The impact of Boric Acid tubes on quantitative urinary bacterial cultures in hospitalized patients.

INTRODUCTION: The accuracy of urine culture results can be affected by pre-analytical factors such as transport delays and storage conditions. The objectives of this study were to analyze urine collection practices and assess the impact of introducing boric acid tubes for urine collection on quantitative urinary bacterial cultures of hospitalized patients in medical wards. METHODS: A quasi-experimental pre-post study conducted in an acute care facility. In the pre-intervention phase (2020-2021), urine samples were transported without preservatives at room temperature. In 2022 (post-intervention), we transitioned to boric acid transport tubes, evaluating its effect on significant bacterial growth (≥ 105 CFU/ml). Bivariate and multivariate analyses identified predictors of culture positivity. RESULTS: Throughout the duration of the study, a total of 12,660 urine cultures were analyzed. Date and time documentation was complete for 38.3% of specimens. Culture positivity was higher with longer processing times: positivity was 21.3% (220/1034) when specimens were processed within 4 h, 28.4% (955/3364) when processed in 4-24 h, and 32.9% (137/417) when processed after 24 h (p < 0.0001). For 4-24-hour processing, positivity decreased from 30.4% (704/2317) pre-intervention to 24.0% (251/1047) post-intervention (p < 0.001), with no significant changes in < 4 or ≥ 24-hour specimens. Stratified analysis by processing time revealed that the intervention was associated with reduced positivity only in cultures processed within 4-24 h (OR 0.80, 95% CI 0.67-0.94; p = 0.008). CONCLUSION: The introduction of boric acid transport tubes predominantly influenced cultures transported within a 4-24-hour window. This presents an opportunity to improve urine tract infection diagnostic practices in healthcare settings.

Nationwide Outbreak of Candida auris Infections Driven by COVID-19 Hospitalizations, Israel, 2021-2022

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

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.

Short- and long-term mortality in patients with urosepsis caused by Escherichia coli susceptible and resistant to 3rd generation cephalosporins.

BACKGROUND: The aim of this study was to compare short- and long-term mortality among patients with urosepsis caused by Escherichia coli susceptibile (EC-SC) and resistant (EC-RC) to 3rd generation cephalosporins. METHODS: A retrospective cohort study that included all patients with E. coli urosepsis admitted to a 700-bed hospital from January 2014 until December 2019. Mortality up to 30 days, 6 months and 1 year was assessed using logistic multivariate regression analysis and Cox regression analysis. RESULTS: A total of 313 adult were included, 195 with EC-SC and 118 patients with EC-RC. 205 were females (74%), mean age was 79 (SD 12) years. Mean Charlson score was 4.93 (SD 2.18) in the EC-SC group and 5.74 (SD 1.92) in the EC-RC group. Appropriate empiric antibiotic therapy was initiated in 245 (78.3%) patients, 100% in the EC-SC group but only 42.5% in the EC-RC group. 30-day mortality occurred in 12 (6.3%) of EC-SC group and 15 (12.7%) in the EC-RC group. Factors independently associated with 30-day mortality were Charlson score, Pitt bacteremia score, fever upon admission and infection with a EC-RC. Appropriate antibiotic therapy was not independently associated with 30-day mortality. Differences in mortality between groups remained significant one year after the infection and were significantly associated with the Charlson co-morbidity score. CONCLUSIONS: Mortality in patients with urosepsis due to E. coli is highly affected by age and comorbidities. Although mortality was higher in the EC-RC group, we could not demonstrate an association with inappropriate empirical antibiotic treatment. Mortality remained higher at 6 months and 1 year long after the infection resolved but was associated mainly with co-morbidity.

Aminoglycoside versus carbapenem or piperacillin/tazobactam treatment for bloodstream infections of urinary source caused by Gram-negative ESBL-producing Enterobacteriaceae.

OBJECTIVES: We studied the performance of aminoglycosides in treating bloodstream infections (BSIs) of urinary source caused by ESBL-producing Enterobacteriaceae (ESBL-EB). METHODS: In a retrospective study of 193 patients with a clinical diagnosis of urinary tract infection, pyelonephritis or urosepsis and blood and urine cultures positive for ESBL-EB, patients were grouped according to whether they were treated with an aminoglycoside, a carbapenem or piperacillin/tazobactam. Multivariate analysis was used to define risk factors for mortality with inverse probability of treatment weighting used to minimize confounding. The primary efficacy outcome was 30 day mortality. The primary safety outcome was acute kidney injury (AKI) at 14 days. RESULTS: Mean age was 79.3 years. Dementia, chronic kidney disease and the presence of a urinary catheter were common. Thirty-two (16.6%) patients died and risk factors for mortality included age, high Charlson score, presentation with severe sepsis/septic shock and infection with bacteria other than Escherichia coli. Aminoglycosides were non-inferior compared with other antibiotics regarding 30 day mortality [13.0% versus 21.2%, respectively; adjusted risk difference=10.29% (-0.82% to 21.41%)], but did not reach non-inferiority for bacteriuria recurrence [48.9% versus 44.7%, respectively; adjusted risk difference=-8.72% (-30.87% to 13.43%)]. AKI developed at a similar rate in both treatment groups: 12.0% versus 10.6%, respectively [OR=1.14 (0.46-2.81)]. Aminoglycosides were more efficacious in E. coli infections compared with other ESBL-EB. CONCLUSIONS: We demonstrated the efficacy and safety of aminoglycosides in treating BSI of urinary source caused by ESBL-EB. This carbapenem-sparing approach can assist in avoiding excessive carbapenem use without compromising outcomes.

Outdated allergens are similar to unexpired extracts for the detection of allergen sensitization.

Background: Allergen extracts have relatively short shelf lives, which limits their use and increase financial loss and waste on unused extracts. It is thus important to determine if efficacy persists beyond the expiration date. Objective: To determine the in vivo efficacy and bioavailability of outdated allergen extracts for diagnosis of allergic sensitizations. Methods: We enrolled 34 participants with allergic rhinitis and 5 participants with Hymenoptera hypersensitivity. After confirming allergen sensitization with the unexpired extracts, each participant had a second skin test with the matched outdated one (up to 7 years after the expiration date). All pairs of extracts were from the same company, stored under identical conditions, and tested for microbiologic contamination. The results of 356 skin-prick tests between expired and 111 unexpired extracts were compared. Results: None of the extracts had bacterial or fungal contamination. All outdated extracts produced a positive wheal reaction, with an average of 9.4 mm, which was not significantly different than the unexpired allergens. Seven years outdated lyophilized Hymenoptera extracts showed no significant differences in the wheal's size for the intradermal test at 1 µg/mL, between 5 and 9 mm. Conclusion: Outdated allergen extracts were safe and did not seem to differ in potency and bioavailability from unexpired extracts for the detection of allergen sensitization by skin-prick testing. These results supported our hypothesis that allergen extracts have efficacy and bioavailability that extend beyond the expiry date provided by the manufacturer. For the diagnosis of aeroallergens and Hymenoptera sensitization, it seemed that allergens can be used beyond the expiration date.

Escherichia coli isolates from patients with bacteremic urinary tract infection are genetically distinct from those derived from sepsis following prostate transrectal biopsy.

BACKGROUND: Transrectal ultrasound-guided (TRUS) prostate biopsy is a very common procedure that is generally considered relatively safe. However, severe sepsis can occur after TRUS prostate biopsies, with Escherichia coli being the predominant causative agent. A common perception is that the bacteria that cause post-TRUS prostate biopsy infections originate in the urinary tract, but this view has not been adequately tested. Yet other authors believe on the basis of indirect evidence that the pathogens are introduced into the bloodstream by the biopsy needle after passage through the rectal mucosa. METHODS: We compared E. coli isolates from male patients with bacteremic urinary tract infection (B-UTI) to isolates of patients with post prostate biopsy sepsis (PPBS), in terms of their sequence types, determined by multi-locus sequence typing (MLST) and their virulence markers. RESULTS: B-UTI isolates were much richer in virulence genes than were PPBS isolates, supporting the hypothesis that E. coli causing PPBS derive directly from the rectum. Sequence type 131 (ST131) strains and related strain from the ST131 were common (>30%) among the E. coli isolates from PPBS patients as well as from B-UTI patients and all these strains expressed extended spectrum beta-lactamases. CONCLUSIONS: Our finding supports the hypothesis that E. coli causing PPBS derive directly from the rectum, bypassing the urinary tract, and therefore do not require many of the virulence capabilities necessary for an E. coli strain that must persist in the urinary tract. In light of the increasing prevalence of highly resistant E. coli strains, a new approach for prevention of PPBS is urgently required.

The Value of Rectal Cultures in Treatment of Sepsis Following Post-Transrectal Ultrasound-Guided Prostate Biopsy.

BACKGROUND: Cases with sepsis after transrectal ultrasound-guided prostate biopsy (TRUSPB) were documented, with special focus on cultures and susceptibility of isolates. We also evaluated the contribution of concomitant rectal cultures to the treatment of selective cases. MATERIALS AND METHODS: Patients with sepsis after TRUSPB were followed prospectively. Manifestations and risk factors for antimicrobial resistance were documented. Results of urine and blood cultures and antimicrobial susceptibility were recorded for all participating patients. In 40 patients, rectal swab cultures were obtained concomitantly. RESULTS: Ninety-five patients were consecutively studied. Sepsis symptoms started showing up within 48 h after biopsy in 93% of patients. At least one of the cultures was positive in 72 patients. E. coli grew in 70 cases; isolates were highly resistant: 67% displayed multidrug-resistance. Rectal cultures grew E. coli in 38 cases. In patients with positive E. coli in rectum and in at least one additional culture (blood and/or urine), the antibiogram was identical in all cases but one. Eight cases had negative cultures. CONCLUSION: The prevalence of antimicrobial resistance among E. coli isolates from patients with TRUSPB sepsis was alarming. Susceptibilities of rectal E. coli isolates used for deescalation of initial empiric treatment in culture-negative TRUSPB sepsis can contribute to the reduction of broad-spectrum antibiotics exposure.

Contribution of active surveillance cultures to the control of hospital-acquired carbapenem-resistant Acinetobacter baumannii in an endemic hospital setting.

BACKGROUND: Despite the increasing rates of carbapenem-resistant Acinetobacter baumannii (CRAB) carriage among hospitalized patients in endemic settings, the role of active surveillance cultures and cohorting is still debated. We sought to determine the long-term effect of a multifaceted infection-control intervention on the incidence of CRAB in an endemic setting. METHODS: A prospective, quasi-experimental study was performed at a 670-bed, acute-care hospital. The study consisted of 4 phases. In phase I, basic infection control measures were used. In phase II, CRAB carriers were cohorted in a single ward with dedicated nursing and enhanced environmental cleaning. In phase III large-scale screening in high-risk units was implemented. Phase IV comprised a 15-month follow-up period. RESULTS: During the baseline period, the mean incidence rate (IDR) of CRAB was 44 per 100,000 patient days (95% CI, 37.7-54.1). No significant decrease was observed during phase II (IDR, 40.8 per 100,000 patient days; 95% CI, 30.0-56.7; P = .97). During phase III, despite high compliance with control measures, ongoing transmission in several wards was observed and the mean IDR was 53.9 per 100,000 patient days (95% CI, 40.5-72.2; P = .55). In phase IV, following the implementation of large-scale screening, a significant decrease in the mean IDR was observed (25.8 per 100,000 patient days; 95% CI, 19.9-33.5; P = .03). An overall reduction of CRAB rate was observed between phase I and phase IV (rate ratio, 0.6; 95% CI, 0.4-0.9; P < .001). CONCLUSIONS: The comprehensive intervention that included intensified control measures with routine active screening cultures was effective in reducing the incidence of CRAB in an endemic hospital setting.

Genome sequence of two novel virulent clinical strains of Burkholderia pseudomallei isolated from acute melioidosis cases imported to Israel from India and Thailand.

OBJECTIVE: Burkholderia pseudomallei, the etiological cause of melioidosis, is a soil saprophyte endemic in South-East Asia, where it constitutes a public health concern of high-priority. Melioidosis cases are sporadically identified in nonendemic areas, usually associated with travelers or import of goods from endemic regions. Due to extensive intercontinental traveling and the anticipated climate change-associated alterations of the soil bacterial flora, there is an increasing concern for inadvertent establishment of novel endemic areas, which may expand the global burden of melioidosis. Rapid diagnosis, isolation and characterization of B. pseudomallei isolates is therefore of utmost importance particularly in non-endemic locations. DATA DESCRIPTION: We report the genome sequences of two novel clinical isolates (MWH2021 and MST2022) of B. pseudomallei identified in distinct acute cases of melioidosis diagnosed in two individuals arriving to Israel from India and Thailand, respectively. The data includes preliminary genetic analysis of the genomes determining their phylogenetic classification in rapport to the genomes of 131 B. pseudomallei strains documented in the NCBI database. Inspection of the genomic data revealed the presence or absence of loci encoding for several documented virulence determinants involved in the molecular pathogenesis of melioidosis. Virulence analysis in murine models of acute or chronic melioidosis established that both strains belong to the highly virulent class of B. pseudomalleii.

Penile herpes simplex virus type 1 infection presenting two and a half years after Jewish ritual circumcision of an infant.

The association between Jewish ritual circumcision and genital herpes simplex virus type 1 infection has been well described. We report a case of genital herpes that first presented at the age of 2½ years. We believe that the infection was acquired asymptomatically through direct orogenital suction performed during circumcision in the newborn period.

Characterization of community-acquired Clostridioides difficile strains in Israel, 2020-2022.

Background: The prevalence of community-acquired Clostridioides difficile infection (CA-CDI) has been rising, due to changes in antibiotics prescribing practices, emergence of hypervirulent strains and improved diagnostics. This study explored CA-CDI epidemiology by examining strain diversity and virulence factors of CA-CDI isolates collected across several geographical regions in Israel. Methods: Stool samples of 126 CA-CDI patients were subjected to PCR and an immunoassay to identify toxin genes and proteins, respectively. Toxin loci PaLoc and PaCdt were detected by whole-genome sequencing (WGS). Biofilm production was assessed by crystal violet-based assay. Minimum inhibitory concentration was determined using the Etest technique or agar dilution. WGS and multi-locus sequence typing (MLST) were used to classify strains and investigate genetic diversity. Results: Sequence types (ST) 2 (17, 13.5%), ST42 (13, 10.3%), ST104 (10, 8%) and ST11 (9, 7.1%) were the most common. All (117, 92.8%) but ST11 belonged to Clade 1. No associations were found between ST and gender, geographic area or antibiotic susceptibility. Although all strains harbored toxins genes, 34 (27%) produced toxin A only, and 54 (42.9%) strains produced toxin B only; 38 (30.2%) produced both toxins. Most isolates were biofilm-producers (118, 93.6%), primarily weak producers (83/118, 70.3%). ST was significantly associated with both biofilm and toxin production. Conclusion: C. difficile isolates in Israel community exhibit high ST diversity, with no dominant strain. Other factors may influence the clinical outcomes of CDI such as toxin production, antibiotic resistance and biofilm production. Further studies are needed to better understand the dynamics and influence of these factors on CA-CDI.

Response Rate of the Third and Fourth Doses of the BNT162b2 Vaccine Administered to Cancer Patients Undergoing Active Anti-Neoplastic Treatments.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response rate of administering the third and fourth vaccine doses to cancer patients receiving active anti-neoplastic treatment. A total of 142 patients received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients who received three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients who received two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p = 0.02 and 17.15 (95% CI 5.01-58.7), p < 0.01, respectively). Unlike the response after two doses, the third and fourth BNT162b2 vaccine booster doses had an increased efficacy of 95-100% in cancer patients while undergoing active treatment. This result could be explained by different mechanisms including the development of memory B cells.

A Multi-Laboratory Evaluation of Commercial Monkeypox Virus Molecular Tests.

In this report, we describe the first national scale multi-laboratory evaluation of monkeypox virus (MPXV) DNA commercial PCR kits. The objective of this study was to evaluate 2 kits by different diagnostic laboratories across Israel. Ten standardized samples were tested simultaneously using the Novaplex (15 laboratories) and Bio-Speedy (seven laboratories) kits. An in-house assay based on previously published reactions was used as reference. Comparison of the results showed high intra-assay agreement between laboratories, with small variations for most samples. The in-house assay had an analytical detection limit of less than 10 copies per reaction. While the 2 commercial kits were able to detect specimens with low viral loads similarly to the in-house assay, significant differences were observed, in the Cq values and relative fluorescence (RF), between the assays. The RF signal of the in-house and Bio-Speedy assays ranged between 5,000 and 10,000 RFU, while the signal in the Novaplex assay was less than 600 RFU. Due to the kit measurement protocol, the Cq values of the Bio-Speedy kit were 5 to 7.5 cycles lower than those of the in-house assay. On the contrary, the Cq values of the Novaplex kit were significantly higher than those of the in-house assay, with differences of 3 to 5 cycles per sample. Our results suggest that while all assays were similar in their overall sensitivity, direct comparison of Cq values between them may be misleading. To our knowledge, this is the first methodical evaluation of commercial MPX test kits. We therefore anticipate that this study would help diagnostic laboratories in choosing a specific MPX detection assay. IMPORTANCE To the best of our knowledge, this study is the first methodical evaluation of commercial kits designed for Monkeypox virus detection. This was done by performing the same tests using the same sample set in multiple laboratories, simultaneously, on a national scale. It therefore provides important and unique information on the performance of such kits and provides a guideline for choosing the assay of choice for monkeypox virus diagnosis in a standard diagnostic laboratory. It also demonstrates potential complications when trying to compare the results of different assays, even when testing exactly the same samples, under identical conditions.

Sexually transmitted Escherichia coli urethritis and orchiepididymitis.

We describe herein a case of uropathogenic Escherichia coli urethritis and orchiepididymitis in a heterosexual man, which he had acquired sexually from his girlfriend. The identity of the genital isolates from both partners was confirmed by pulsed-field gel electrophoresis.

Evaluation of SARS-CoV-2 in the Vaginal Secretions of Women with COVID-19: A Prospective Study.

OBJECTIVE: We aimed to investigate the likelihood of vaginal colonization with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pregnant and non-pregnant women with Coronavrus Disease 2019 (COVID-19). MATERIALS AND METHODS: Vaginal swabs were taken from women diagnosed with mild to moderately acute SARS-CoV-2 infection, at Wolfson Medical Center, Israel, from March 2020 through October 2020. COVID-19 was diagnosed by real-time polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs. Vaginal swabs were tested for the presence of SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In total, 51 women diagnosed with COVID-19 were included in the study. Of the 51 women with COVID-19 enrolled in this study, 16 (31.4%) were pregnant at enrollment and 35 (68.6%) were non-pregnant. Mean age was 43.5 ± 15.3 years (range 21-74 years). Compared to the non-pregnant group, the pregnant group was characterized by a higher white blood cell and absolute neutrophil count (p = 0.02 and p = 0.027, respectively). The non-pregnant patients were more likely to have chronic diseases (p = 0.035) and to be hospitalized (p < 0.001). Only one patient (1.9%) aged 60 years tested positive for SARS-CoV-2 in vaginal secretions. Mean gestational age at the diagnosis of COVID-19 of the pregnant group was 32.3 ± 7.8 weeks. Thirteen patients delivered during the study period; all delivered at term without obstetric complications and all neonates were healthy. CONCLUSIONS: Detection of SARS-CoV-2 in the vaginal secretions of patients diagnosed with COVID-19 is rare. Vaginal colonization may occur during the viremia phase of the disease, although infectivity from vaginal colonization needs to be proven.

Efficacy of the mRNA-Based BNT162b2 COVID-19 Vaccine in Patients with Solid Malignancies Treated with Anti-Neoplastic Drugs.

The BNT162b2 vaccine was shown to be highly effective in reducing the risk of COVID-19 infection in healthy individuals and patients with chronic disease. However, there are little data regarding its efficacy in patients treated for cancer. We analyzed the humoral response following vaccination with the second dose of BNT162b2 in 140 patients with solid malignancies who were receiving anti-cancer therapy at the time of vaccination and 215 participants who had not been diagnosed with cancer. Multivariate analysis was performed, followed by matching the two groups by age, gender and days from vaccination. The humoral response in the cancer patient group was significantly lower than in the non-cancer group: 20/140 seronegative (14.3%) vs. 3/215 (1.4%), p < 0.001; median IgG levels 2231 AU/mL (IQR 445-8023) vs. 4100 (IQR 2231-6774) p = 0.001 respectively. The odds ratio for negative serology results in cancer patients adjusted by age and gender was 7.35 compared to participants without cancer. This effect was observed only in chemotherapy treated patients: 17/73 seronegative (23.3%) vs. 3/215 (1.4%), p < 0.001; median IgG 1361 AU/mL vs. 4100, p < 0.001 but not in patients treated with non-chemotherapeutic drugs. Reduced immunogenicity to COVID-19 vaccine among chemotherapy-treated cancer patients, raises the need to continue exercising protective measures after vaccination in these patients.

National multicenter study of predictors and outcomes of bacteremia upon hospital admission caused by Enterobacteriaceae producing extended-spectrum beta-lactamases.

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.

Impact of Pneumococcal Conjugate Vaccines on Selected Head and Neck Infections in Hospitalized Israeli Children.

BACKGROUND: Streptococcus pneumoniae is a major pathogen of pediatric head and neck infections (HNIs), for example, acute otitis media (AOM), acute mastoiditis, acute bacterial sinusitis and meningitis. The aim of this study was to characterize the epidemiology of pneumococcal HNIs (pHNIs) before, during and after the introduction of pneumococcal conjugate vaccines (PCVs). METHODS: Children 0-16 years of age, who were hospitalized with HNIs in the pediatrics department in a general hospital between January 1, 2007, and December 31, 2014, were retrospectively identified. Study years were categorized according to the PCV introduction timeline: 2007-2008: "pre-PCV years"; 2009-2011: "transition years" and 2012-2014: "post-PCV years." pHNIs episodes were defined if pneumococcal culture or urine antigen was positive. Children who received ≥2 doses of PCV7/PCV13 were considered as immunized. All other children were considered as unimmunized. RESULTS: HNIs accounted for 2.5%-4.7% of the total admissions; 3%-17% of them were pHNIs. Eighty-seven pHNI episodes were identified: AOM (n = 42), acute mastoiditis (n = 28) and meningitis (n = 17). There was a downward trend in the overall incidence of HNIs, and particularly of pHNIs, in the post-PCV years. The average age and hospitalization duration of children with HNIs/pHNIs remained stable during the study years. In 2009-2010, pHNIs incidence sharply decreased, from 7 to 1.74/1000 hospitalized children/year, due to ~55% reduction of pneumococcal AOM episodes. An additional decrease was observed in the post-PCV years (1.62/1000 hospitalized children/year). Immunized children were less likely to present with pHNIs (P = 0.001) but were more likely to undergo surgery (P = 0.042). CONCLUSION: We observed a reduction in pHNIs incidence after PCV program implementation.