Spinal epidural abscess: in search of reasons for an increased incidence.

BACKGROUND: Spinal epidural abscess (SEA) is a rare disease with a potentially devastating outcome, and a reported incidence traditionally estimated at 0.2-2 cases/10,000 hospital admissions. Since the implementation in October 2007 of a program to increase medical personnel's awareness of SEA, we have documented a sharp increase in the incidence of SEA at our medical center OBJECTIVES: To investigate the cause of the increased incidence of SEA. METHODS: All cases diagnosed with SEA during the period 1998-2010 were retrospectively reviewed. Cases diagnosed before 2007 were compared with those diagnosed thereafter. RESULTS: From January 1998 to October 2007 SEA was diagnosed in 22 patients (group A), giving an annual incidence of 0.14-0.6 cases per 10,000 admissions. During the period November 2007 to April 2010, 26 additional patients were diagnosed (group B), yielding an incidence of 0.81-1.7 cases per 10,000 admissions (P < 0.01). The two groups did not differ significantly in epidemiological, clinical or laboratory characteristics, or in the causative bacteria isolated. CONCLUSIONS: The threefold rise in the incidence of SEA observed at a tertiary medical center in Tel Aviv since November 2007 was not explained by different host characteristics or by more virulent bacterial isolates. We suggest that heightened awareness of the clinical presentation and timely utilization of MR imaging has resulted in more cases being identified.

Evaluating real-life clinical and economical burden of amphotericin-B deoxycholate adverse reactions.

BACKGROUND: Amphotericin-B (AMB) is associated with toxicity such as renal impairment, hypokalemia and infusion-related events (IRE). With the advent of AMB lipid formulations and newer antifungal drugs, presenting improved safety profiles, it was suggested that using the conventional deoxycholate (AMB-D) formulation should no longer be regarded acceptable. OBJECTIVES: Evaluation of real-life incidence of AMB-D-related adverse-drug effects (ADE) and associated costs. SETTING: Hadassah Hebrew University Medical Center, Jerusalem, Israel, a tertiary 1,100-bed teaching hospital. METHODS: A 1-year single-center prospective observational study following all patients administered AMB-D. Various parameters related to AMB-D administration were recorded. Main outcome measures Subsequent ADE-related events, discontinuations, switch to alternative antifungals and related resource-utilization were monitored. RESULTS: Among 119 patients (60 children, 59 adults) receiving AMB-D, serum creatinine doubling from baseline, hypokalemia and IRE occurred in 14.3 % (15 % in children, 13.6 % in adults), 16.8 % (16.6 % in children, 16.9 % in adults) and 10.9 % (10 % in children, 11.8 % in adults), respectively. AMB-D was discontinued due to an ADE in 12.6 % of patients (6.7 % in children, 18.6 % in adults). The total annual cost associated with AMB-D use was 58,600. CONCLUSION: The clinical as well as economic burden of AMB-D associated ADE, as observed in real-life settings, appears to be manageable. Considering the significant cost implications associated, as suggested by simulated evaluation of an overall theoretic replacement of AMB-D by an equivalent volume of alternative antifungals, total abandonment of AMB-D appears unjustified.

Role of antibiotic therapy in mild acute calculus cholecystitis: a prospective randomized controlled trial.

BACKGROUND: Current recommendations for treating acute calculus cholecystitis include the use of intravenous antibiotics, although these recommendations were never tested scientifically. The aim of this study was to evaluate the role of intravenous antibiotic therapy in patients with mild acute calculus cholecystitis. METHODS: In this prospective, randomized controlled trial, 84 patients with a diagnosis of mild acute calculus cholecystitis were randomly assigned to supportive treatment only or supportive treatment with intravenous antibiotic treatment (42 patients in each arm). Patients were followed through their index admission and until delayed laparoscopic cholecystectomy was performed. RESULTS: The two study groups did not differ in their demographic data or in the clinical presentation and disease severity. Analysis was conducted on the intent-to-treat basis. Patients in the intravenous antibiotics arm resumed a liquid diet earlier (1.7 vs. 2.2 days, p = 0.02) but did not significantly differ in resumption of regular diet (2.8 vs. 3.2 days, p = 0.16) or hospital length of stay (LOS) (3.9 vs. 3.8 days, p = 0.89). Patients in the intravenous antibiotics arm had rates of percutaneous cholecystostomy tube placement (12 vs. 5 %, p = 0.43), readmissions (19 vs. 13 %, p = 0.73), and perioperative course similar to those not receiving antibiotics. The overall hospital LOS, including initial hospitalization and subsequent cholecystectomy, was similar for both groups (5.6 vs. 5.1 days, p = 0.29). Eight (19 %) patients in the supportive arm were crossed over to the intravenous antibiotic arm during the index admission. CONCLUSIONS: Intravenous antibiotic treatment does not improve the hospital course or early outcome in most of the patients with mild acute calculus cholecystitis.

Chemical trapping of vancomycin: a potential strategy for preventing selection of vancomycin-resistant Enterococci.

Emergence of antimicrobial resistance is among the most worrisome issues in public health worldwide. Vancomycin resistance is rapidly spreading, resulting in increased morbidity, mortality, and healthcare-associated costs. Multiple strategies are required to preserve the effectiveness of this essential antibiotic. It has been recently shown that biliary excretion of vancomycin following parenteral administration results in significant fecal concentrations of vancomycin that may lead to selection of vancomycin-resistant strains within the colon. In this study we present a novel strategy for preventing this undesired effect and its consequences, using chemical trapping of vancomycin by a tripeptide analog that mimics the natural bacterial vancomycin binding-site. Initially, we demonstrated that a tripeptide analog can neutralize vancomycin activity against Enterococci at a molar excess of 28. In the second phase, two chemical modifications, designed to attach the tripeptide to vancomycin covalently, were explored. Attachment of a 4-flurosulfonyl-benzoic acid (FSBA) moiety to the parent tripeptide resulted in vancomycin neutralization at a molar ratio of less than 4:1. Finally it was shown that the FSBA-bound tripeptide analog can prevent in-vitro selection of vancomycin-resistant Enterococci (VRE) from a mixed vancomycin susceptible/resistant population following exposure to vancomycin. These findings demonstrate the ability of the proposed strategy to prevent selection of VRE. The present proof-of-concept study provides the basis for further development of the proposed strategy. Further, this strategy may be implemented for combating resistance to other antimicrobials.

Increased extent of and risk factors for pandemic (H1N1) 2009 and seasonal influenza among children, Israel.

During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. Children hospitalized for pandemic (H1N1) 2009 were older and had more underlying chronic diseases than those hospitalized for seasonal influenza.

Labor as a bacteriuric event--assessment and risk factors.

OBJECTIVE: Little is known regarding the prevalence of early postpartum bacteriuria. We sought to evaluate the incidence of bacteriuria following labor and to identify risk factors predisposing to this condition. METHODS: Three hundred and fifty parturients were recruited, 301 were included in the analysis. Women receiving antibiotic drugs during delivery were excluded. Urine cultures were obtained from the study group before delivery and prior to discharge. Data regarding management of labor was collected prospectively. RESULTS: Positive urine cultures were present on admission in 5.4% of women, whereas 12.9% had a positive urine culture at discharge (p < 0.003). Bacteriuria was acquired during labor in 12.7% of patients who had negative cultures on admission. Escalating number of digital vaginal examinations (p = 0.04), recurrent bladder catheterization (p = 0.05), duration of epidural anesthesia (p = 0.002), and vacuum delivery (p = 0.02) correlated significantly with an increased risk for acquiring bacteriuria. CONCLUSION: Labor is a bacteriuric event. Iatrogenic interventions can predispose parturients with sterile urine cultures to postpartum bacteriuria.

Implications on emergence of antimicrobial resistance as a critical aspect in the design of oral sustained release delivery systems of antimicrobials.

PURPOSE: To assess the effects of the unabsorbed fraction of an orally administered antimicrobial drug which enters the colon on the emergence of resistance among the natural microflora, a phenomenon largely overlooked so far despite its clinical importance, especially when sustained release formulations are used. METHODS: Effects of an orally administered model beta-lactam antibiotic (amoxicillin) on emergence of resistant bacteria were assessed using a microbiological assay for qualitative and quantitative determination of resistant bacteria in fecal samples of rats following gastric administration of the drug to rats for 4 consecutive days. Time- and site-controlled administration of a beta-lactamase to the rat colon was assessed as a potential strategy for prevention the emergence of resistant bacteria following oral administration of incompletely absorbed antimicrobials. RESULTS: Emergence of resistant bacteria was demonstrated following oral administration of amoxicillin to rats, whereas de-activation of the beta-lactam prior to entering the colon, by infusion of a beta-lactamase into the lower ileum, was shown to prevent the emergence of resistant colonic bacteria. CONCLUSIONS: This study illustrates the need to consider the emergence of antimicrobial resistance as a goal equally important to microbiological and clinical cure, when designing oral sustained-release delivery systems of antimicrobial drugs.

Iontophoretic treatment of experimental pseudomonas keratitis in rabbit eyes using gentamicin-loaded hydrogels.

PURPOSE: To evaluate the efficacy of iontophoresis using a hydrogel probe containing gentamicin for the treatment of Pseudomonas keratitis in the rabbit cornea. METHODS: Five groups (Groups 1-5) of 8 rabbits each were infected by injecting Pseudomonas aeruginosa into their corneas. Three dosings of corneal iontophoresis were performed, at intervals of 3.5 hours, using soft disposable gentamicin-loaded hydroxyethyl methacrylate hydrogel discs mounted on a portable iontophoretic device. Groups 1 and 2 were treated with corneal iontophoresis for 60 seconds and a current of 0.5 and 0.2 mA. Groups 3 and 4 were treated with hydrogel loaded with 0.9% NaCl solution, using a current of 0.2 mA and mock iontophoresis. Group 5 was treated with eye drops of 1.4% gentamicin every hour for 8 hours. One and a half hours after the last treatment, the animals were killed, and the corneas were excised and cultured for P. aeruginosa count after 24-hour incubation. RESULTS: After iontophoretic treatment of gentamicin with a current of 0.5 mA (Group 1), the logarithmic value of Pseudomonas colony-forming units (CFUs) was 2.96 +/- 0.45. After lower current iontophoretic treatment (Group 2), the logarithmic Pseudomonas count was 5.25 +/- 0.54 CFUs. At the control groups (Groups 3-5), the Pseudomonas counts were found to be much higher, 7.62 +/- 0.28, 7.22 +/- 0.29, and 6.29 +/- 0.45 CFUs, respectively. CONCLUSION: A short iontophoretic treatment using gentamicin-loaded hydrogels has potential clinical value in treating corneal infections.

Empiric treatment of uncomplicated urinary tract infection with fluoroquinolones in older women in Israel: another lost treatment option?

BACKGROUND: Current guidelines for the treatment of uncomplicated urinary tract infection (UTI) in women recommend empiric therapy with antibiotics for which local resistance rates do not exceed 10-20%. We hypothesized that resistance rates of Escherichia coli to fluoroquinolones may have surpassed this level in older women in the Israeli community setting. OBJECTIVES: To identify age groups of women in which fluoroquinolones may no longer be appropriate for empiric treatment of UTI. METHODS: Resistance rates for ofloxacin were calculated for all cases of uncomplicated UTI diagnosed during the first 5 months of 2005 in a managed care organization (MCO) in Israel, in community-dwelling women aged 41-75 years. The women were without risk factors for fluoroquinolone resistance. Uncomplicated UTI was diagnosed with a urine culture positive for E. coli. The data set was stratified for age, using 5 year intervals, and stratum-specific resistance rates (% and 95% CI) were calculated. These data were analyzed to identify age groups in which resistance rates have surpassed 10%. RESULTS: The data from 1291 urine cultures were included. The crude resistance rate to ofloxacin was 8.7% (95% CI 7.4 to 10.2). Resistance was lowest among the youngest (aged 41-50 y) women (3.2%; 95% CI 1.11 to 5.18), approached 10% in women aged 51-55 years (7.1%; 95% CI 3.4 to 10.9), and reached 19.86% (95% CI 13.2 to 26.5) among the oldest women (aged 56-75 y). CONCLUSIONS: Physicians who opt to treat UTI in postmenopausal women empirically should consider prescribing drugs other than fluoroquinolones. Concomitant longitudinal surveillance of both antibiotic utilization patterns and uropathogen resistance rates should become routine practice in this managed-care organization.

Macrolide, lincosamide and tetracycline susceptibility and emm characterisation of invasive Streptococcus pyogenes isolates in Israel.

Group A beta-haemolytic streptococcus (GAS) causes a variety of infections, including life-threatening illnesses. Although the species is uniformly penicillin susceptible, resistance to other antibiotics is becoming more common. We studied the prevalence of resistance and associated factors in a nationwide, prospective, population-based study of invasive infections in Israel. Isolates were collected in collaboration with 24 hospitals in Israel during 1996-1999. Minimal inhibitory concentrations (MICs) of erythromycin (ERY), clindamycin (CLI) and tetracycline (TET) were determined as well as ERY and TET resistance phenotypes and genotypes. Five hundred isolates were examined: 136 (27.2%) were not susceptible to TET, 10 (2.0%) to ERY and 5 (1%) to CLI. ERY resistance was associated with emm types 12 and 83 (P<0.001 for both). MICs of TET had a bimodal distribution distinguishing sensitive and resistant populations. Non-susceptibility to TET was mainly due to the presence of tet(M) and was associated with T types 3, 3/13/B3624 and 9 and emm types 9, 33, 64, 73, 74, 76, 77 and 83. TET susceptibility was associated with T types 1, 2 and 11, emm types 1-4, 11, 12, 22, 26 and 75 and the presence of speA and speC. In Israel, resistance of invasive GAS isolates to ERY remains low and is associated with specific T and emm types, as is TET resistance. TET resistance is less frequent than previously reported in Israel and is associated with a lower prevalence of speA and speC.

Severe infections in thalassaemic patients: prevalence and predisposing factors.

The incidence of infections among patients with thalassaemia and the role of risk factors for infection are uncertain. We studied the occurrence of infections necessitating hospitalisation in 92 homozygous beta-thalassaemia patients who had been followed longitudinally for decades, and investigated the role of potential risk factors for these infections. Pneumonia accounted for 26% of the infections and fever of unknown origin for 14%. Staphylococcus aureus was the major pathogen possibly related to injections associated with intensive chelation with deferoxamine. There was a significant increase in the rate of infection over time, notably after 15 years. Splenectomy correlated with the incidence of infection (P < 0.001) without being confounded by other variables and with highest frequencies of infections present after 10 years. A direct correlation between iron overload and infection was evident only before the initiation of iron-chelating treatment (P < 0.01). Following initiation of deferoxamine, paradoxically, the infection rate increased (P = 0.046). The combination of splenectomy and deferoxamine treatment was associated with the highest adjusted infection rate. Parathyroid dysfunction and glucose-6-phosphate dehydrogenase deficiency were significantly associated with infection (P = 0.02 and P = 0.04 respectively). The infection rate in thalassaemia is affected mainly by the duration of the disease and is increased by splenectomy and, in the long term, by treatment with deferoxamine.

Physician speciality and adherence to guidelines for the treatment of unsubstantiated uncomplicated urinary tract infection among women.

PURPOSE: To evaluate the variance in rates of physician adherence to guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommending either trimethoprim-sulfamethoxazole (TMP-SMX) or nitrofurantoin, in all relevant physician subspecialities practising in a managed care community setting in Israel. METHODS: Data were derived from the computerised medical records of Maccabi Healthcare Services, a health maintenance organisation (HMO) in Israel providing care to more than 1.6 million members nation-wide. The study population included women aged 18-75 years without risk factors for complicated UTI who were treated empirically with antibiotics for a diagnosis of acute cystitis or UTI. The data set consisted of 64,236 initial physician-patient encounters from July 2000 to June 2002. Physician adherence to guidelines was calculated by comparing the proportion of cases treated with each individual drug. A binary regression model was used to evaluate factors associated with suboptimal adherence to the guidelines. RESULTS: Nitrofurantoin was the most frequently prescribed drug (18.51%), followed by TMP-SMX (17.04%) for a crude rate of adherence of 35.6%. Adherence was observed to be highest in cases treated by urologists (OR=2.8, 95%CI: 2.4, 3.3), followed by gynaecologists (OR=1.9, 95%CI: 1.7, 2.31), with family practice as the referent speciality. The medical school attended was also found to be significant. CONCLUSIONS: Physician speciality was found to be significantly associated with rate of adherence to guidelines, with higher rates being observed amongst specialities such as urologists who presumably have greater familiarity with the subject matter.

Clinical and epidemiological aspects of infections caused by fusarium species: a collaborative study from Israel.

Fusarium infections are an important problem worldwide, commonly affecting immunocompromised individuals. We conducted a retrospective study in two Israeli tertiary medical centers of factors predisposing to infection by Fusarium spp. and their influence on the epidemiology and clinical outcome of this infection. Fusarium spp. were isolated from 89 patients with a median age of 57 years. Sixty-eight patients were considered immunocompetent. Seven patients had disseminated disease, 34 had locally invasive disease, and 48 had superficial infection. Most infections were limited and occurred mainly in lower limbs. Factors associated with in-hospital mortality were chronic renal failure, hematological malignancy, immunosuppression, disseminated infection, and positive blood culture. Multivariate analysis showed that chronic renal failure, hematological malignancy, burns, and disseminated infection were independently associated with mortality. A surge in the frequency of infections was noticed during the summer for patients from rural areas, involving mainly the eyes and lungs. At one of the hospitals (in a mountainous area), there was an increase in the isolation rate over time.

Azithromycin versus comparative therapy for the treatment of community acquired pneumonia.

A 3-day course of azithromycin was compared with the 10 days of other antibiotics, which general practitioners routinely use as therapy for community acquired pneumonia (CAP). The study was a prospective open labelled, randomised, multicentre, comparative study from five family clinics. Patients with clinical and radiological evidence of pneumonia were included. The pneumonia resolved in 98.4% (61/62) of patients treated with azithromycin and in 87% (40/46) of patients treated with other antibiotics (P < 0.017). Restitution of normal function at home (2.3 +/- 1.2 and 4.3 +/- 2.6 days) and return to work (3.4 +/- 2.0 and 5.5 +/- 3.1 days) was more rapid among the group treated with azithromycin ( P < 0.001). Three days of azithromycin was more convenient and cost effective than the comparators used to treat pneumonia.

Iontophoresis-gentamicin delivery into the rabbit cornea, using a hydrogel delivery probe.

PURPOSE: To evaluate the efficacy of penetration of gentamicin into the cornea of rabbits using iontophoresis with a hydrogel-gentamicin containing probe. METHODS: Eight of 10 groups (groups 3-10) of 6 rabbits (one eye per rabbit), underwent corneal iontophoresis using soft stable hydroxyethyl methacrylate hydrogel discs (80% water content) loaded with gentamicin sulphate which were mounted on an iontophoresis probe. The studied current intensities were 0, 0.1, 0.3 and 0.6 mAmp, and the durations of iontophoresis were 10 and 60 sec. Two control groups received 1.4% topical drops of gentamicin every 5 min for 1 hr (group 1) or sub-conjunctival injection of 10 mg gentamicin (group 2). Following sacrifice, aqueous humour was taken, corneas were excised, and gentamicin concentration was determined in aqueous humour and cornea samples. RESULTS: Post-iontophoresis, the concentration of gentamicin in the corneas ranged from high (88.60 +/- 38.64 microg ml(-1)) to very low (0.10 +/- 0.89 microg ml(-1)). Both the control groups and those rabbits treated with current intensity of 0.1 mAmp or greater obtained therapeutic gentamicin levels in the corneas. Use of iontophoresis for 60 sec or current intensity greater than 0.1 mAmp obtained corneal gentamicin levels not different from sub-conjunctival injection. Application of current intensity of 0.1 mAmp or greater gave corneal gentamicin concentrations comparable to topical application of the drug, except when 0.6 mAmp were used for 60 sec (p = 0.05). Increasing current intensity or duration of iontophoresis significantly increased (p = 0.001 for both) gentamicin penetration into the cornea. Current intensity had more influence (Beta2 = 0.40) than duration (Beta2 = 0.13) on drug penetration. A significant interaction was found between the duration of iontophoresis and the current intensity. Very small or no concentrations of the drug were discovered in the anterior chambers of rabbits. CONCLUSIONS: Iontophoresis using hydrogel-gentamicin probe may deliver therapeutic concentrations of gentamicin into the cornea.

Systematic Inventive Thinking: a new tool for the analysis of complex problems in medical management.

The complexity of medical problems is a well-recognized phenomenon. In the presence of economic and cultural restrictions, medical decision-making can be particularly challenging. This paper outlines a system of analysis and decision-making for solving such problems, and briefly describes a case study in which the method was used to analyze the case of antibiotic overprescribing in a large health maintenance organization. The purpose of the study was to determine if a technique for problem-solving in the field of engineering could be applied to the complex problems facing primary care. The method is designated Systematic Inventive Thinking and consists of a three-step procedure: problem reformulation, general search-strategy selection, and an application of idea-provoking techniques. The problem examined is the over-prescribing of antibiotics by general practitioners working in Maccabi Healthcare Services, an HMO serving one and a half million patients in Israel. The group of healthcare professionals involved in the discussions generated 117 ideas for improving antibiotic use. Six of these ideas were then implemented in a national campaign in the winter of 2000/1 and 2001/2. During this period, a significant reduction in per-visit antibiotic purchasing was observed for influenza visits (from 79.2 per 1,000 to 58.1 per 1,000, P < 0.0001), but not for other categories of visits. The SIT methodology is a useful technique for problem-solving and idea generation within the medical framework.

Deep infection by Trichophyton rubrum in an immunocompromised patient.

Dermatophytes are common pathogens of skin but rarely cause invasive disease. We present a case of deep infection by Trichophyton rubrum in an immunocompromised patient. T. rubrum was identified by morphological characteristics and confirmed by PCR. Invasiveness was apparent by histopathology and immunohistochemistry. The patient was treated successfully with itraconazole.

Invasive group a streptococcal infections, Israel.

We conducted a prospective, nationwide, population-based study of invasive group A streptococcal infections in Israel. We identified 409 patients (median age 27 years; range <1-92), for an annual incidence of 3.7/100,000 (11/100,000 in Jerusalem). The mortality rate was 5%. Bacteremia occurred in 125 cases (31%). The most common illnesses were soft-tissue infection (63%) and primary bacteremia (14%). Thirty percent of patients had no identifiable risk factors for infection. Eighty-seven percent of pharyngeal carriers had the same serotype as the index patient. M types included M3 (25%), M28 (10%), and M-nontypable (33%). A marked paucity of M1 serotype (1.2%) was detected. The results highlighted concentrated pockets of invasive disease in the Jewish orthodox community (annual incidence 16/100,000).