To investigate whether ProVate™, a novel, disposable, self-inserted vaginal device for pelvic org... more To investigate whether ProVate™, a novel, disposable, self-inserted vaginal device for pelvic organ prolapse management, clinically affects the vaginal micro ora, as compared with a commercially available ring pessary, in order to assess its microbiological safety. Methods This interventional, prospective, multi-center, open-label, randomized, controlled, statistically powered (non-inferiority), home-use, cross-over study was conducted at seven sites. Participants were randomized into either group A (using ProVate™ and then a new reusable commercially available ring pessary [control]) or B (using control device and then ProVate™) with a 1:1 ratio. Primary endpoint was based on meeting one of the failure criteria: signi cant change in Lactobacillus spp., Gardnerella vaginalis, Candida morphotypes, or Staphylococcus aureus levels compared to the baseline (signi cant change: Nugent score ≥ 7 or > 1 scale unit increase in S. aureus or Candida morphotype), bothersome vaginal symptoms, or symptoms requiring treatment. Results The study included 58 participants (mean age: 64.5 years, 91.4% post-menopausal). The failure rate was 15.5% for ProVate™ and control groups while using 383 ProVate™ devices over 1,647 days or one control device throughout the study. Two patients had bothersome vaginal complaints and one had vaginal infection in the control group, but no such cases were observed in the ProVate™ group. Conclusion The primary endpoint of possible vaginal microbial changes, bothersome vaginal symptoms, or treatment-requiring vaginal complaints while using ProVate™ was successfully met. Our ndings show that the vaginal micro ora is comparable when using either ProVate™ or commercially available ring pessary (control) with a relatively low rate of vaginal infections. Trial registration details ClinicalTrials.gov; What does this study add to the clinical work? The study provides new insight into the variations of vaginal micro ora while using pessaries in general. It demonstrates that the new, disposable, single-use ProVate ring pessary and a new, unused commercially available reusable pessary do not have any clinically meaningful impact on the vaginal micro ora and are safe for use.
The antibacterial activity of many antibiotics is impaired by unfavorable conditions that prevail... more The antibacterial activity of many antibiotics is impaired by unfavorable conditions that prevail at infectious sites [1]. Among these conditions, low pH [2,3], anaerobiasis [2±4], discrepancies between minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) [5], the presence of a foreign body, albumin, globulin [6], pus [7] and dead bacteria are known to be important factors. Fluoroquinolones may be of interest in this respect as the antibacterial activity of these compounds is minimally affected by such adverse conditions compared to aminoglycosides, macrolides and the b-lactam antibiotics. The aim of this investigation was to study the effect of albumin, globulin, pus and dead bacteria on the antibacterial activity of moxi¯oxacin, trova¯oxacin and cipro¯oxacin in concentrations of 0.25±16 MICs against Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli.
Influenza A and other respiratory viruses, circulate each winter and cause respiratory illness th... more Influenza A and other respiratory viruses, circulate each winter and cause respiratory illness that can lead to severe complications in hospitalized patients. During the COVID-19 pandemic, only a few cases of respiratory viruses were detected in Israel. Our study applied RT-PCR to examine 13,674 samples collected from patients hospitalized with respiratory symptoms in 2019, 2020, and 2021 and the first half of the 2022 winter. A sharp increase in influenza A(H3N2) cases was observed in winter 2021-2022 as compared to 2020, followed by a sudden decrease in influenza cases after the detection of the SARS-CoV-2 omicron variant in Israel. Comparison of the area under the curve (AUC) of influenza infection rates during 7 consecutive winter seasons found that the minimal AUC between 2015 and 2020 was 281.1, while in 2021-2022, it was significantly lower (162.6 AUC; p = 0.0017), although the percentage of positive influenza cases was similar to those of previous years. The presented findin...
Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneum... more Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneumoniae carbapenemase (bla KPC) enzymes are among the most common -lactamases described. In this study, we report the development and validation of a real-time PCR (q-PCR) assay for the detection of bla KPC genes using TaqMan chemistry. The q-PCR amplification of bla KPC DNA was linear over 7 log dilutions (r 2 ؍ 0.999; slope, 3.54), and the amplification efficiency was 91.6%. The q-PCR detection limit was 1 CFU, and there was no cross-reaction with DNA extracted from several multidrug-resistant bacteria. Perianal/rectal swabs (n ؍ 187) collected in duplicate from 128 patients admitted to Sheba Medical Center surgical intensive care units were evaluated for the presence of carbapenem-resistant bacteria by culturing on MacConkey agar-pluscarbapenem disks and for bla KPC genes by q-PCR. Carbapenem-resistant organisms, all K. pneumoniae, were isolated from 47 (25.1%) of the 187 samples collected, while bla KPC genes were detected in 54 (28.9%) of the patient samples extracted by the NucliSENS easyMAG system. Of these, seven samples were positive for bla KPC genes by q-PCR but negative for carbapenem resistance by culture, while all samples in which no carbapenemresistant bacteria were detected by culture also tested negative by q-PCR. Thus, the sensitivity and specificity of the q-PCR assay after extraction by the NucliSENS easyMAG system were 100% and 95%, respectively. Similar values were obtained after DNA extraction by the Roche MagNA Pure LC instrument: 97.9% sensitivity and 96.4% specificity. Overall, the bla KPC q-PCR assay appears to be highly sensitive and specific. The utilization of q-PCR will shorten the time to bla KPC detection from 24 h to 4 h and will help in rapidly isolating colonized or infected patients and assigning them to cohorts.
SUMMARYThe aim of the present study was to assess the recent trends in the epidemiology of non-ty... more SUMMARYThe aim of the present study was to assess the recent trends in the epidemiology of non-typhoidSalmonellain Israel using a sentinel laboratory-based surveillance network. Between 1999 and 2009, 8758Salmonellastool isolates were reported by five sentinel laboratories. There was a significant decrease in the incidence rate ofSalmonellaisolates from 70·5/100 000 in 1999 to 21·6/100 000 in 2005 followed by a slight increase to 30·3/100 000 in 2009. Of allSalmonella, 64·3% were isolated from children in the 0–4 years age group. Up to 2008,S. Enteritidis was the most prevalent serotype and in 2009S. Infantis emerged as the most commonSalmonellaserotype. The decrease in the incidence ofS. Enteritidis andS. Typhimurium and increase inS. Infantis among humans were associated with a similar trend among breeding flocks, which followed significant preventive interventions conducted againstS. Enteritidis andS. Typhimurium infections in poultry. Tight surveillance and education of food han...
The emergence of fluconazole-resistant Candida (FRC) is worrisome, but little is known about susc... more The emergence of fluconazole-resistant Candida (FRC) is worrisome, but little is known about susceptibility patterns in different nosocomial settings. We prospectively analysed Candida bloodstream isolates in 18 medical centres in Israel (six tertiary-care and 12 community hospitals). The study included 444 episodes of candidaemia (450 patient-specific isolates, 8.5% fluconazole-resistant). Institutional FRC bloodstream infection rates correlated with annual inpatient days, and were strongly associated with the presence and activity of haematology/oncology services. Infection with Candida krusei and fluconazole-resistant Candida glabrata occurred exclusively in hospitals with >600 beds. These findings suggest that empirical antifungal strategies should be tailored to the nosocomial setting.
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by impai... more Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by impaired microbial killing and susceptibility to bacterial and fungal infections. Cure of the disease can be achieved by stem cell transplantation when performed early in its course, and before severe infections have developed. Invasive aspergillosis constitutes a very high risk for transplantation. We report a 4-year-old boy with Xlinked CGD who underwent successful HLA-identical peripheral blood stem cell (PBSC) transplantation during invasive pulmonary aspergillosis and osteomyelitis of the left fourth rib, which was unresponsive to antifungal treatment. During the 2 months prior to the transplant he received G-CSF-mobilized granulocyte transfusions (GTX) from unrelated donors three times a week in addition to the antifungal treatment. This resulted in clinical improvement in his respiratory status. He also received GTX during the aplastic period after the conditioning regimen, until he had engrafted. Post-transplant superoxide generation test revealed that neutrophil function was within normal range. One year post transplant the CT scan showed almost complete clearance of the pulmonary infiltrates and a marked improvement in the osteomyelitic process. Based on other reports and our own experience, GTX can serve as important treatment in patients with CGD who have failed conventional anti-fungal treatment and for whom stem cell transplantation is the only chance for cure.
Background: Invasive mold infections (IMIs) are a leading cause of mortality among immunocompromi... more Background: Invasive mold infections (IMIs) are a leading cause of mortality among immunocompromised patients. Isavuconazole is a new drug that shows promise in the adult population for the treatment of IMIs. No data regarding the use of isavuconazole in pediatric patients have been published. Methods: Patients with a diagnosis of IMI from our pediatric hemato-oncology division, treated with isavuconazole between 2010 and 2016, were identified using the hospital's computerized database. Data including demographics, clinical course, and outcome were collected. Pharmacokinetic samples were obtained from two younger patients to guide dosing. Results: In total, three patients (4.5, 5, and 19 years of age) with invasive mucormycosis who were treated with isavuconazole were identified. All patients were treated with isavuconazole as a second line therapy and experienced improvement following the initiation of this treatment. Conclusions: Based on our limited clinical experience, isavuconazole may be a safe and effective treatment option for children and adolescents afflicted by IMI. Prospective clinical trials should be performed in order to evaluate the pharmakokinetics and safety of isavuconazole in the pediatric population.
A patient transferred from South Africa to Israel acquired a Candida auris infection. Phylogeneti... more A patient transferred from South Africa to Israel acquired a Candida auris infection. Phylogenetic analysis showed resemblance of C. auris to isolates from South Africa but not Israel, suggesting travel-associated infection. C. auris infection occurred weeks later in another patient at the same hospital, suggesting prolonged environmental persistence.
Background. Listeria monocytogenes is a foodborne pathogen that causes life-threatening infection... more Background. Listeria monocytogenes is a foodborne pathogen that causes life-threatening infections in elderly, immunocompromised, and pregnant women. In pregnancy it may cause fetal loss or a preterm delivery, and the neonate is prone to neonatal sepsis and death. Methods. We created a cohort of all L. monocytogenes cases during 10 years (1998-2007) in Israel, by a comprehensive review of cases in hospitals throughout the country and cases reported to the Ministry of Health. Results. One hundred sixty-six pregnancy-related listeriosis cases were identified, resulting in a yearly incidence of 5-25 cases per 100 000 births. Presentation associated with fetal demise was more common in the second trimester (55.3%), and preterm labor (52.3%) and abnormal fetal heart rate monitoring (22.2%) were more common in the third trimester (P = .001). Fetal viability was low in the second trimester (29.2%) and much higher (95.3%) in the third trimester. Each additional week of pregnancy increased the survival chance by 33% (odds ratio, 1.331 [95% confidence interval, 1.189-1.489]). A single case of maternal mortality was identified. Listeria monocytogenes serotype 4b was more common in pregnancy-related than in non-pregnancy-related cases (79.5% vs 61.3%, P = .011). Pulsed-field gel electrophoresis analysis suggested that 1 pulsotype is responsible for 35.7% of the pregnancy cases between 2001 and 2007. This clone is closely related to the Italian gastroenteritis-associated HPB2262 and the invasive US Scott A L. monocytogenes strains. Conclusions. Our survey emphasizes the high rate of pregnancy-related listeriosis in Israel and shows that specific clones might account for this.
The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxac... more The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxacin) on capsular polysaccharide distribution and on opsonophagocytosis by human polymorphonuclear leukocytes of unencapsulated and encapsulated Escherichia coli strains was studied. Unencapsulated E. coli strains were readily opsonized in serum and easily ingested by polymorphonuclear leukocytes, and antibiotics did not further enhance the phagocytosis rates. In contrast, encapsulated bacteria were poorly opsonized in human serum, and phagocytosis was enhanced after overnight exposure to 0.5x the MICs of the antibiotics, with the exception of cefepime. Incubation of unencapsulated as well as encapsulated bacteria in complement-inactivated serum markedly reduced the bacterial uptake by polymorphonuclear leukocytes regardless of the presence of antibiotics. Slide agglutination assays, performed either with a monoclonal antibody for capsular polysaccharide or with an antiserum raised against...
Background: Malarial infection in pregnancy is uncommon in the United States but morbidity and mo... more Background: Malarial infection in pregnancy is uncommon in the United States but morbidity and mortality can be striking. "Severe" malarial infections in pregnancy are even rarer, with only eight reported cases in 2010. Primiparous women are at the greatest risk for significant parasitemia. Case Presentation: A 33-year-old Nigerian G4P3003 at 34 and 2 weeks gestational age presents with a five day history of fevers, frontal headache, weakness, and diarrhea in setting of recent immigration to America. She was septic in the emergency room, with marked splenomegaly, thrombocytopenia, and electrolyte disturbances, requiring medical intensive care unit stabilization and treatment for Plasmodium falciparum malaria sepsis. After stabilization, continuous electronic fetal monitoring revealed multiple prolonged decelerations requiring delivery for fetal indications. Conclusion: Malarial infection in pregnancy, although rare, is often caused by the most virulent species, Plasmodium falciparum, and decompensation can occur quickly more commonly in first pregnancies. "Severe" malarial infections in pregnancy with documentation through the postpartum course are exceedingly rare in the United States.
SUMMARYThe incidence of invasive infections due toNeisseria meningitidisin Israel is about 1/100 ... more SUMMARYThe incidence of invasive infections due toNeisseria meningitidisin Israel is about 1/100 000 population annually. Three cases of meningococcal meningitis were reported in employees at a single plant; the first case appeared in March 2013 and the second and third cases appeared in December, almost 9 months later.N. meningitidisserogroup B was isolated from cerebrospinal fluid samples. Multilocus sequence typing assigned the three meningococcal isolates to ST10418, a new sequence type and a member of the ST32 clonal complex. The clonality was confirmed by performance of pulsed-field gel electrophoresis. Post-exposure antibiotic prophylaxis was administered to close contacts of the first case. Upon the diagnosis of the additional two cases, post-exposure prophylaxis was administered to all the plant employees. This report demonstrates the importance of combining public health measures and advanced laboratory studies to confirm clonality and to prevent further disease spread in ...
Bone allografting is the most common form of allotransplantation in modern medicine. Bone banking... more Bone allografting is the most common form of allotransplantation in modern medicine. Bone banking is usually the major part of most tissue banks throughout the world. Several years ago, many standards of bone banking were set empirically, and have never been evaluated. One particular parameter or standard was outdating graft materials after 5 years of storage. This study was conducted to evaluate the effect of prolonged cryopreservation on the biomechanical properties of bone allografts and establish whether graft materials become contaminated during long-term storage.Proximal humeral bone allografts were obtained from the bone bank after 1, 3 and 5 years of -80 degrees C cryopreservation. Samples of each humeral head, i.e., cartilage, subchondral bone and spongy bone were histologically examined for inter- and intra-cellular changes. A three-point mechanical bending test was used on identical pieces of cortical bone to compare fresh and cryopreserved materials. Fresh-retrieved cort...
An ongoing nationwide prospective surveillance study was initiated in Israel in October, 1988, to... more An ongoing nationwide prospective surveillance study was initiated in Israel in October, 1988, to document childhood invasive infections caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis. This study enabled us to document the effect on childhood invasive Hib disease of the introduction of conjugate Hib vaccines to Israel. The incidence of invasive Hib disease before the age of 5 years dropped from 34 per 100000 before initiation of immunization to < 5 per 100000 in 1995 and is projected to be <4 in 1996. After <2 years, when various conjugate vaccines had been available in the private sector alone and had achieved partial coverage only, the Israeli Ministry of Health decided to add Hib conjugate vaccine to the regular infant immunization program, free of charge, effective for all infants born after January 1, 1994. The vaccine chosen was Hib polysaccharide linked to outer membrane protein complex of N. meningitidis B. Vaccine coverage has exceeded 90% of all infants born since January 1, 1994. Efficacy and effectiveness during the first 34 months of the program (January 1, 1994, to October 31, 1996) were 95.4 and 99.7%, respectively, for all invasive Hib disease and 97 and 99.4%, respectively, for Hib meningitis. The described ongoing surveillance program showed the existence and extent of Hib problems in Israel and documented the success of the immunization program in essentially eliminating the disease in Israel.
The failure of antibiotic treatment to eradicate group-A streptococci in up to 30% of patients wi... more The failure of antibiotic treatment to eradicate group-A streptococci in up to 30% of patients with pharyngotonsillitis is unexplained. Some strains of group-A streptococci can enter respiratory epithelial cells, where they would be inaccessible to antibiotics unable to penetrate the cell membrane, such as penicillins. The fibronectin-binding proteins, F1 and SfbI, are needed for this process. We hypothesised, therefore, that an intracellular reservoir of group-A streptococci could account, at least partly, for failure to eradicate throat carriage, and that the presence of the gene for fibronectin-binding protein (F1) might be linked to the ability of a strain to persist in the throat after therapy. We investigated the frequency of prtF1-containing strains among 67 patients with pharyngotonsillitis. All patients were clinically cured, although 13 of them continued to carry group-A streptococci in the throat during or after therapy. To distinguish between persisting and recolonising strains, isolates from the 13 patients were serologically tested and compared by polymorphic DNA-amplification technique. 12 (92%) of the 13 patients with symptomless carriage had prtF1-containing strains in the throat, compared with 16 (30%) of the 54 patients with successful eradication (p=0.0001). Three of the 13 eradication-failure patients were recolonised with strains that differed from the pretreatment strains. Nine of the ten (90%) persisting strains carried prtF1 (p=0.0009). Our findings suggest that protein-F1-mediated entry to cells is involved in the causative process of the carriage state.
Purpose: To determine the effect of isolation rooms on the direct spread of nosocomial infections... more Purpose: To determine the effect of isolation rooms on the direct spread of nosocomial infections (NIs) owing to cross-colonization in a pediatric intensive care unit (PICU). Materials and Methods: This 6-month comparative clinical study used retrospective data from 1992 (an open single-space unit) and prospective surveillance from 1995 (individual rooms) to assess the effectiveness of the latter design on the control of NIs in critically ill pediatric patients. Patients admitted to the PICU for at least 48 hours underwent a microbiologic survey. Results: The average number of NIs per patient was higher in 1992 (3.62 Ϯ 0.7, 78 patients) compared with 1995 (1.87 Ϯ 0.2, 115 patients). Bacterial NIs were caused by gram-positive cocci (33.3%) and aerobic gram-negative bacilli (66.6%). Fungemia in all cases was caused by Candida albicans. Similarly, length of stay was significantly higher in 1992 compared with 1995 (25 Ϯ 6 and 11 Ϯ 6 days, respectively; P Ͻ .05). There was a significant reduction of respiratory and urinary tract episodes of NI as well as catheter-related infections in the separate room arrangement. Conclusions: Our preliminary analysis suggests a possible beneficial effect of single isolation rooms in reducing NI rate in the PICU. Hence, the influence of room isolation on NIs in pediatric intensive care warrants further investigation.
Background Burkholderia cepacia is a common environmental bacterium that is resistant to disinfec... more Background Burkholderia cepacia is a common environmental bacterium that is resistant to disinfectants, and therefore is often encountered as a hospital-acquired pathogen. We describe an outbreak of B. cenocepacia bacteremia among hospitalized oncology patients. Methods A matched case-control study and an extensive environmental investigation were conducted. Species were identified by RFLP of the amplified recA gene. DNA was fingerprinted by pulsed-field gel electrophoresis (PFGE). Results Between November 2005 and September 2006, B. cenocepacia bacteremia developed in 17 patients with underlying malignancy of whom 14 had tunneled central venous catheters. All patients had fever and chills which subsided following removal of the central catheter and administration of ceftazidime. Extensive epidemiological investigation could not find a common source for the outbreak. Patients were hospitalized in three different buildings with different health care personnel. Medications were prepared in different sites by different personnel. A multivariate analysis demonstrated that the independent risk factors for developing nosocomial B. cenocepacia bacteremia were hospitalization at the center for long-term support (OR 28.8; 95% CI 1.83-453.4) and reduced use of antibiotics during the last month (OR 0.07; 95% CI 0.01-0.40). All isolates had identical antimicrobial susceptibility; PFGE indicated that a complex of closely related strains was involved in the outbreak. All isolates were identified as B. cenocepacia, known to infect cystic fibrosis patients. Strict infection control measures terminated the outbreak. Conclusions B. cenocepacia is an emerging nosocomial pathogen among oncology patients.
To investigate whether ProVate™, a novel, disposable, self-inserted vaginal device for pelvic org... more To investigate whether ProVate™, a novel, disposable, self-inserted vaginal device for pelvic organ prolapse management, clinically affects the vaginal micro ora, as compared with a commercially available ring pessary, in order to assess its microbiological safety. Methods This interventional, prospective, multi-center, open-label, randomized, controlled, statistically powered (non-inferiority), home-use, cross-over study was conducted at seven sites. Participants were randomized into either group A (using ProVate™ and then a new reusable commercially available ring pessary [control]) or B (using control device and then ProVate™) with a 1:1 ratio. Primary endpoint was based on meeting one of the failure criteria: signi cant change in Lactobacillus spp., Gardnerella vaginalis, Candida morphotypes, or Staphylococcus aureus levels compared to the baseline (signi cant change: Nugent score ≥ 7 or > 1 scale unit increase in S. aureus or Candida morphotype), bothersome vaginal symptoms, or symptoms requiring treatment. Results The study included 58 participants (mean age: 64.5 years, 91.4% post-menopausal). The failure rate was 15.5% for ProVate™ and control groups while using 383 ProVate™ devices over 1,647 days or one control device throughout the study. Two patients had bothersome vaginal complaints and one had vaginal infection in the control group, but no such cases were observed in the ProVate™ group. Conclusion The primary endpoint of possible vaginal microbial changes, bothersome vaginal symptoms, or treatment-requiring vaginal complaints while using ProVate™ was successfully met. Our ndings show that the vaginal micro ora is comparable when using either ProVate™ or commercially available ring pessary (control) with a relatively low rate of vaginal infections. Trial registration details ClinicalTrials.gov; What does this study add to the clinical work? The study provides new insight into the variations of vaginal micro ora while using pessaries in general. It demonstrates that the new, disposable, single-use ProVate ring pessary and a new, unused commercially available reusable pessary do not have any clinically meaningful impact on the vaginal micro ora and are safe for use.
The antibacterial activity of many antibiotics is impaired by unfavorable conditions that prevail... more The antibacterial activity of many antibiotics is impaired by unfavorable conditions that prevail at infectious sites [1]. Among these conditions, low pH [2,3], anaerobiasis [2±4], discrepancies between minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) [5], the presence of a foreign body, albumin, globulin [6], pus [7] and dead bacteria are known to be important factors. Fluoroquinolones may be of interest in this respect as the antibacterial activity of these compounds is minimally affected by such adverse conditions compared to aminoglycosides, macrolides and the b-lactam antibiotics. The aim of this investigation was to study the effect of albumin, globulin, pus and dead bacteria on the antibacterial activity of moxi¯oxacin, trova¯oxacin and cipro¯oxacin in concentrations of 0.25±16 MICs against Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli.
Influenza A and other respiratory viruses, circulate each winter and cause respiratory illness th... more Influenza A and other respiratory viruses, circulate each winter and cause respiratory illness that can lead to severe complications in hospitalized patients. During the COVID-19 pandemic, only a few cases of respiratory viruses were detected in Israel. Our study applied RT-PCR to examine 13,674 samples collected from patients hospitalized with respiratory symptoms in 2019, 2020, and 2021 and the first half of the 2022 winter. A sharp increase in influenza A(H3N2) cases was observed in winter 2021-2022 as compared to 2020, followed by a sudden decrease in influenza cases after the detection of the SARS-CoV-2 omicron variant in Israel. Comparison of the area under the curve (AUC) of influenza infection rates during 7 consecutive winter seasons found that the minimal AUC between 2015 and 2020 was 281.1, while in 2021-2022, it was significantly lower (162.6 AUC; p = 0.0017), although the percentage of positive influenza cases was similar to those of previous years. The presented findin...
Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneum... more Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneumoniae carbapenemase (bla KPC) enzymes are among the most common -lactamases described. In this study, we report the development and validation of a real-time PCR (q-PCR) assay for the detection of bla KPC genes using TaqMan chemistry. The q-PCR amplification of bla KPC DNA was linear over 7 log dilutions (r 2 ؍ 0.999; slope, 3.54), and the amplification efficiency was 91.6%. The q-PCR detection limit was 1 CFU, and there was no cross-reaction with DNA extracted from several multidrug-resistant bacteria. Perianal/rectal swabs (n ؍ 187) collected in duplicate from 128 patients admitted to Sheba Medical Center surgical intensive care units were evaluated for the presence of carbapenem-resistant bacteria by culturing on MacConkey agar-pluscarbapenem disks and for bla KPC genes by q-PCR. Carbapenem-resistant organisms, all K. pneumoniae, were isolated from 47 (25.1%) of the 187 samples collected, while bla KPC genes were detected in 54 (28.9%) of the patient samples extracted by the NucliSENS easyMAG system. Of these, seven samples were positive for bla KPC genes by q-PCR but negative for carbapenem resistance by culture, while all samples in which no carbapenemresistant bacteria were detected by culture also tested negative by q-PCR. Thus, the sensitivity and specificity of the q-PCR assay after extraction by the NucliSENS easyMAG system were 100% and 95%, respectively. Similar values were obtained after DNA extraction by the Roche MagNA Pure LC instrument: 97.9% sensitivity and 96.4% specificity. Overall, the bla KPC q-PCR assay appears to be highly sensitive and specific. The utilization of q-PCR will shorten the time to bla KPC detection from 24 h to 4 h and will help in rapidly isolating colonized or infected patients and assigning them to cohorts.
SUMMARYThe aim of the present study was to assess the recent trends in the epidemiology of non-ty... more SUMMARYThe aim of the present study was to assess the recent trends in the epidemiology of non-typhoidSalmonellain Israel using a sentinel laboratory-based surveillance network. Between 1999 and 2009, 8758Salmonellastool isolates were reported by five sentinel laboratories. There was a significant decrease in the incidence rate ofSalmonellaisolates from 70·5/100 000 in 1999 to 21·6/100 000 in 2005 followed by a slight increase to 30·3/100 000 in 2009. Of allSalmonella, 64·3% were isolated from children in the 0–4 years age group. Up to 2008,S. Enteritidis was the most prevalent serotype and in 2009S. Infantis emerged as the most commonSalmonellaserotype. The decrease in the incidence ofS. Enteritidis andS. Typhimurium and increase inS. Infantis among humans were associated with a similar trend among breeding flocks, which followed significant preventive interventions conducted againstS. Enteritidis andS. Typhimurium infections in poultry. Tight surveillance and education of food han...
The emergence of fluconazole-resistant Candida (FRC) is worrisome, but little is known about susc... more The emergence of fluconazole-resistant Candida (FRC) is worrisome, but little is known about susceptibility patterns in different nosocomial settings. We prospectively analysed Candida bloodstream isolates in 18 medical centres in Israel (six tertiary-care and 12 community hospitals). The study included 444 episodes of candidaemia (450 patient-specific isolates, 8.5% fluconazole-resistant). Institutional FRC bloodstream infection rates correlated with annual inpatient days, and were strongly associated with the presence and activity of haematology/oncology services. Infection with Candida krusei and fluconazole-resistant Candida glabrata occurred exclusively in hospitals with >600 beds. These findings suggest that empirical antifungal strategies should be tailored to the nosocomial setting.
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by impai... more Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by impaired microbial killing and susceptibility to bacterial and fungal infections. Cure of the disease can be achieved by stem cell transplantation when performed early in its course, and before severe infections have developed. Invasive aspergillosis constitutes a very high risk for transplantation. We report a 4-year-old boy with Xlinked CGD who underwent successful HLA-identical peripheral blood stem cell (PBSC) transplantation during invasive pulmonary aspergillosis and osteomyelitis of the left fourth rib, which was unresponsive to antifungal treatment. During the 2 months prior to the transplant he received G-CSF-mobilized granulocyte transfusions (GTX) from unrelated donors three times a week in addition to the antifungal treatment. This resulted in clinical improvement in his respiratory status. He also received GTX during the aplastic period after the conditioning regimen, until he had engrafted. Post-transplant superoxide generation test revealed that neutrophil function was within normal range. One year post transplant the CT scan showed almost complete clearance of the pulmonary infiltrates and a marked improvement in the osteomyelitic process. Based on other reports and our own experience, GTX can serve as important treatment in patients with CGD who have failed conventional anti-fungal treatment and for whom stem cell transplantation is the only chance for cure.
Background: Invasive mold infections (IMIs) are a leading cause of mortality among immunocompromi... more Background: Invasive mold infections (IMIs) are a leading cause of mortality among immunocompromised patients. Isavuconazole is a new drug that shows promise in the adult population for the treatment of IMIs. No data regarding the use of isavuconazole in pediatric patients have been published. Methods: Patients with a diagnosis of IMI from our pediatric hemato-oncology division, treated with isavuconazole between 2010 and 2016, were identified using the hospital's computerized database. Data including demographics, clinical course, and outcome were collected. Pharmacokinetic samples were obtained from two younger patients to guide dosing. Results: In total, three patients (4.5, 5, and 19 years of age) with invasive mucormycosis who were treated with isavuconazole were identified. All patients were treated with isavuconazole as a second line therapy and experienced improvement following the initiation of this treatment. Conclusions: Based on our limited clinical experience, isavuconazole may be a safe and effective treatment option for children and adolescents afflicted by IMI. Prospective clinical trials should be performed in order to evaluate the pharmakokinetics and safety of isavuconazole in the pediatric population.
A patient transferred from South Africa to Israel acquired a Candida auris infection. Phylogeneti... more A patient transferred from South Africa to Israel acquired a Candida auris infection. Phylogenetic analysis showed resemblance of C. auris to isolates from South Africa but not Israel, suggesting travel-associated infection. C. auris infection occurred weeks later in another patient at the same hospital, suggesting prolonged environmental persistence.
Background. Listeria monocytogenes is a foodborne pathogen that causes life-threatening infection... more Background. Listeria monocytogenes is a foodborne pathogen that causes life-threatening infections in elderly, immunocompromised, and pregnant women. In pregnancy it may cause fetal loss or a preterm delivery, and the neonate is prone to neonatal sepsis and death. Methods. We created a cohort of all L. monocytogenes cases during 10 years (1998-2007) in Israel, by a comprehensive review of cases in hospitals throughout the country and cases reported to the Ministry of Health. Results. One hundred sixty-six pregnancy-related listeriosis cases were identified, resulting in a yearly incidence of 5-25 cases per 100 000 births. Presentation associated with fetal demise was more common in the second trimester (55.3%), and preterm labor (52.3%) and abnormal fetal heart rate monitoring (22.2%) were more common in the third trimester (P = .001). Fetal viability was low in the second trimester (29.2%) and much higher (95.3%) in the third trimester. Each additional week of pregnancy increased the survival chance by 33% (odds ratio, 1.331 [95% confidence interval, 1.189-1.489]). A single case of maternal mortality was identified. Listeria monocytogenes serotype 4b was more common in pregnancy-related than in non-pregnancy-related cases (79.5% vs 61.3%, P = .011). Pulsed-field gel electrophoresis analysis suggested that 1 pulsotype is responsible for 35.7% of the pregnancy cases between 2001 and 2007. This clone is closely related to the Italian gastroenteritis-associated HPB2262 and the invasive US Scott A L. monocytogenes strains. Conclusions. Our survey emphasizes the high rate of pregnancy-related listeriosis in Israel and shows that specific clones might account for this.
The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxac... more The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxacin) on capsular polysaccharide distribution and on opsonophagocytosis by human polymorphonuclear leukocytes of unencapsulated and encapsulated Escherichia coli strains was studied. Unencapsulated E. coli strains were readily opsonized in serum and easily ingested by polymorphonuclear leukocytes, and antibiotics did not further enhance the phagocytosis rates. In contrast, encapsulated bacteria were poorly opsonized in human serum, and phagocytosis was enhanced after overnight exposure to 0.5x the MICs of the antibiotics, with the exception of cefepime. Incubation of unencapsulated as well as encapsulated bacteria in complement-inactivated serum markedly reduced the bacterial uptake by polymorphonuclear leukocytes regardless of the presence of antibiotics. Slide agglutination assays, performed either with a monoclonal antibody for capsular polysaccharide or with an antiserum raised against...
Background: Malarial infection in pregnancy is uncommon in the United States but morbidity and mo... more Background: Malarial infection in pregnancy is uncommon in the United States but morbidity and mortality can be striking. "Severe" malarial infections in pregnancy are even rarer, with only eight reported cases in 2010. Primiparous women are at the greatest risk for significant parasitemia. Case Presentation: A 33-year-old Nigerian G4P3003 at 34 and 2 weeks gestational age presents with a five day history of fevers, frontal headache, weakness, and diarrhea in setting of recent immigration to America. She was septic in the emergency room, with marked splenomegaly, thrombocytopenia, and electrolyte disturbances, requiring medical intensive care unit stabilization and treatment for Plasmodium falciparum malaria sepsis. After stabilization, continuous electronic fetal monitoring revealed multiple prolonged decelerations requiring delivery for fetal indications. Conclusion: Malarial infection in pregnancy, although rare, is often caused by the most virulent species, Plasmodium falciparum, and decompensation can occur quickly more commonly in first pregnancies. "Severe" malarial infections in pregnancy with documentation through the postpartum course are exceedingly rare in the United States.
SUMMARYThe incidence of invasive infections due toNeisseria meningitidisin Israel is about 1/100 ... more SUMMARYThe incidence of invasive infections due toNeisseria meningitidisin Israel is about 1/100 000 population annually. Three cases of meningococcal meningitis were reported in employees at a single plant; the first case appeared in March 2013 and the second and third cases appeared in December, almost 9 months later.N. meningitidisserogroup B was isolated from cerebrospinal fluid samples. Multilocus sequence typing assigned the three meningococcal isolates to ST10418, a new sequence type and a member of the ST32 clonal complex. The clonality was confirmed by performance of pulsed-field gel electrophoresis. Post-exposure antibiotic prophylaxis was administered to close contacts of the first case. Upon the diagnosis of the additional two cases, post-exposure prophylaxis was administered to all the plant employees. This report demonstrates the importance of combining public health measures and advanced laboratory studies to confirm clonality and to prevent further disease spread in ...
Bone allografting is the most common form of allotransplantation in modern medicine. Bone banking... more Bone allografting is the most common form of allotransplantation in modern medicine. Bone banking is usually the major part of most tissue banks throughout the world. Several years ago, many standards of bone banking were set empirically, and have never been evaluated. One particular parameter or standard was outdating graft materials after 5 years of storage. This study was conducted to evaluate the effect of prolonged cryopreservation on the biomechanical properties of bone allografts and establish whether graft materials become contaminated during long-term storage.Proximal humeral bone allografts were obtained from the bone bank after 1, 3 and 5 years of -80 degrees C cryopreservation. Samples of each humeral head, i.e., cartilage, subchondral bone and spongy bone were histologically examined for inter- and intra-cellular changes. A three-point mechanical bending test was used on identical pieces of cortical bone to compare fresh and cryopreserved materials. Fresh-retrieved cort...
An ongoing nationwide prospective surveillance study was initiated in Israel in October, 1988, to... more An ongoing nationwide prospective surveillance study was initiated in Israel in October, 1988, to document childhood invasive infections caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis. This study enabled us to document the effect on childhood invasive Hib disease of the introduction of conjugate Hib vaccines to Israel. The incidence of invasive Hib disease before the age of 5 years dropped from 34 per 100000 before initiation of immunization to < 5 per 100000 in 1995 and is projected to be <4 in 1996. After <2 years, when various conjugate vaccines had been available in the private sector alone and had achieved partial coverage only, the Israeli Ministry of Health decided to add Hib conjugate vaccine to the regular infant immunization program, free of charge, effective for all infants born after January 1, 1994. The vaccine chosen was Hib polysaccharide linked to outer membrane protein complex of N. meningitidis B. Vaccine coverage has exceeded 90% of all infants born since January 1, 1994. Efficacy and effectiveness during the first 34 months of the program (January 1, 1994, to October 31, 1996) were 95.4 and 99.7%, respectively, for all invasive Hib disease and 97 and 99.4%, respectively, for Hib meningitis. The described ongoing surveillance program showed the existence and extent of Hib problems in Israel and documented the success of the immunization program in essentially eliminating the disease in Israel.
The failure of antibiotic treatment to eradicate group-A streptococci in up to 30% of patients wi... more The failure of antibiotic treatment to eradicate group-A streptococci in up to 30% of patients with pharyngotonsillitis is unexplained. Some strains of group-A streptococci can enter respiratory epithelial cells, where they would be inaccessible to antibiotics unable to penetrate the cell membrane, such as penicillins. The fibronectin-binding proteins, F1 and SfbI, are needed for this process. We hypothesised, therefore, that an intracellular reservoir of group-A streptococci could account, at least partly, for failure to eradicate throat carriage, and that the presence of the gene for fibronectin-binding protein (F1) might be linked to the ability of a strain to persist in the throat after therapy. We investigated the frequency of prtF1-containing strains among 67 patients with pharyngotonsillitis. All patients were clinically cured, although 13 of them continued to carry group-A streptococci in the throat during or after therapy. To distinguish between persisting and recolonising strains, isolates from the 13 patients were serologically tested and compared by polymorphic DNA-amplification technique. 12 (92%) of the 13 patients with symptomless carriage had prtF1-containing strains in the throat, compared with 16 (30%) of the 54 patients with successful eradication (p=0.0001). Three of the 13 eradication-failure patients were recolonised with strains that differed from the pretreatment strains. Nine of the ten (90%) persisting strains carried prtF1 (p=0.0009). Our findings suggest that protein-F1-mediated entry to cells is involved in the causative process of the carriage state.
Purpose: To determine the effect of isolation rooms on the direct spread of nosocomial infections... more Purpose: To determine the effect of isolation rooms on the direct spread of nosocomial infections (NIs) owing to cross-colonization in a pediatric intensive care unit (PICU). Materials and Methods: This 6-month comparative clinical study used retrospective data from 1992 (an open single-space unit) and prospective surveillance from 1995 (individual rooms) to assess the effectiveness of the latter design on the control of NIs in critically ill pediatric patients. Patients admitted to the PICU for at least 48 hours underwent a microbiologic survey. Results: The average number of NIs per patient was higher in 1992 (3.62 Ϯ 0.7, 78 patients) compared with 1995 (1.87 Ϯ 0.2, 115 patients). Bacterial NIs were caused by gram-positive cocci (33.3%) and aerobic gram-negative bacilli (66.6%). Fungemia in all cases was caused by Candida albicans. Similarly, length of stay was significantly higher in 1992 compared with 1995 (25 Ϯ 6 and 11 Ϯ 6 days, respectively; P Ͻ .05). There was a significant reduction of respiratory and urinary tract episodes of NI as well as catheter-related infections in the separate room arrangement. Conclusions: Our preliminary analysis suggests a possible beneficial effect of single isolation rooms in reducing NI rate in the PICU. Hence, the influence of room isolation on NIs in pediatric intensive care warrants further investigation.
Background Burkholderia cepacia is a common environmental bacterium that is resistant to disinfec... more Background Burkholderia cepacia is a common environmental bacterium that is resistant to disinfectants, and therefore is often encountered as a hospital-acquired pathogen. We describe an outbreak of B. cenocepacia bacteremia among hospitalized oncology patients. Methods A matched case-control study and an extensive environmental investigation were conducted. Species were identified by RFLP of the amplified recA gene. DNA was fingerprinted by pulsed-field gel electrophoresis (PFGE). Results Between November 2005 and September 2006, B. cenocepacia bacteremia developed in 17 patients with underlying malignancy of whom 14 had tunneled central venous catheters. All patients had fever and chills which subsided following removal of the central catheter and administration of ceftazidime. Extensive epidemiological investigation could not find a common source for the outbreak. Patients were hospitalized in three different buildings with different health care personnel. Medications were prepared in different sites by different personnel. A multivariate analysis demonstrated that the independent risk factors for developing nosocomial B. cenocepacia bacteremia were hospitalization at the center for long-term support (OR 28.8; 95% CI 1.83-453.4) and reduced use of antibiotics during the last month (OR 0.07; 95% CI 0.01-0.40). All isolates had identical antimicrobial susceptibility; PFGE indicated that a complex of closely related strains was involved in the outbreak. All isolates were identified as B. cenocepacia, known to infect cystic fibrosis patients. Strict infection control measures terminated the outbreak. Conclusions B. cenocepacia is an emerging nosocomial pathogen among oncology patients.
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