Israel Medical Association Journal

Background: Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates.

Objectives: To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance.

Methods: In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen.

Results: No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin.

Conclusion: The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.

Background: Antibiotic stewardship programs are necessary to test the appropriateness of local guidelines for empirical antibiotic treatment by audits.

Objectives: To assess whether compliance to local guidelines achieved a higher rate of appropriate antibiotic treatment and reduced morbidity and mortality, and whether infectious disease counseling improved the rate of appropriate treatment.

Methods: Our cohort comprised 294 patients with proven bacteremia. Data were retrieved from medical records including diagnosis, empiric antibiotic treatment, and outcomes.

Results: The empirical treatment was consistent with bacterial susceptibility in 227 patients (77%), and matched in 64% of the time to the first line, and another 24% to the second line of institutional guidelines. A strong correlation was found between appropriate empiric treatment according to bacterial susceptibility and reduced mortality (odds ratio [OR] 0.403, P = 0.007). A similar correlation was found with the choice of appropriate antibiotics according to local guidelines (OR 0.392, P = 0.005). Infectious disease consultation was related to an increase in the rate of appropriateness of treatment according to guidelines (85% vs.76%, P = 0.005). A tendency to increased appropriateness was related to microbial susceptibility (87% vs. 74%, P = 0.07).

Conclusions: In this study, initiation of appropriate empiric antibiotic therapy, according to the hospital's guidelines, was found associated with reduced mortality in patients with bacteremia.

Background: Urinary tract infection (UTI) is a common bacterial infection in children.

Early treatment may prevent renal damage in pyelonephritis. The choice of empiric antibiotic treatment is based on knowledge of the local susceptibility of urinary bacteria to antibiotics. In Israel the recommended empiric oral antibiotic treatment are First or second generation cephalosporin, trimethoprim-sulfamethoxazole or amoxicillin-clavulanic acid.

Objectives: To describe resistance rates of urine bacteria isolated from children with UTI in the community settings. Identify risk factors for resistance.

Methods: A retrospective cross-sectional study of UTI in children aged 3 months to 18 years diagnosed with UTI and treated as outpatients in a large community clinic between 7/2015 and 7/2017 with a diagnosis of UTI.

Results: A total of 989 urinary samples were isolated, 232 were included in the study. Resistance rates to cephalexin, cefuroxime, ampicillin/clavulanate and Trimethoprim-Sulfamethoxazole were 9.9%, 9.1%, 20.7%, and 16.5%, respectively. Urinary tract abnormalities and recurrent UTI were associated with an increase in antibiotic resistance rates. Other factors such as age, fever, and previous antibiotic treatment were not associated with resistance differences.

Conclusions: Resistance rates to common oral antibiotics were low compared to previous studies performed in Israel in hospital settings. First generation cephalosporins are the preferred empiric antibiotics for febrile UTI for outpatient children. Amoxicillin/clavulanate is not favorable due to resistance of over 20% and the broad spectrum of this antibiotic. Care should be taken in children with renal abnormalities as there is a worrying degree of resistance rates to the oral first line antibiotic therapy.

Background: Extended-spectrum beta-lactamase (ESBL) production is the most common antimicrobial resistance mechanism in the neonatal intensive care unit (NICU), with colonization and blood stream infections being a major threat to this population. Since 2013, all NICU admissions at our facility were screened twice weekly for ESBL colonization.

Objectives: To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU.

Methods: A retrospective case study of ESBL-colonized infants vs. controls (matched by date of birth and gestational age) was conducted in the NICU of Soroka University Medical Center, Israel, between 2013 and 2014. Epidemiological, laboratory, and clinical data were extracted from medical files. Univariable and multivariable analyses were used to assess associations between ESBL colonization and possible clinical risk factors.

Results: Of 639 admissions during the study period, 87 were found to be ESBL-colonized (case infants) and were matched to 87 controls. Five case infants became infected (5.7%) with ESBL strains. Klebsiella pneumoniae was the most common isolated bacteria. The mean time from admission to colonization was 15 days. Univariable analysis showed an association of male gender and highest Apgar score at 1 and 5 minutes with ESBL colonization (P < 0.05). Multivariable analysis yielded only a possible association of higher Apgar score at 1 and 5 minutes (hazard ratio [HR] 1.515, 95% confidence interval [95%CI] 0.993-2.314; HR 1.603, 95%CI 0.958–2.682, respectively) with ESBL colonization.

Conclusions: Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Background: Little is known about the incidence of urinary tract infections (UTI) in the dispersed Bedouin population. UTIs are routinely treated empirically according to local resistance patterns, which is important when evaluating the risk factors and antibiotic resistance patterns in the Bedouin population.

Objectives: To analyze risk factors, pathogens, and antibiotic resistance patterns of UTIs in the Bedouin population compared to the general population in southern Israel. To compare data from this study to that from a previous study conducted at our center.

Methods: We prospectively followed all patients hospitalized with community acquired UTIs during a 4 month period at Soroka Medical Center. We also compared results from this study to those from a study conducted in 2000.

Results: The study comprised 223 patients: 44 Bedouin (19.7%), 179 (80.3) non-Bedouin; 158 female (70.9%), 65 male (29.1). The Bedouin were younger (51.7 vs. 71.1 years of age, P < 0.001) and had a lower Charlson Comorbidity Index (2.25 vs. 4.87, P < 0.001). Enterobacteriaceae were the most common pathogens identified, and Escherichia coli (E. coli) was the most common with 156 (70%) strains identified, followed by Klebsiella spp. with 29 (13%), Proteus spp. with 18 (8%), pseudomonas with 9 (4%), and other bacteria including enterococci with 11 (5%). The prevalence of E. coli increased significantly from 56% in 2000 to 70% in this study. We also noted an increase in community acquired extended spectrum beta lactamase (ESBL) pathogens from 4.5% in 2000 to 25.5% in the present study. No statistically significant difference was observed between the Bedouin and general populations in the causal pathogens, resistance to antibiotics, length of therapy, and readmission rate within 60 days. 

Conclusions: The Bedouin population hospitalized for UTIs is younger and presents with fewer co-morbidities. Isolated pathogens were similar to those found in the general population as was the presence of drug resistant infections. Overall, a substantial percentage of pathogens were resistant to standard first-line antibiotics, driving the need to change from empiric therapy to aminoglycoside therapy. 

 

Background: Although the presence of bacteria in the cervix is not a sign of disease, the majority of pathogens involved in pelvic inflammatory disease originate from this "normal" flora.

Objectives: To assess the distribution of cervical non-gonococcal and non-chlamydial bacteria in hospitalized women with PID[1] and the bacteria's antibiotic sensitivity.

Methods: We retrospectively evaluated the cultures obtained from the uterine cervix over a 1 year period (2008) at Wolfson Medical Center, Holon. The distribution of cervical non-gonococcal and non-chlamydial bacteria in women with PID and the bacteria's antibiotic sensitivity was compared to that in our previous 1 year study that was performed at Kaplan Medical Center, Rehovot (1988–89). 

Results: In 2008, a total of 412 cultures were obtained of which 126 (30.5%) were sterile. The prevalence of negative cultures was similar in 2008 and in 1988, namely, 30.5% and 33.7%, respectively (P = 0.23). PID was finally diagnosed in 116 patients with positive cultures. The most prevalent bacteria in the 2008 study were Enterococcus species and Escherichia coli – 24.0 % and 26.4% respectively compared to 18.0% and 38.1% in the 1988 study, with the decrease in E. coli isolates being significant (P = 0.0003). In 2008 the antimicrobial sensitivity for various antibiotics ranged from 44.3% to 100.0% (median 90.2%) while in 1988 it ranged from 2.9% to 80.1% (median 51.9%).

Conclusions: The cervical bacterial flora in hospitalized women with PID did not vary significantly between 1988 and 2008. However, antimicrobial sensitivity of the isolated bacteria increased dramatically, probably due to a decrease in resistance to antibiotics.

Background: Identification of pathogens and their susceptibility to antimicrobials is mandatory for successful empiric antibiotic treatment.

Objectives: To compare the clinical characteristics of patients with bacteremia, as well as the bacterial distribution and antimicrobial susceptibility in community, hospital and long-term care facilities during two periods (2001–2002 and 2005–2006).

Methods: The study was conducted at the HaEmek Medical Center, a community 500-bed teaching hospital in northern Israel serving a population of ~500,000 inhabitants. All episodes of bacteremia (n=1546) during two 2 year periods (2001–2 and 2005–6) were prospectively recorded, evaluated and compared (755 in 2001–2 and 791 in 2005–6).

Results: In both periods the urinary tract was the main port of entry in community and long-term care facility bacteremia, while the urinary tract – primary and catheter-related – were similar in frequency as sources of hospital bacteremia. Escherichia coli was the most frequent pathogen isolate. No significant changes in the frequency of methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing bacteria were seen between the two 2 year periods (2001–2 and 2005–6). The susceptibility of non-ESBL[1]-producing E. coli decreased for some antibiotics while non-ESBL-producing Klebsiella pneumoniae susceptibility profile improved in the same period. A non-statistically significant trend of increased resistance in gram-negative isolates to quinolones, piperacillin and piperacillin-tazobactam was observed, but most isolates still remained highly susceptible to carbapenems. There was a small increase in mortality rate in hospital bacteremia during the second period.

Conclusions: Continuous surveillance is imperative for monitoring the local epidemiology and for developing local treatment guidelines.

Background: According to the U.S. Centers for Disease Control guidelines, prolonged rupture of membranes mandates intrapartum antimicrobial prophylaxis for group B Streptococcus whenever maternal GBS[1] status is unknown.

Objectives: To evaluate the local incidence, early detection and outcome of early-onset GBS sepsis in 35–42 week old neonates born after PROM[2] to women with unknown GBS status who were not given intrapartum antimicrobial prophylaxis.

Methods: During a 1 year period, we studied all neonates born beyond 35 weeks gestation with maternal PROM ≥ 18 hours, unknown maternal GBS status and without prior administration of IAP[3]. Complete blood count, C-reactive protein, blood culture and polymerase chain reaction amplification of bacterial 16S rRNA gene were performed in blood samples collected immediately after birth. Unfavorable outcome was defined by one or more of the following: GBS bacteremia, clinical signs of sepsis, or positive PCR[4].

Results:  Of the 3616 liveborns 212 (5.9%) met the inclusion criteria. Only 12 (5.7%) of these neonates presented signs suggestive of sepsis. PCR was negative in all cases. Fifty-eight neonates (27.4%) had CRP[5] > 1.0 mg/dl and/or complete blood count abnormalities, but these were not significantly associated with unfavorable outcome. Early-onset GBS sepsis occurred in one neonate in this high risk group (1/212 = 0.47%, 95% CI 0.012–2.6). 

Conclusions: In this single-institution study, the incidence of early-onset GBS sepsis in neonates born after PROM of ≥ 18 hours, unknown maternal GBS status and no intrapartum antimicrobial prophylaxis was 0.47%.

Background: In an era of increasing antimicrobial resistance, knowledge of local antimicrobial susceptibility patterns of common uropathogens is essential for prudent empiric therapy of community-acquired urinary tract infections.

Objectives: To define antimicrobial susceptibility of Gram-negative uropathogens in northern Israel over a 10 year period and to compare it with antibiotic-use patterns in the same community.

Methods: We tested the susceptibility of all Gram-negative urinary isolates from outpatients at HaEmek Medical Center over the years 1995, 1999, 2002 and 2005 to common antimicrobial agents. MIC₉₀ of Escherichia coli to some of these agents was determined and antibiotic consumption data over the years 2000–2005 (DDD/1000/day) were obtained.

Results: We observed a rise in susceptibility rates of E. coli to amoxicillin-clavulanate, trimethoprim-sulfamethoxazole and nitrofurantoin and of other Gram-negative isolates to amoxicillin-clavulanate, ceftriaxone and cephalothin. Susceptibility rates of all Gram-negative uropathogens to ciprofloxacin decreased significantly. MIC₉₀ of E. coli for all drugs tested remained stable. There was a significant decrease in the use nitrofurantoin and TMP-SMX[1] and a significant increase in the use of ampicillin, cephalothin and ceftriaxone.

Conclusions: Antibiotic resistance patterns mostly remained unchanged or improved slightly. There was, however, a constant decrease in susceptibility of all Gram-negative uropathogens to ciprofloxacin. Antibiotic use patterns could not explain the changes seen in antibiotic susceptibility patterns.

Background: The association between antibiotic use in the community and antimicrobial resistance is known. Attention has recently focused on the type of agents being prescribed.

Objectives: To implement, evaluate and compare the efficacy of two community interventions programs – continuous versus seasonal medical education – oriented to primary care physicians with emphasis on appropriate use of antimicrobial drugs.

Methods: From October 2000 to April 2003 we conducted two interventions: a) a monthly educational campaign in selected clinics promoting appropriate diagnosis of common infectious diseases and prudent antibiotic use (continuous intervention group); and b) a massive educational campaign, conducted before two consecutive winters, promoting the judicious use of antibiotics for treating respiratory infections (continuous intervention group and seasonal intervention group). Sixteen similar clinics were randomized (8 to each group). The total antibiotic use was measured as defined daily dose/1000 patients/day, and compared between the groups. 

Results: The total use of antibiotics decreased between 1999-2000 and 2002-2003 in both groups, but slightly more significantly in the continuous intervention group. The DDD/1000 patients/day for the seasonal group in 1999-2000 was 27.8 vs. 23.2 in 2002-2003; and for the continuous group 28.7 in 1999-2000 vs. 22.9 in 2002-2003, a reduction of 16.5% and 20.0% respectively (p<0.0001). The main change in antibiotic use was noted for broad-spectrum antibiotics.

Conclusions: We present a successful community intervention program aimed to reduce unnecessary antibiotic use. Amplification of this type of intervention is imperative to stop the increase in antimicrobial resistance.