Israel Medical Association Journal

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-positive group included patients with ischemia and/or myocardial infarctions (MI) 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- positive (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. 

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. 

Objectives: To evaluate the performance of the C. DIFF QUIK CHEK COMPLETE^® assay, designed to simultaneously detect C. difficile-produced glutamate dehydrogenase (GHD) and toxins A and B.

Methods: Using the C. DIFF QUIK CHEK COMPLETE assay, the Tox A/B EIA, and polymerase chain reaction (PCR), we tested 223 stool specimens from hospitalized patients with antibiotics-associated diarrhea. Sensitivity and specificity, and positive and negative predictive values (PPV, NPV) were calculated for the C. DIFF QUIK CHEK COMPLETE test and the Tox A/B EIA against PCR

Results: The C. DIFF QUIK CHEK COMPLETE test had a sensitivity of 83.5% and specificity of 94.3% compared to PCR for Tox A/B, with 93.7% correlation (PPV 98.5%, NPV 91.7%). The Tox A/B EIA yielded corresponding values of 72.1% and 93.1%, with 85.6% correlation (PPV 85.1%, NPV 85.8%).

Conclusions: Given the importance of an early and appropriate diagnosis of Clostridium difficile-associated infection, the C. DIFF QUIK CHEK COMPLETE test may be of huge benefit to practitioners.

Background: Staphylococcus aureus infection is 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.

Objective: To assess the prevalence of ICR[1] in methicillin-sensitive Staphylococcus aureus (MSSA) infections among pediatric patients in Israel.

Methods: We reviewed the files of children diagnosed with MSSA[2] infections during the period January 2006 to June 2007 for full antibiogram (including the D-test for ICR), phage typing and randomly amplified polymorphic DNA.

Results: Altogether, 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.

Conclusions: Inducible clindamycin resistance is common among methicillin-sensitive Staphylococcus aureus in Israeli children. The D-test should be performed routinely in all isolates of MSSA.

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 as yet 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[1] 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.

Background: Streptococcus pneumoniae is now the predominant pathogen causing meningitis. The resistance of S. pneumoniae to penicillin and third-generation cephalosporins has grown steadily.

Objectives: To assess the antibiotic susceptibility of S. pneumoniae isolated from the cerebrospinal fluid of children with meningitis, and determine the antibiotic regimen appropriate for suspected bacterial meningitis in Israel.

Methods:  The study group included 31 children with 35 episodes of meningitis hospitalized from 1998 to 2006. S. pneumoniae isolates from the cerebrospinal fluid were tested for susceptibility to penicillin and ceftriaxone.

Results: Of the 35 isolates, 17 (48.6%) showed resistance to penicillin (minimum inhibitory concentration ≥ 0.12 µg/ml). Only 3 isolates (8.6%) showed intermediate resistance to ceftriaxone (≥ 0.5 and < 2 μg/ml), and none showed complete resistance (MIC[1] ≥ 2 μg/ml). The rates of antibiotic resistance were higher in children who were treated with antibiotics prior to admission (penicillin 88.9% vs. 34.6%, P = 0.007; ceftriaxone 22.2% vs. 3.8%, P = 0.156).

Conclusions:  The rate of penicillin resistance is high in children with S. pneumoniae meningitis in Israel, especially in those treated with oral antibiotics prior to admission. Resistance to ceftriaxone is infrequent though not negligible. On the basis of these findings, current recommendations to empirically treat all children with suspected bacterial meningitis with ceftriaxone in addition to vancomycin until the bacterial susceptibility results become available are justified also in Israel.

Background: The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia.

Objectives: To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel.

Methods: We conducted a prospective data collection on all patients with neutropenia (< 500/mm³) and clinically significant bacteremia or fungemia during the period 1988–2004.

Results: Among adults (462 episodes) the most common bloodstream isolate was Esherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3 throughout the study period. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital.
Conclusions: Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients’ risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment

Objectives: To determine whether there is an association between the presence and severity of adult calcific aortic stenosis and Chlamydia pneumoniae seropositivity

Methods: Forty adult patients (23 women, 17 men) were divided into three groups according to echocardiographic aortic valve area: Group A – 7 symptomatic subjects (age 67 ± 7 years) with normal aortic valve and normal coronary angiogram, Group B – 16 patients (age 73 ± 6) with moderate ACAS[1] (AVA[2]> 0.8 £ 1.5 cm²), and Group C – 17 patients (age 76 ± 7) with severe ACAS (AVA £ 0.8 cm²). We tested for immunoglobulins M, G and A as retrospective evidence of C. pneumoniae infection using the micro-immunofluorescence method. Past C. pneumoniae infection was defined by IgG titer > 16 £ 512.

Results: No patients in Group A showed positive Ig[3] for C. pneumoniae. IgM was not detected in any of the patients with ACAS (groups B and C) while 2 of 17 patients (12%) in group C showed IgA for the pathogen. High titers of IgG were found in 14 of 33 (42%) of the patients with moderate or severe ACAS: 5 of 16 (31%) in group B and 9 of 17 (53%) in group C (P = 0.2). Both groups had the same prevalence of coronary artery disease (66%). AVA was lower in IgG-seropositive patients than in the seronegative group (0.88 ± 0.3 cm² vs. 1.22 ± 0.4 cm², respectively, P = 0.02).

Conclusions: Past C. pneumoniae infection may be associated with a higher prevalence and greater severity of ACAS.

Objectives: To test the in vitro activity of linezolid (oxazolidinone) and other antimicrobial agents against MRSA[1] isolates recovered from hospitalized patients.

Methods: We tested 150 MRSA isolates recovered from hospitalized patients. The minimal inhibitory concentration of vancomycin, teicoplanin, pristinamycin (quinupristin-dalforistin), and linezolid was determined by the Etest method. Susceptibility to other antibiotics was tested by the disk diffusion method.

Results: All isolates were sensitive to vancomycin, teicoplanin, pristinamycin, and linezolid. The MIC₉₀ was 2.0 mg/ml for vancomycin and teicoplanin (range 0.5–2.0 mg/ml and 0.125–2.0 mg/ml, respectively), and 0.5 mg/ml for pristinamycin and linezolid (range 0.125–0.75 mg/ml and 0.125–0.5 mg/m, respectively). Of the other antibiotics, fusidic acid showed the best in vitro activity, with 96.7% susceptibility, associated with trimethoprim/sulfamethoxazole (85.8%) and minocycline (84%). Penicillin was associated with the lowest susceptibility (1.3%), associated with ofloxacin (3%) and erythromycin (14%). An increase in the minimal inhibitory concentration value of vancomycin was associated with a significant decrease in resistance to TMP-SMZ[2] (P < 0.01) and an apparent increase in resistance to other antibiotics.

Conclusion: The excellent in vitro activity of linezolid and its reported in vivo effectiveness renders it an important therapeutic alternative to vancomycin in the treatment of MRSA infection.

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[1] MRSA = methicillin-resistant Staphylococcus aureus

[2] TMP-SMX = trimethoprim/sulfamethoxazole

Background: Vaginal symptoms are a leading reason for a patient to visit her gynecologist. Little is known about the prevalence of the different causes of vaginitis and the risk factors for this entity in Israel.

Objective: To determine the prevalence in a gynecologic practice in Israel of the main forms of vaginitis: vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis.

Methods: We evaluated 208 patients presenting with vaginal symptoms to a gynecologic clinic; 100 asymptomatic women who attended the clinic for routine check-up served as controls. Demographic, medical and gynecologic histories were obtained, and a pelvic examination was performed in all patients. Vaginal specimens were tested for pH and amine reaction, smeared for Gram-staining and cultured for yeasts and Trichomonas vaginalis. Bacterial vaginitis was diagnosed using the Nugent scoring system. candida infection was diagnosed by microscopic examination and by culture.

Results: Candida spp. was the most common pathogen, documented by microscopy and culture in 35.5% of symptomatic women and 15% of asymptomatic controls (P < 0.001). Detection by culture only (negative microscopy) was documented in 18.7% of symptomatic patients and 15% of controls (P = 0.5). Bacterial vaginosis (Nugent score ≥ 7) was diagnosed in 23.5% of patients and 13% of controls (P = 0.04). Trichomoniasis was present in 8.1% of symptomatic women and 4% of controls (P = 0.1). The main risk factors were antibiotic use for candidiasis and lack of use of oral contraception and condom use for trichomoniasis.

Conclusion: Candida was by far the most common pathogen detected in our population. A statistically significant difference between patients and controls was noted for the prevalence of microscopically diagnosed candidiasis and bacterial vaginosis.