We sought to investigate the prevalence of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in men presenting to a sexually transmitted infection (STI) clinic, with special attention to M. genitalium, its occurrence in Israeli patients, coinfections, and risk factors. In a cross-sectional study, 259 men were successively enrolled in the Tel Aviv Levinsky Clinic for STIs between November 2008 and November 2010. There were 118 men with urethritis and 141 high-risk men without symptoms. M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis were detected using nucleic acid amplification tests. Demographic characteristics and risk factors were documented. The overall prevalence of infection with M. genitalium, C. trachomatis, N. gonorrhoeae, and T. vaginalis, were 6.6%, 12.7%, 23.1%, and 0%, respectively. Prevalences in men with urethritis were 11.9%, 22%, and 49%, for M. genitalium, C. trachomatis, and N. gonorrhoeae, respectively. Prevalences in men without symptoms were 2.1%, 5.0%, and 1.4%, for M. genitalium, C. trachomatis, and N. gonorrhoeae, respectively. Co-infections were found only in symptomatic individuals, in whom 5.9% were infected concomitantly with C. trachomatis and N. gonorrhoeae, and 2.5% had dual infection with M. genitalium and N. gonorrhoeae. N. gonorrhoeae, C. trachomatis, and M. genitalium were significantly more prevalent in patients with urethritis. M. genitalium was significantly more prevalent in the heterosexual population than in homosexual males. To conclude, we have found that M. genitalium infection is associated with urethritis in Israeli men, and more so in the heterosexual population. Testing men for M. genitalium as a cause of non-gonococcal urethritis is warranted, particularly because of its poor response to doxycycline and possible failure of azithromycin.

The current guidelines recommend culture and antibiotic susceptibility testing of Helicobacter pylori following two failed eradication attempts. Where testing is unavailable, epidemiological data for secondary H. pylori resistance are essential to allow for the rational use of antibiotics. The aim of this study was to describe the temporal changes in antibiotic resistance among adults previously treated for H. pylori infections and to identify predictors of resistance. Between 2007 and 2014, consecutive patients undergoing gastroscopy with H. pylori culture and susceptibility testing at our institution following at least two treatment failures were retrospectively identified. Antibiotic susceptibilities were recorded and linked to the demographic data. A total of 1,042 patients were identified, including 739 (70.9%) males, aged 39.3 ± 18.9 years. Resistance to clarithromycin, metronidazole, and levofloxacin was found in 57.2%, 64.4%, and 5.1% of isolates, respectively. Dual resistance to clarithromycin and metronidazole was seen in 39.9%. Over the study period, clarithromycin resistance increased annually in a linear manner (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03 to 1.14; P < 0.01), levofloxacin resistance decreased annually (OR, 0.78; 95% CI, 0.61 to 0.92; P < 0.01), and metronidazole resistance was nonlinear. Age was an independent predictor of resistance to all antibiotics. Time elapsed predicted resistance for clarithromycin and levofloxacin and dual resistance for clarithromycin-metronidazole. Secondary resistance of H. pylori to clarithromycin and metronidazole remains high. The low secondary resistance to levofloxacin makes it an attractive treatment option in our region for patients following two failed eradication attempts.

Background: The relationship between Helicobacter pylori 1 infection and coronary artery disease (CAD) has as yet not been fully examined. The myocardial perfusion imaging (MPI) stress test has proven its efficacy as an integral part of diagnosing CAD.Objectives: To investigate the association between CAD and H. pylori infection using MPI.Methods: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies: The CAD positivity group included patients with ischemia and/or myocardial infarction (MA) on a stress MPI, coronary artery bypass graft surgery (CABG), or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients' demographic data, risk factors for CAD, and childhood socioeconomic status were recorded.Results: The study group consisted of 300 consecutive patients, 170,men and 130:women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P= 0.005). In the adjusted analysis, H. pylori, infection was found to be associated with CAD positivity (odds ratio 1.83, 95% confidence interval 1.06-3.17, P= 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95%CI 1.44-7.84, P = 0.005). No association was noted with CagA positivity.Conclusions: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors.

We aimed to assess differences in bacterial intensities of Bacteroidetes phylum and different clostridial species in the human intestines with respect to C. difficile infection. Patients with a stool assay for C. difficile toxin were identified via the microbiology laboratory in our institute. Bacterial populations were quantified from stool samples of four groups of patients: Group I-patients with C. difficile associated diarrhea (CDAD); Group II-asymptomatic C. difficile carriers; Group III-patients with non-C. difficile diarrhea; Group IV-patients with no diarrhea and negative stool samples for the C. difficile toxin (control group). Stool was examined for three genes-C. difficile toxin A gene, 16S rRNA gene from Clostridium thermocellum representing other clostridial species, and 16S rRNA gene from Bacteroides fragilis representing the Bacteroidetes phylum. Fifty-nine patients underwent analysis of the stool (CDAD group 14, carriers group 14, non-C. difficile diarrhea group 16, control group 15). C. difficile concentration was highest in the CDAD group, followed by the carriers group. Higher concentrations of both clostridial species and Bacteriodetes were observed in the control and non-C. difficile diarrhea groups compared to the CDAD and carriers groups. We demonstrated an inverse association between infection with C. difficile and the abundance of Bacteroidetes phylum and other clostridial species in human intestines. Studies with larger samples and broader diagnostic procedures are needed in order to better explore and understand this association.

Structural heart disease, intravascular catheters, and invasive procedures are predisposing factors for infective endocarditis (IE). Data on IE in children with structurally normal hearts and no predisposing factors are limited. We aim to characterize IE (definite or possible by Duke criteria) in such a subgroup of pediatric patients (age <18 years) who were treated at our medical center. Of 51 events of IE in 50 children, 9 (18 %) had no predisposing factors. These infections were all community-acquired and presented with fever, a newly detected heart murmur, diagnostic echocardiographic findings, and left-sided infection. Clinical course was characterized by acute onset (n = 8 of 9) with a 100 % complication rate (heart failure or embolic phenomena). Emergency cardiac surgery was performed in 7 children (Ross surgery [n = 4], mitral valve replacement [MVR; n = 2], and valve repair [n = 1]). Causative organisms were S. aureus (n = 3), S. pneumoniae (n = 2), H. parainfluenzae (n = 1), and K. kingae (n = 1). In contrast, IE in children with predisposing factors (42 of 51 [82 %]) was frequently health care-associated (30 of 42), right-sided (20 of 42, p = 0.041), and with lower rates of diagnostic echocardiographic findings (28 of 42, p = 0.041), complications (16 of 42, p < 0.001), and surgical intervention (9 of 42, p = 0.002). Causative organisms were mainly viridans streptococci (n = 9), Candida species (n = 8), coagulase-negative staphylococci (n = 6), enteric Gram-negative bacilli (n = 6), S. aureus (n = 5), and K. kingae (n = 3). Mortality was 11 % in both groups. We conclude that pediatric IE in children with and without predisposing factors differs significantly. Due to the acute and complicated course of the latter, high awareness among pediatricians and prompt diagnosis are crucial.

BACKGROUND Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease and hospitalization in infants and young children. Infants of multiple births, who are often premature, might be more susceptible to developing a more severe RSV infection than singletons. OBJECTIVE To assess the impact of multiple births on the severity of RSV infection and define risk factors for acquiring RSV infection in infants of multiple birth. METHODS Clinical data on infants hospitalized with RSV infection between 2008 and 2010 were retrospectively collected. RESULTS Twins comprised 7.6% (66/875) of hospitalized infants with RSV bronchiolitis during the study period. Infants in the twin group were younger (122.4 +/- 131.7 vs. 204.5 +/- 278.8 days, P = 0.014), had a lower mean gestational age (35.3 +/- 2.6 vs. 38.6 +/- 2.5 weeks, P < 0.001), and were more likely to have been born prematurely compared with singleton infants (65.6% vs. 13%, P < 0.001). On a multivariable logistic regression analysis, young age, early gestational age and male gender were the only variables identified as risk factors for pediatric intensive care unit admission (P < 0.001, P < 0.001 and P = 0.03, respectively). In contrast, the mere fact of a child being a twin was not found to be a significant risk factor for disease severity. In addition, if one twin is hospitalized due to RSV infection, the other has a 34% chance of also being hospitalized with bronchiolitis. Young age was a significant risk factor for hospitalization of the second twin (P < 0.001) CONCLUSIONS: Our findings suggest that twins hospitalized with RSV bronchiolitis do not have an increased risk for severe infection as compared to singletons. However, a twin of an infant hospitalized with RSV infection has a considerable risk of also being hospitalized with bronchiolitis, thus close monitoring is recommended.

Objective: To analyze clinical features and outcomes of patients with hospital-acquired (HA) and healthcare-associated (HCA) Staphylococcus aureus bacteremia.Methods: A retrospective cohort study was conducted from 1988 to 2007. We compared patients with clinically significant HA with those with HCA S. aureus bacteremia. Risk factors for 30-day all-cause mortality were assessed using multivariable logistic regression analysis. Cox regression analysis was used to estimate the hazard ratio (HR) for 5-year mortality with 95% confidence intervals (CI).Results: Of 1261 episodes, 735 (58.3%) were HA and 526 (41.7%) were HCA. The percentage of MRSA was 48.2% (354/735) in HA vs. 42.2% (222/526) in HCA bacteremia; p = 0.04. The percentages of HCA S. aureus bacteremia and MRSA bacteremia did not vary throughout the study period. Mortality at 30 days was 40.2% (507/1261) and at 1 year was 63.4% (800/1261); this was comparable for HA and HCA bacteremia. Five-year survival curves in both settings followed very similar patterns (HR 1.01, 95% CI 0.89-1.15). Risk factors for 30-day mortality were similar, except for primary bacteremia and pre-existing heart valve disease in the HA group.Conclusions: HCA S. aureus bacteremia shares many similarities with HA bacteremia with respect to the prevalence of MRSA strains, mortality rates, and risk factors for death, and should be managed similarly. (C) 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

BACKGROUND:Cryptosporidium parvum is a common cause of diarrhea. In immunocompetent individuals, spontaneous recovery is the rule. In immunocompromised patients, it may cause a serious disease. Data on cryptosporidiosis in children after solid organ transplantation are few. We report on 6 pediatric solid organ recipients with gastroenteritis caused by Cryptosporidium. PATIENTS AND METHODS:All episodes of gastroenteritis in solid organ transplant recipients hospitalized in Schneider Children's Medical Center from January 2008 to August 2011 were identified. Data on the episodes with positive staining for Cryptosporidium antigen in stool were reviewed. RESULTS:Fifty-seven episodes of gastroenteritis were recorded. In 6 (11%) patients (4 kidney recipient, 1 liver and kidney recipient and 1 heart transplant recipient) Cryptosporidium antigen was detected in stool. Mean age at transplantation was 3.7 ± 2 years, mean time between transplantation and cryptosporidial disease was 39 ± 53.9 months. Symptoms included prolonged diarrhea, fever, abdominal pain and weight loss. Mean duration of symptoms before diagnosis was 10.5 ± 8.7 days. In 5 children, kidney function deteriorated, blood concentrations of tacrolimus increased in 5 patients and abnormal values of liver enzymes were detected in 4 patients. All patients were hospitalized and received intravenous fluid replacement and were treated with nitazoxanide for 5-21 days. Two patients had recurrence of symptoms after short course (5 days) therapy. All patients recovered eventually from the disease. CONCLUSION:Cryptosporidium should be routinely tested in solid organ transplant recipients with diarrhea. Delay in initiation of treatment can result in serious complications including acute renal failure. Long-term therapy with nitazoxanide (at least 14 days) may facilitate recovery.

ABSTRACT Monomicrobial necrotizing fasciitis (type II) is typically caused by group A streptococcus alone or in combination with Staphylococcus aureus. Escherichia coli has been isolated from polymicrobial or Fournier's gangrene but has rarely been reported in monomicrobial necrotizing fasciitis. We describe the clinical characteristics and outcomes of seven cases of monomicrobial E. coli necrotizing fasciitis and/or severe soft tissue infection diagnosed at a single institution during an 18-month period. Four isolates from three patients and two isolates from two patients with type I polymicrobial severe soft tissue infection (controls) were assayed by the randomly amplified polymorphic DNA (RAPD) analysis for fingerprinting and PCR amplification of primers in order to detect cytotoxic necrotizing factor 1 and 2 ( cnf1 and cnf2 ) genes. All patients had some type of immune suppression. The limb was the most commonly involved organ. In all cases, E. coli was isolated as a monomicrobial pathogen from blood, fascia, or both. All patients died during hospitalization, three within the first 48 h. The RAPD amplification assay showed a high degree of genetic diversity among the “flesh-eating” strains and controls. The cnf1 toxin gene was identified in two out of three cases, but not in the controls. cnf2 was not detected in any of the patients. E. coli may be responsible for life-threatening necrotizing fasciitis. Further research is needed to reveal relevant risk factors, reservoirs, and modes of transmission of cnf1 E. coli .

The objectives of this study were to characterize community-acquired (CA) enterococcal urinary tract infections (UTIs) in a tertiary pediatric center and to determine risk factors for their occurrence, their association with renal abnormalities, their antibiotic susceptibility profile, and the appropriateness of the empiric antibiotic treatment, in comparison to those of Gram-negative UTIs. In a 5-year prospective clinical and laboratory study, we found that enterococcal UTIs caused 6.2% (22/355) of culture-proven CA UTIs. Compared with Gram-negative UTI, enterococcal UTI was associated with male predominance, higher rates of underlying urinary abnormalities (70 vs. 43.7%; p = 0.03) and inappropriate empiric antibiotic therapy (22 vs. 5.6%; p = 0.02), and mainly vesicoureteral reflux (53% of cases). This study highlights the importance of early detection of CA enterococcal UTIs because of their association with underlying urinary abnormalities and a high rate of inappropriate empiric antibiotic therapy. Renal imaging is recommended for children with enterococcal UTIs; Gram stain is suggested in selected cases to detect Gram-positive cocci for early diagnosis of enterococcal UTIs and initiation of appropriate antibiotics.

Recently, 32% of Helicobacter pylori (H pylori) infected patients who were treated for differentiated thyroid carcinoma (DTC) were found to have a negative urease breath test at 2 months posttreatment. Our objectives were to eradication of clarify equivocal findings, and determine whether radioiodine eradicates this chronic bacterial infection. Twenty-eight patients (25 DTC patients and 3 with hyperthyroidism) positive for H pylori stool antigen were treated with oral radioiodine (131I) at a dose of 100 to 200 mCi in 18 patients with thyroid carcinoma; 30 mCi in 1 patient with a significant residual mass in the thyroid bed after surgery; and 4 mCi in 6 patients who had been treated with 100 to 150 mCi over the last 5 years. The hyperthyroid patients received 10 to 20 mCi. To standardize the results, and better compare with a previous study, only those patients who received a dose of 100 to 200 mCi were included for analysis. All 18 DTC patients who tested positive for H pylori stool antigen before radioiodine treatment remained positive 3 months posttreatment, indicating an eradication rate of 0% with an upper 95% confidence limit of 18.53%. Radioiodine administered to H pylori infected patients did not eradicate infection in Israeli patients. Recently, 32% of Helicobacter pylori (H pylori) infected patients who were treated for differentiated thyroid carcinoma (DTC) were found to have a negative urease breath test at 2 months posttreatment. Our objectives were to eradication of clarify equivocal findings, and determine whether radioiodine eradicates this chronic bacterial infection. Twenty-eight patients (25 DTC patients and 3 with hyperthyroidism) positive for H pylori stool antigen were treated with oral radioiodine (131I) at a dose of 100 to 200 mCi in 18 patients with thyroid carcinoma; 30 mCi in 1 patient with a significant residual mass in the thyroid bed after surgery; and 4 mCi in 6 patients who had been treated with 100 to 150 mCi over the last 5 years. The hyperthyroid patients received 10 to 20 mCi. To standardize the results, and better compare with a previous study, only those patients who received a dose of 100 to 200 mCi were included for analysis. All 18 DTC patients who tested positive for H pylori stool antigen before radioiodine treatment remained positive 3 months posttreatment, indicating an eradication rate of 0% with an upper 95% confidence limit of 18.53%. Radioiodine administered to H pylori infected patients did not eradicate infection in Israeli patients.

To characterize the clinical and laboratory manifestations of non-typhi Salmonella gastroenteritis associated with bacteremia in children less than 36 months old.

BACKGROUND:The rate of infection with Clostridium difficile colitis and its associated mortality have been increasing in the last decade. The molecular epidemiology of C. difficile in Israel has not been studied.OBJECTIVES:To screen for the existence of the 027 and 078 ribotypes and determine the longitudinal molecular epidemiology of the circulating clinical C. difficile isolates in a large hospital in central Israel.METHODS:Polymerase chain reaction (PCR) ribotyping was performed on C. difficile isolates obtained from hospitalized patients from November 2003 to May 2004 (first study period) and September 2009 (second study period). Isolates with PCR ribotype patterns, unlike those of the available reference strains (078 and 027), were labeled with letters. Forty-six isolates from the first study period and 20 from the second were analyzed.RESULTS:PCR strain typing of C. difficile isolates yielded approximately 26 unique ribotypes. During the first study period, ribotype A and B accounted for 30% and 28%, respectively, whereas ribotype E and K accounted for 6.5% for each. During the second study period, ribotypes A, E and K disappeared, and the incidence of ribotype B decreased from 28% to 15%. One isolate (1/20, 5%) emerged during the second period and was identified as ribotype 027. Moxifloxacin resistance was found in 93% of ribotype A isolates, 81% of the ribotype B group, and in 44% of other ribotypes.CONCLUSIONS:The predominant ribotypes circulating in our institution were diverse and changing. This is the first report on the emergence of the 027 ribotype in Israel.

BACKGROUNDStaphylococcus aureus infections are a major cause of morbidity and mortality worldwide. Clindamycin is widely used in the treatment of staphylococcal infections; however, it is our impression that in the last few years, inducible clindamycin resistance (ICR) has become more prevalent.OBJECTIVETo assess the prevalence of ICR in methicillin-sensitive Staphylococcus aureus (MSSA) infections among pediatric patients in Israel.METHODSWe reviewed the files of children diagnosed with MSSA infections during the period January 2006 to June 2007 forfull antibiogram (includingthe D-test for ICR), phage typing and randomly amplified polymorphic DNA.RESULTSAltogether, 240 MSSA isolates were recovered, mainly from wounds and abscesses. ICR was detected in 62 of 68 erythromycin-resistant/clindamycin-sensitive strains (91%); the ICR rate for the total number of isolates was 26% (62/240). Phage type analysis demonstrated that 38 of 61 ICR isolates (62%) were sensitive to group 2, compared to 42 of 172 isolates (24%) that did not express ICR (P < 0.01). On randomly amplified polymorphic DNA, phage type 2 isolates expressing ICR belonged to the same clone, which was different from ICR isolates sensitive to other phages and from isolates not expressing ICR.CONCLUSIONSInducible clindamycin resistance is common among methicillin-sensitive Staphylococcus aureus in Israeli children. The D-test should be performed routinely in all MSSA isolates.

The availability of a reliable and user-friendly method to identify pathogens causing sexually transmitted diseases (STDs) is essential to reduce the complications and spread of infection. In this study, genital/urinary specimens from 113 patients with STDs were simultaneously tested for 6 pathogens using the automated Seeplex® (Seegene, Seoul, Korea) multiplex polymerase chain reaction (PCR)-based STD6B auto-capillary electrophoresis (ACE) system. The results were compared with conventional reference methods, including culture and PCR tests. The sensitivity of STD6B ACE was found to be 100% for Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, Neisseria gonorrhoeae, and Trichomonas vaginalis, and 98% for genital Ureoplasma (U. urealyticum and U. parvum). Specificity ranged from 97% to 100%. One pathogen was detected in 51 specimens, and 2 or more pathogens were detected in 24. In conclusion, the multiplex PCR and ACE system is highly sensitive and specific for the rapid, simultaneous detection of STD pathogens directly from a single specimen.

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The miC50 and miC90 of the tested agents after 24 h of incubation were as follows: Tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC90). Overall, moxifloxacin was the most active agent in vitro against U. Urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.

Background: Community-associated methicillin-resistant Staphylococcus aureus infections are increasingly being documented worldwide. In Israel, however, CA-MRSA infections have not yet been reported, so awareness among physicians may be low.Objective: To alert physicians to the possibility of CA-MRSA infection, which necessitates a distinct therapeutic approachMethods: We present three children with soft tissue infections caused by CA-MRSA who were treated in our medical center from January to March 2009.Results: In all three cases CA-MRSA was identified as the causative pathogen after surgical or spontaneous drainage. On susceptibility testing, the organisms were resistant to beta-lactam antibiotics but susceptible to clindamycin, rifampicin and trimethoprim-sulfamethoxazole.Conclusions: Physicians should maintain an index of suspicion for CA-MRSA infections. The antibiotic-resistance profile of S. aureus should be watched carefully, and in particular, cultures should be obtained whenever soft tissue infections fail to respond to conventional treatment. IMAJ 2010, 12 428-430

OBJECTIVES:To determine the antibiotic susceptibility of Helicobacter pylori isolates from Israeli children; assess the role of previous antibiotic use in the development of antibiotic resistance and examine the possibility of simultaneous colonization of strains with different resistance patterns in the same patients. MATERIAL AND METHODS:A prospective case-series design was used. The study group included 174 patients aged 1-18 years referred to the Schneider Children's Medical Center of Israel for gastroscopy over a 2.5-year period. Antibiotic susceptibility to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin was determined by E-test on gastric biopsies (2 per patient). Clinical and demographic data were obtained by questionnaire. RESULTS:Cultures for H. pylori yielded 55 isolates from 53 children. In treatment-naïve children, the prevalence rate of primary resistance to clarithromycin was 25% and to metronidazole, 19%. Respective rates in children previously treated for H. pylori infection were 42% (p = 0.22) and 52% (p = 0.016). Simultaneous resistance to both drugs was found in 13% of isolates (n = 7), all from children with previous treatment failure. No resistance was found to amoxicillin, tetracycline or levofloxacin. Clarithromycin resistance was associated with macrolide use for any indication during the previous year (p = 0.033). In 2 patients (3.8%), a different H. pylori strain was cultured from each biopsy. CONCLUSIONS:H. pylori resistance to clarithromycin and metronidazole is high in Israeli children, particularly in those previously treated for H. pylori infection, in whom culture-based treatment should be considered. The simultaneous colonization of multiple strains in a minority of patients needs to be further characterized.