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Biofilm formation and toxin production are some of the virulence factors of Clostridioides difficile (C. difficile), which causes hospital-acquired C. difficile infection (HA-CDI). This work investigated the prevalence and distribution of different strains recovered from HA-CDI patients hospitalized in 4 medical centres across Israel, and characterized strains' virulence factors and antibiotic susceptibility. One-hundred and eighty-eight faecal samples were collected. C. difficile 's toxins were detected by the CerTest Clostridium difficile GDH + Toxin A + B combo card test kit. Toxin loci PaLoc and PaCdt were detected by whole-genome sequencing (WGS). Multi-locus sequence typing (MLST) was performed to classify strains. Biofilm production was assessed by crystal violet. Antibiotic susceptibility was determined using Etest. Fidaxomicin susceptibility was tested via agar dilution. Sequence type (ST) 42 was the most (13.8%) common strain. All strains harboured the 2 toxins genes; 6.9% had the binary toxin. Most isolates were susceptible to metronidazole (98.9%) and vancomycin (99.5%). Eleven (5.85%) isolates were fidaxomicin-resistant. Biofilm production capacity was associated with ST (p < 0.001). In conclusion, a broad variety of C. difficile strains circulate in Israel's medical centres. Further studies are needed to explore the differences and their contribution to HA-CDI epidemiology.
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Antibacterianos , Biofilmes , Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Testes de Sensibilidade Microbiana , Fatores de Virulência , Clostridioides difficile/genética , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/patogenicidade , Humanos , Israel/epidemiologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/epidemiologia , Antibacterianos/farmacologia , Fatores de Virulência/genética , Masculino , Feminino , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Idoso , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Adulto , Idoso de 80 Anos ou mais , Sequenciamento Completo do Genoma , Fezes/microbiologiaRESUMO
Background/Objectives:Mycoplasma genitalium (MG) infections and antibiotic resistance are increasing in prevalence while treatment options are limited. Limited data exist regarding MG resistance in Israel. Our aim was to study the prevalence of MG resistance in a sexually transmitted infection (STI) clinic in Israel. Methods: We performed a single-center retrospective study among patients attending an STI clinic during 2019-2020. MG isolates were tested to detect their resistance to azithromycin and fluoroquinolones (FQs) using commercial kits (Allplex™ MG & AziR Assay, Allplex™ MG & MoxiR Assay). We collected patient data regarding the risk factors for STIs and resistance. A multivariate logistic regression model was used to identify the risk factors for resistance. Results: Of the 142 patients who tested positive for MG, 50 (35.2%) and 22 (15.5%) had resistant mutations to azithromycin and FQ, respectively, and 13 (9.2%) showed resistance to both agents. In a multivariate logistic regression model, men who have sex with men (RR 7.01 95% CI 3.00-16.33) and past STIs (RR 2.33 95% CI 1.01-5.34) were independent risk factors for azithromycin resistance. Conclusions: We found a high prevalence of azithromycin resistance and, to a lesser degree, FQ resistance. These findings may help design the treatment guidelines and support routine resistance testing in high-risk populations.
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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.
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Bactérias , Ácidos Bóricos , Infecções Urinárias , Humanos , Ácidos Bóricos/farmacologia , Bactérias/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Infecções Urinárias/microbiologia , Infecções Urinárias/diagnóstico , Manejo de Espécimes/métodos , Hospitalização , Masculino , Fatores de Tempo , Feminino , Coleta de Urina/métodos , Urina/microbiologia , Urinálise/métodosRESUMO
The COVID-19 pandemic, resulting from the emergence of the novel coronavirus SARS-CoV-2, posed unprecedented challenges to global health systems as no proven therapy was available. Initially, COVID-19 convalescent plasma (CCP) from recovered COVID-19 patients showed promise as a therapeutic option. However, the efficacy of this approach was closely correlated with the neutralizing antibody titer in the administered plasma and thus effectiveness was not always guaranteed. In response, hyperimmune immunoglobulins (hIG) derived from CCP obtained by apheresis from recovered or vaccinated individuals emerged as a potential alternative. hIG were purified through stringent chromatographic processing from CCP units and displayed varying results in clinical trials, although it seems likely that they improved outcomes compared to placebo or CCP at day 28, particularly in unvaccinated patients. The variability in the effect of hIG likely stems from factors such as the timing of outcome assessment, the administered dose of hIG, the patients' immunological background, and the matching between the variant infecting patients and the neutralization ability of the immunoglobulin batch, which depended on the timing of the CCP collection. Despite logistical challenges and high production costs, hIG showcase advantages over CCP, offering versatility in administration routes and eliminating the need for blood matching, thus facilitating administration in the community, and allowing for variant-specific preparations. hIG appear to be of particular importance in the treatment of immunocompromised patients and patients with persistent COVID-19, although studies in these populations are lacking. Non-human alternatives, such as equine-derived hIG and recombinant hIG, may provide a solution to the logistical challenges of large-scale hIG preparation. Further study is needed to explore these avenues. Establishing the infrastructure for large-scale hIG production independent of plasma donations emerges as a strategic approach for future pandemics, justifying exploration and promotion by health authorities.
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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.
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Burkholderia pseudomallei , Genoma Bacteriano , Melioidose , Filogenia , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/isolamento & purificação , Burkholderia pseudomallei/patogenicidade , Melioidose/microbiologia , Melioidose/epidemiologia , Tailândia/epidemiologia , Humanos , Genoma Bacteriano/genética , Índia , Animais , Israel/epidemiologia , Virulência/genética , Camundongos , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Immunocompromised patients with impaired humoral immunity are at risk for persistent COVID-19 (pCOVID), a protracted symptomatic disease with active viral replication. OBJECTIVES: To establish a national consensus statement on the diagnosis, treatment, management, isolation, and prevention of pCOVID in adults. SOURCES: We base our suggestions on the available literature, our own experience, and clinical reasoning. CONTENT: Literature on the treatment of pCOVID is scarce and consists of few case reports and case series. The available studies provide low-quality evidence for monoclonal antibodies, convalescent plasma, antiviral drugs, and immunomodulators. Different combination therapies are described. Continuous viral replication and antiviral treatment may lead to the development of mutations that confer resistance to therapy. IMPLICATIONS: To reduce the risk of resistance and improve outcomes, we suggest treating pCOVID with a combination of antibody-based therapy and two antiviral drugs for duration of 5-10 days. Immunomodulatory therapy can be added in patients with an inflammatory clinical picture. In cases of treatment failure or relapse, prolonged antiviral treatment can be considered. For the prevention of pCOVID, we suggest active and passive vaccination and early initiation of treatment for acute COVID-19. Additional research on pCOVID treatment is urgently needed.
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Antivirais , COVID-19 , Hospedeiro Imunocomprometido , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/terapia , Antivirais/uso terapêutico , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Consenso , Imunização Passiva/métodos , Soroterapia para COVID-19 , Anticorpos Monoclonais/uso terapêuticoRESUMO
INTRODUCTION: Bloodstream Infections (BSI) are a major cause of death and hospitalization among hemodialysis (HD) patients. The rates of BSI among HD patients vary and are influenced by local patient and pathogen characteristics. Modifications in local infection prevention protocols in light of active surveillance of BSI has been shown to improve clinical outcomes. The aim of this study was to further explore factors associated with BSI in a contemporary cohort of HD patients at a public teaching hospital dialysis center in Israel. METHODS: This was a retrospective cohort study of HD patients with a BSI in the years 2014 to 2018. The primary outcome was the occurrence of BSI. Secondary outcomes were to describe the causative pathogens of BSI, and to assess for risk factors for BSI, and mortality. RESULTS: Included were 251 patients. The mean age was 68.5 ± 13.4 years, 66.9% were male. The mean time from initiation of dialysis was 34.76 ± 40.77 months, interquartile range (IQR) 1-47.5 months and the follow up period of the cohort was 25.17 ± 15.9 months. During the observation period, 44 patients (17.5%) developed 54 BSI events, while 10 of them (3.9% of the whole cohort) developed recurrent BSI events. Gram-negative microorganisms caused 46.3% of all BSI events. 31.4% of these BSI were caused by resistant bacteria. In a multivariate logistic regression analysis, patients receiving dialysis through a central line had a significantly increased risk for BSI adjusted Odds Ratio (aOR) 3.907, p = 0.005, whereas patients' weight was mildly protective (aOR 0.971, p = 0.024). CONCLUSIONS: We noted an increased prevalence of gram-negative pathogens in the etiology of BSI in HD patients. Based on our findings, additional empirical antibiotics addressing gram negative bacteria have been added to our empirical treatment protocol. Our findings highlight the need to follow local epidemiology for implementing appropriate preventative measures and for tailoring appropriate empiric antibiotic therapy.
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Bacteriemia , Sepse , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Estudos Retrospectivos , Bacteriemia/epidemiologia , Bacteriemia/etiologia , Sepse/complicações , Bactérias Gram-Negativas , Antibacterianos/uso terapêutico , Fatores de RiscoRESUMO
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 intensiï¬ed control measures with routine active screening cultures was effective in reducing the incidence of CRAB in an endemic hospital setting.
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Infecções por Acinetobacter , Acinetobacter baumannii , Infecção Hospitalar , Humanos , Acinetobacter baumannii/efeitos dos fármacos , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/prevenção & controle , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/tratamento farmacológico , Hospitais , Unidades de Terapia Intensiva , Estudos Prospectivos , Conduta ExpectanteRESUMO
Background: The COVID-19 pandemic was associated with increased rates of hospital-acquired infections. During the early months of the pandemic, we observed high rates of hospital-acquired bloodstream infections (HA-BSIs) among COVID-19 patients, prompting the implementation of intensified prevention measures. Objectives: To assess the prevalence of HA-BSI among mechanically ventilated COVID-19 patients, identify risk factors, and evaluate the effect of prevention measures. Methods: We conducted a retrospective matched case-control study in adult medical step-up units between March 1, 2020, and March 31, 2021. We matched mechanically ventilated COVID-19 patients with ventilated non-COVID-19 patients based on age group and length of stay before ventilation. In response to the high rates of HA-BSI among COVID-19 patients, a comprehensive infection control intervention was implemented. Results: A total of 136 COVID-19 patients were matched with 136 non-COVID-19 patients. No significant differences were observed in pre-hospitalization characteristics. The central venous catheter utilization ratio was higher in COVID-19 patients (83.6%) versus 35.6% in the control group (p < 0.001). During pre-intervention, 35.2% (32/91) of COVID-19 patients developed HA-BSI, compared to 17.8% (13/73) in the control group (p < 0.001). Following the intervention, no significant difference was observed between the groups (17.8% (8/45) versus 15.9% (10 /63), p = 0.79). In a multivariate analysis, HA-BSI was associated with low body mass index (OR 0.9 (95% CI 0.9-1.0), p = 0.015)) and presence of temporary dialysis catheter (OR 2.7 (95% CI 1.0-7.3), p = 0.05)). Conclusions: Mechanically ventilated COVID-19 patients were at higher risk for developing HA-BSI compared to non-COVID-19 patients. Intensified prevention measures were associated with decreased rates of HA-BSI.
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Introduction: GBS may cause a devastating disease in newborns. In early onset disease of the newborn the bacteria are acquired from the colonized mother during delivery. We characterized type VII secretion system (T7SS), exporting small proteins of the WXG100 superfamily, in group B Streptococci (GBS) isolates from pregnant colonized women and newborns with early onset disease (EOD) to better understand T7SS contribution to virulence in these different clinical scenarios. Methods: GBS genomes [N=33, 17 EOD isolates (serotype III/ST17) and 16 colonizing isolates (12 serotype VI/ST1, one serotype VI/ST19, one serotype VI/ST6, and two serotype 3/ST19)] were analyzed for presence of T7SS genes and genes encoding WXG100 proteins. We also perform bioinformatic analysis. Galleria mellonella larvae were used to compare virulence between colonizing, EOD, and mutant EOD isolates. The EOD isolate number 118659 (III/ST17) was used for knocking out the essC gene encoding a membrane-bound ATPase, considered the driver of T7SS. Results: Most GBS T7SS loci encoded core component genes: essC, membrane-embedded proteins (essA; essB), modulators of T7SS activity (esaA; esaB; esaC) and effectors: [esxA (SAG1039); esxB (SAG1030)].Bioinformatic analysis indicated that based on sequence type (ST) the clinicalGBS isolates encode at least three distinct subtypes of T7SS machinery. In all ST1isolates we identified two copies of esxA gene (encoding putative WXG100proteins), when only 23.5% of the ST17 isolates harbored the esxA gene. Five ST17isolates encoded two copies of the essC gene. Orphaned WXG100 molecule(SAG0230), distinct from T7SS locus, were found in all tested strains, except inST17 strains where the locus was found in only 23.5% of the isolates. In ST6 andST19 isolates most of the structure T7SS genes were missing. EOD isolates demonstrated enhanced virulence in G. mellonella modelcompared to colonizing isolates. The 118659DessC strain was attenuated in itskilling ability, and the larvae were more effective in eradicating 118659DessC. Conclusions: We demonstrated that T7SS plays a role during infection. Knocking out the essC gene, considered the driver of T7SS, decreased the virulence of ST17 responsible for EOD, causing them to be less virulent comparable to the virulence observed in colonizing isolates.
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Infecções Estreptocócicas , Sistemas de Secreção Tipo VII , Humanos , Recém-Nascido , Feminino , Gravidez , Gestantes , Sistemas de Secreção Tipo VII/genética , Sistemas de Secreção Tipo VII/metabolismo , Virulência/genética , Streptococcus agalactiae/genética , Sorogrupo , Proteínas de Membrana/genética , Infecções Estreptocócicas/microbiologiaRESUMO
OBJECTIVES: To assess the performance of a test (called BV), integrating the blood levels of three immune proteins into a score, to differentiate bacterial from viral infection among adults with suspected lower respiratory tract infection (LRTI). METHODS: Prospective diagnostic accuracy study, enrolling febrile adults >18 years with LRTI signs or symptoms for less than 7 days presenting to several hospitals' emergency departments in Israel. The main exclusion criterion was immunodeficiency. Reference standard diagnosis (bacterial/viral/indeterminate) was based on three experts independently reviewing comprehensive patient data including follow-up data. BV generated three results: viral infection or other nonbacterial condition (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65) and bacterial infection including co-infection (65 < score ≤ 100). BV performance was assessed against the reference standard with indeterminate reference standard and equivocal BV cases removed. RESULTS: Of 490 enrolled patients, 415 met eligibility criteria (median age 56 years, interquartile range 35). The reference standard classified 104 patients as bacterial, 210 as viral and 101 as indeterminate. BV was equivocal in 9.6% (30/314). Excluding indeterminate reference standard diagnoses and equivocal BV results, BV's sensitivity for bacterial infection was 98.1% (101/103; 95% confidence interval 95.4-100), specificity 88.4% (160/181; 83.7-93.1) and negative predictive value 98.8% (160/162; 97.1-100). DISCUSSION: BV exhibited high diagnostic performance for febrile adults with suspected LRTI among patients with reference standard diagnoses of bacterial or viral LRTI.
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Infecções Bacterianas , Infecções Respiratórias , Viroses , Humanos , Adulto , Pessoa de Meia-Idade , Proteína C-Reativa/análise , Interferon gama , Biomarcadores , Estudos Prospectivos , Ligantes , Sensibilidade e Especificidade , Infecções Bacterianas/diagnóstico , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia , Viroses/diagnóstico , Bactérias , Febre , Fator de Necrose Tumoral alfaRESUMO
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.
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COVID-19 , Candidíase Invasiva , Humanos , Candida/genética , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida auris , Israel/epidemiologia , COVID-19/epidemiologia , Candidíase Invasiva/tratamento farmacológico , Surtos de Doenças , Hospitalização , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: It is unknown whether convalescent immunoglobulins (cIgGs) are better than convalescent plasma (CP) for patients with coronavirus 2019 (COVID-19). METHODS: In this randomized controlled trial, we assigned high risk COVID-19 patients with ≤10 days of symptoms, to receive cIgGs or CP. The primary endpoint was improvement on day 14 according to the World Health Organization scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28, and treatment response in unvaccinated and vaccinated patients. RESULTS: A total of 319 patients were included: 166 received cIgGs and 153 CP. Median age was 64 to 66 years. A total of 112 patients (67.5%) in the cIgG group and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95% confidence interval, -10.1 to 10.4; P = .026), failing to reach noninferiority. More patients receiving cIgG improved by day 28 (136 patients [81.9%] and 108 patients [70.6%], respectively; 95% confidence interval, 1.9-20.7; P < .001; for superiority P = .018). Seventeen patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (P = .136). Sixteen (9.6%) and 23 (15%) patients, respectively, died (P = .172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs 66.1%; P = .024), and survival was better in the cIgG group (89.9% vs 77.4%; P = .066). CONCLUSIONS: cIgGs failed to reach the primary noninferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgGs were better. In the face of new variants, cIgGs are a viable option for treating COVID-19. TRIAL REGISTRATION NUMBER: My Trials MOH_2021-01-14_009667.
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COVID-19 , Humanos , Pessoa de Meia-Idade , Idoso , COVID-19/terapia , SARS-CoV-2 , Imunização Passiva/efeitos adversos , Resultado do Tratamento , Soroterapia para COVID-19 , ImunoglobulinasRESUMO
OBJECTIVES: The predictors of SARS-CoV-2 reinfection are unclear. We examined predictors of reinfection with pre-Omicron and Omicron variants among COVID-19-recovered individuals. METHODS: Randomly selected COVID-19-recovered patients (N = 1004) who donated convalescent plasma during 2020 were interviewed between August 2021 and March 2022 regarding COVID-19 vaccination and laboratory-proven reinfection. The sera from 224 (22.3%) participants were tested for antispike (anti-S) immunoglobulin G and neutralizing antibodies. RESULTS: The participants' median age was 31.1 years (78.6% males). The overall reinfection incidence rate was 12.8%; 2.7% versus 21.6% for the pre-Omicron (mostly Delta) versus Omicron variants. Negative associations were found between fever during the first illness and pre-Omicron reinfection: relative risk 0.29 (95% confidence interval 0.09-0.94), high anti-N level at first illness and Omicron reinfection: 0.53 (0.33-0.85), and overall reinfection: 0.56 (0.37-0.84), as well as between subsequent COVID-19 vaccination with the BNT162b2 vaccine and pre-Omicron 0.15 (0.07-0.32), Omicron 0.48 (0.25-0.45), and overall reinfections 0.38 (0.25-0.58). These variables significantly correlated with immunoglobulin G anti-S follow-up levels. High pre-existing anti-S binding and neutralizing antibody levels against the SARS-CoV-2 Wuhan and Alpha strains predicted protection against Omicron reinfections. CONCLUSION: Strong immune responses after the first COVID-19 infection and subsequent vaccination with the BNT162b2 vaccine provided cross-protection against reinfections with the Delta and Omicron variants.
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COVID-19 , Masculino , Humanos , Adulto , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Vacina BNT162 , Reinfecção/epidemiologia , Vacinas contra COVID-19 , Soroterapia para COVID-19 , Anticorpos Neutralizantes , Imunoglobulina G , Anticorpos AntiviraisRESUMO
Background: Group B streptococcus (GBS) harbors many virulence factors but there is limited data regarding their importance in colonization in pregnancy and early-onset disease (EOD) in the newborn. We hypothesized that colonization and EOD are associated with different distribution and expression of virulence factors. Methods: We studied 36 GBS EOD and 234 GBS isolates collected during routine screening. Virulence genes (pilus-like structures-PI-1, PI-2a, PI-2b; rib and hvgA) presence and expression were identified by PCR and qRT-PCR. Whole genome sequencing (WGS) and comparative genomic analyses were used to compare coding sequences (CDSs) of colonizing and EOD isolates. Results: Serotype III (ST17) was significantly associated with EOD and serotype VI (ST1) with colonization. hvgA and rib genes were more prevalent among EOD isolates (58.3 and 77.8%, respectively; p < 0.01). The pilus loci PI-2b and PI-2a were more prevalent among EOD isolates (61.1%, p < 0.01), while the pilus loci PI-2a and PI-1 among colonizing isolates (89.7 and 93.1% vs. 55.6 and 69.4%, p < 0.01). qRT PCR analysis revealed that hvgA was barely expressed in colonizing isolates, even though the gene was detected. Expression of the rib gene and PI-2b was two-fold higher in EOD isolates compared to colonizing isolates. Transcription of PI-2a was three-fold higher in colonizing isolates compared to EOD isolates. ST17 isolates (associated with EOD) had a smaller genome size compared ST1 and the genome was more conserved relative to the reference strain and ST17 isolates. In a multivariate logistic regression analysis virulence factors independently associated with EOD were serotype 3, and PI-1 and PI-2a was protective. Conclusion: There was a significant difference in the distribution of hvg A, rib, and PI genes among EOD (serotype III/ST17) and colonizing (serotype VI/ST1) isolates suggesting an association between invasive disease and these virulence factors. Further study is needed to understand the contribution of these genes to GBS virulence.
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BACKGROUND: Waning immunity and an increased incidence of coronavirus disease 2019 (COVID-19) during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth vaccine dose for high-risk individuals. In this study, we assessed its effect for hospitalized patients with severe breakthrough COVID-19. METHODS: In this multicenter cohort study of hospitalized adults with severe COVID-19 in Israel, from 15 to 31 January 2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death and was compared between 3- and 4-dose vaccinees using logistic regression. RESULTS: Included were 1049 patients, median age 80 years. Among them, 394 were unvaccinated, 386 and 88 had received 3 or 4 doses, respectively. The 3-dose group was older, included more males, and immunosuppressed patients but with similar outcomes, 49% vs 51% compared with unvaccinated patients (P = .72). Patients who received 4 doses were similarly older and immunosuppressed but had better outcomes compared with unvaccinated patients, 34% vs 51% (P < .01). We examined independent predictors for poor outcome in patients who received either 3 or 4 doses a median of 161 days or 14 days before diagnosis, respectively. Receipt of the fourth dose was associated with protection (odds ratio, 0.51; 95% confidence interval, .3-.87), as was remdesivir. Male sex, chronic renal failure, and dementia were associated with poor outcomes. CONCLUSIONS: Among hospitalized patients with severe breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death compared with 3 doses.
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COVID-19 , Vacinas , Adulto , Humanos , Masculino , Idoso de 80 Anos ou mais , Israel/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Mortalidade HospitalarRESUMO
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.
RESUMO
Highly variable estimates of COVID-19-associated fungal diseases (IFDs) have been reported. We aimed to determine the incidence of clinically important fungal diseases in hospitalized COVID-19 patients during the first year of the pandemic. We performed a multicenter survey of IFDs among patients hospitalized with COVID-19 in 13 hospitals in Israel between February 2020 and May 2021. COVID-19-associated pulmonary mold disease (PMD) and invasive candidiasis (IC) were defined using ECMM/ISHAM and EORTC/MSG criteria, respectively. Overall rates of IC and PMD among patients with critical COVID-19 were 10.86 and 10.20 per 1000 admissions, respectively, with significant variability among medical centers. PMD rates were significantly lower in centers where galactomannan was a send-out test versus centers with on-site testing (p = 0.035). The 30-day mortality rate was 67.5% for IC and 57.5% for PMD. Treatment with an echinocandin for IC or an extended-spectrum azole for PMD was associated with significantly lower mortality rates (adjusted hazard ratio [95% confidence interval], 0.26 [0.07-0.91] and 0.23 [0.093-0.57], respectively). In this multicenter national survey, variable rates of PMD were associated with on-site galactomannan testing, suggesting under-detection in sites lacking this capacity. COVID-19-related IFDs were associated with high mortality rates, which were reduced with appropriate antifungal therapy.