRP) velocity to discriminate between patients with acute viral and bacterial infections who presented with relatively low CRP concentrations and were suspected of having a bacterial infection. METHODS: We analyzed a retrospective cohort of patients with acute infections who presented to the emergency department (ED) with a relatively low first CRP measurement (CRP1) ≤ 31.9 mg/L and received antibiotics shortly after. We then calculated C-reactive protein velocity (CRPv), milligram per liter per hour, for each patient based on CRP1 and the second CRP value (CRP2) measured within the first 24 h since admission. Finally, we compared CRPv between patients with bacterial and viral infections. RESULTS: We have presently analyzed 74 patients with acute bacterial infections and 62 patients with acute viral infections at the mean age of 80 and 66 years respectively, 68 male and 68 female. CRP1 did not differ between both groups of patients (16.2 ± 8.6 and 14.8 ± 8.5 for patients with viral and bacterial infections respectively, p value = 0.336). However, the CRP2 was significantly different between the groups (30.2 ± 21.9 and 75.6 ± 51.3 for patients with viral and bacterial infections respectively, p-value < 0.001) and especially the CRPv was much higher in patients with acute bacterial infections compared to patients with acute viral infections (0.9 ± 1.2 and 4.4 ± 2.7 respectively, p-value < 0.001). CONCLUSION: CRPv and CRP2 are useful biomarkers that can discriminate significantly between patients who present with acute bacterial and viral infections, and relatively low CRP concentration upon admission who were suspected of having a bacterial infection.

Excluded versus included patients in a randomized controlled trial of infections caused by carbapenem-resistant Gram-negative bacteria: relevance to external validity.

BACKGROUND: Population external validity is the extent to which an experimental study results can be generalized from a specific sample to a defined population. In order to apply the results of a study, we should be able to assess its population external validity. We performed an investigator-initiated randomized controlled trial (RCT) (AIDA study), which compared colistin-meropenem combination therapy to colistin monotherapy in the treatment of patients infected with carbapenem-resistant Gram-negative bacteria. In order to examine the study's population external validity and to substantiate the use of AIDA study results in clinical practice, we performed a concomitant observational trial. METHODS: The study was conducted between October 1st, 2013 and January 31st, 2017 (during the RCTs recruitment period) in Greece, Israel and Italy. Patients included in the observational arm of the study have fulfilled clinical and microbiological inclusion criteria but were excluded from the RCT due to receipt of colistin for > 96 h, refusal to participate, or prior inclusion in the RCT. Non-randomized cases were compared to randomized patients. The primary outcome was clinical failure at 14 days of infection onset. RESULTS: Analysis included 701 patients. Patients were infected mainly with Acinetobacter baumannii [78.2% (548/701)]. The most common reason for exclusion was refusal to participate [62% (183/295)]. Non-randomized and randomized patients were similar in most of the demographic and background parameters, though randomized patients showed minor differences towards a more severe infection. Combination therapy was less common in non-randomized patients [31.9% (53/166) vs. 51.2% (208/406), p = 0.000]. Randomized patients received longer treatment of colistin [13 days (IQR 10-16) vs. 8.5 days (IQR 0-15), p = 0.000]. Univariate analysis showed that non-randomized patients were more inclined to clinical failure on day 14 from infection onset [82% (242/295) vs. 75.5% (307/406), p = 0.042]. After adjusting for other variables, non-inclusion was not an independent risk factor for clinical failure at day 14. CONCLUSION: The similarity between the observational arm and RCT patients has strengthened our confidence in the population external validity of the AIDA trial. Adding an observational arm to intervention studies can help increase the population external validity and improve implementation of study results in clinical practice. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01732250 on November 22, 2012.

Multiplex lateral flow immunochromatographic assay is an effective method to detect carbapenemases without risk of OXA-48-like cross reactivity.

BACKGROUND: It is essential to detect carriers of carbapenemase-producing Enterobacterales in order to implement infection control measures. The objectives of this study was to evaluate the NG-Test® CARBA 5 (CARBA 5) assay for detection of five carbapenemases and to assess the cross reactivity of other OXA-type carbapenemases with the OXA-48-like specific antibodies. METHODS: A total of 197 Enterobacterales isolates were tested. To evaluate the cross reactivity, 73 carbapenem-resistant A. baumannii, harboring OXA-type variants, were tested. Polymerase chain reaction (PCR) served as gold standard for carbapenemase identification. RESULTS: Excellent agreement was found between PCR and CARBA 5, for all but one isolate. The single false positive result (a blaSME positive S. marcescens isolate) was incorrectly positive for blaOXA-48 by CARBA 5. No cross reactivity was observed. The sensitivity and specificity were 100.0% and 98.0%, respectively. CONCLUSIONS: The CARBA 5 assay is highly sensitive and specific and is recommended as a tool for the detection of the main carbapenemases of interest in clinical microbiology laboratories.

Clostridium difficile-associated disease and Helicobacter pylori seroprevalence: A case-control study.

BACKGROUND: Helicobacter pylori inhabits the stomach and causes persistent inflammation, with changes in gastric acidity. However, it is unclear whether the presence of H pylori plays a role in Clostridium difficile-associated disease (CDAD). The study's aim was to examine relationships of H pylori seroprevalence and serum pepsinogens (PGs), as markers of gastric inflammation, with CDAD. MATERIALS AND METHODS: A case-control study was conducted among 49 CDAD cases and 54 controls (median age 82 years). Using enzyme-linked immunosorbent assays, sera were tested for H pylori IgG antibody, and PGI and PGII levels. Helicobacter pylori-positive samples were tested for IgG antibody to recombinant cytotoxin-associated gene A (CagA) virulent protein. Logistic regression models were fitted. RESULTS: Cases and controls were comparable in age (P = .5) and sex distribution (females 62% vs 57%, P = .6). Helicobacter pylori IgG seroprevalence was 47%, of whom 23% were CagA seropositives. Among cases compared to controls, 43% vs 28% were H pylori seropositive but lacking CagA IgG antibody: adjusted odd ratio (OR) 3.43 (95% confidence intervals [CI] 1.29-9.10); 18% vs 4% were positive for CagA phenotype: adjusted OR 9.32 (95% CI 1.61-53.76). This association was not affected by PG levels. CONCLUSIONS: Helicobacter pylori infection, especially with CagA virulent phenotype, might predispose to C difficile infection in elderly patients.

The potential benefit of a second C-reactive protein measurement in patients with gram-negative bacteraemia presenting to the emergency medicine department.

BACKGROUND: Low C-reactive protein in acute bacterial infections could convey the erroneous impression of a mild infection. We focussed on gram-negative bacteraemia, a phenomenon frequently seen at the emergency room. METHODS: Of 2200 patients with gram-negative bacteraemia, 460 patients with first C-reactive protein <30 mg/L and 460 patients with C-reactive protein >187 mg/L were reviewed. Following exclusions, we finally investigated 229 and 289 patients with low and high C-reactive protein concentrations, respectively. RESULTS: The cohort was divided into low and high C-reactive protein groups. Median first C-reactive protein was 13.6 and 219.9 mg/L, respectively (interquartile range 6.4-21.6 and 195-270.1). Compared to patients with first high C-reactive protein, patients with first low C-reactive protein concentrations had a significant five-fold higher C-reactive protein level with their second test. CONCLUSIONS: Patients with gram-negative bacteraemia can present with C-reactive protein within the range of apparently healthy individuals. A second C-reactive protein might help to avoid an erroneous decision regarding the severity of the infection.

The implementation of rapid microbial identification via MALDI-ToF reduces mortality in gram-negative but not gram-positive bacteremia.

Our goals were to study the effect of rapid microbial identification (RMI) of positive blood culture on patient's outcome and to identify specific microbiological characteristics related to clinical benefit of RMI. This was a retrospective-cohort study of hospitalized, adult patients with bacteremia. The outcome of patients with bacteremia episodes was compared before vs. after the initiation of RMI. RMI was done by matrix-assisted laser desorption/ionization time-of-flight testing of microcolonies. The study included 1460 and 2710 cases in the pre- and post-intervention periods, respectively. There were similar rates of gram-negative, gram-positive, anaerobes, and polymicrobial infections, but higher rate of contaminants in the intervention period (39.9 vs. 43.7%, p = 0.019). The median time-to-identification decreased from 47.5 to 21.3 h (p < 0.001). Post-intervention, the median LOS declined from 10.83 to 9.79 days (p = 0.016), the rate of ICU transfer declined from 13.8 to 11.6% (p = 0.054), and the mortality rate declined from 20.9 to 18.3% (p = 0.047). The improvement in outcome variables remained statistically significant in multivariate analysis when performed for all episodes and non-contaminants but not for contaminants. The mortality declined in gram-negative bacteremia (20% vs. 15.5%, p = 0.005 in multivariate analysis) but not in gram-positive bacteremia (18.1% vs. 18.5%). RMI reduces mortality from gram-negative but not gram-positive bacteremia.

Clinical benefits of FilmArray meningitis-encephalitis PCR assay in partially-treated bacterial meningitis in Israel.

BACKGROUND: Management of partially-treated, community-acquired bacterial meningitis (PCBM) is commonly compromised by lack of microbiological diagnosis. We aimed to analyze the impact of FilmArray Meningitis-Encephalitis (FA-ME) PCR on the management of PCBM. METHODS: Comparison of treatment variables of PCBM cases between two periods, before (6.5 years, control group) and after (2 years, study group) the application of FA-ME PCR assay. RESULTS: The total duration of antimicrobial treatment in the study group (n = 8) was significantly shorter than the control group (n = 23) (9.5 ± 3.7 days vs. 15.2 ± 5 days, p = 0.007). The percentage of narrow-spectrum regimens was significantly higher in the study group (78 ± 11% vs. 40 ± 9%, p = 0.03). There was a significant difference in implementation of antimicrobial chemoprophylaxis for close contacts (4/8 (50%) vs. 1/23 (4%), p = 0.01). CONCLUSIONS: The use of FA-ME PCR provides significant benefits in the management of PCBM by shortening duration of antibiotic treatment, increasing the use of narrow-spectrum regimens, and allowing proper administration of antimicrobial chemoprophylaxis. TRIAL REGISTRATION: The study was approved and retrospectively registered by the Tel-Aviv Sourasky Medical Center ( 0378-17-TLV , 10/17/2017) and Rabin Medical Center ( 0270-18-RMC , 11/11/2018) Ethics committees and conforms to recognized standards.

Retrospective study showed that bacterial gastroenteritis was an important cause of bloody stools in newborn infants.

AIM: Acute bacterial gastroenteritis is a major cause of morbidity and mortality, especially in the developing countries. We examined the incidence, clinical features and outcomes in the first week of life. METHODS: This was a retrospective study of culture-proven bacterial gastroenteritis in newborn infants that were diagnosed between January 2011 and September 2018 in a tertiary centre in Israel. RESULTS: There were 10 cases of culture-proven bacterial gastroenteritis, detected out of 91 stool cultures. All infants were born vaginally and nine were full-term infants. The annual incidence was 0.096 per 1000 live births. The responsible pathogen was Campylobacter in six patients, Salmonella in two and Shigella sonnei in two. The mean age of disease onset was two days of life. Antibiotics were given to five patients, but were inappropriate in two cases. Only one patient with the Shigella sonnei infection required respiratory support. All patients fully recovered. CONCLUSION: One in ten newborn infants with bloody stools had bacterial gastroenteritis, contradicting the low rates found in other studies and indicating the importance of considering this diagnosis. Antimicrobials active against Salmonella or Shigella should be given to newborn infants who have bloody stools and look ill.

Paediatric community-acquired bacteraemia, pneumococcal invasive disease and antibiotic resistance fell after the pneumococcal conjugate vaccine was introduced.

AIM: This study examined the impact of the routine pneumococcal conjugate vaccination (PCV) on childhood community-acquired bacteraemia (CAB) and antibiotic resistance patterns in Israeli children. METHODS: Israel added the PCV vaccine to its national immunisation programme in July 2009. We retrospectively analysed the medical records of all patients with CAB under 18 years at three children's hospitals in Tel Aviv and Jerusalem from 2007 to 2015. The microbiological data, clinical presentation, pneumococcal serotype distribution, antibiotic susceptibility and outcomes of infections were compared before and after the vaccine was introduced. RESULTS: There were 511 904 emergency department visits and 125 922 children were hospitalised. Of those, 238 had CAB before vaccination was introduced (mean age 17 months) and 316 had CAB after the introduction (mean age 21 months). Emergency department presentations for CAB fell from 141.8 to 91.8 per 100 000 visits: a relative risk reduction (RRR) of 35%. Hospitalisations for CAB decreased from 430 to 337 per 100 000 admissions: an RRR of 22%. Hospitalisations due to Staphylococcus aureus increased significantly and penicillin nonsusceptible blood Streptococcus pneumoniae isolates decreased significantly. CONCLUSION: Introducing national pneumococcal conjugate vaccination significantly changed the epidemiology of CAB, with reduced antibiotic-resistant Streptococcus pneumoniae and increased hospitalisation rates for Staphylococcus aureus infections.

Risk factors for recurrent Clostridium difficile infection in a tertiary hospital in Israel.

To estimate the rate and identified risk factors for recurrent Clostridium difficile infection (rCDI) in Israel. We conducted a retro-prospective case-control study of all adult (age ≥ 18 years) patients with an initial episode of CDI (iCDI) at Tel Aviv Sourasky Medical Center from January 1, 2012 to December 31, 2014. We collected demographic, clinical, and epidemiological information for patients who were classified as recurrent (cases) and non-recurrent (control) groups. In total, 648 patients with iCDI were identified in the study. During the 36-month study period, 82 (12.7%) patients had at least one rCDI identified. We identified several factors as independent variables significantly associated with recurrent CDI: functional disability, severity of the initial infection, continuous non-Clostridium difficile antibiotic treatment with third-generation cephalosporins or clindamycin, and iCDI treatment with metronidazole and vancomycin; however, neutropenia had high measure of effect as a predictor for rCDI (adjusted odds ratio, 7.9; 95% confidence interval, 1.27-49.58; p = 0.026). The identification of the main modifiable risk factors for recurrent CDI, continuous non-Clostridium difficile antibiotics after diagnosis of the initial infection, and antibiotic treatment with third-generation cephalosporins or clindamycin are critical in reducing the spread of recurrent infection with Clostridium difficile in hospital.

Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel.

Candida auris and C. haemulonii are closely related, multidrug-resistant emerging fungal pathogens that are not readily distinguishable with phenotypic assays. We studied C. auris and C. haemulonii clinical isolates from 2 hospitals in central Israel. C. auris was isolated in 5 patients with nosocomial bloodstream infection, and C. haemulonii was found as a colonizer of leg wounds at a peripheral vascular disease clinic. Liberal use of topical miconazole and close contact among patients were implicated in C. haemulonii transmission. C. auris exhibited higher thermotolerance, virulence in a mouse infection model, and ATP-dependent drug efflux activity than C. haemulonii. Comparison of ribosomal DNA sequences found that C. auris strains from Israel were phylogenetically distinct from isolates from East Asia, South Africa and Kuwait, whereas C. haemulonii strains from different countries were closely interrelated. Our findings highlight the pathogenicity of C. auris and underscore the need to limit its spread.