Isolated endogenous endophthalmitis due to a sporodochial-forming Phialemonium curvatum acquired through intracavernous autoinjections.

We report a case of endogenous endophthalmitis due to a sporodochial-forming species of Phialemonium curvatum. The infection led to the enucleation of the affected eye, but there was no evidence of systemic dissemination. The isolated P. curvatum produced aggregates of phialides, many occurring on coils or in verticils, which eventually develop into sporodochia. The initial and post-enucleation isolates revealed they were identical to strains of P. curvatum from Israel causing disseminated disease in patients practicing intracavernous autoinjections for the treatment of erectile dysfunction. The reported case had unusual clinical and microbiological features. Despite the route of acquisition and the lack of systemic antifungal therapy, the infection did not spread beyond the eye. The morphology of the phialides aggregates was also unique, and the distinction between Volutella and Acremonium is discussed. This case expands the spectrum of infections due to Phialemonium species, and reveals a novel way of developing fungal endophthalmitis.

Characteristics of candidaemia with Candida-albicans compared with non-albicans Candida species and predictors of mortality.

Candidaemia due to non-albicans Candida species is increasing in frequency. We describe 272 episodes of candidaemia, define parameters associated with Candida albicans and other Candida species, and analyse predictors associated with mortality. Patients with C. albicans (55%) had the highest fatality rate and frequently received immunosuppressive therapy, while patients with Candida parapsilosis (16%) had the lowest fatality and complication rates. Candida tropicalis (16%) was associated with youth, severe neutropenia, acute leukaemia or bone marrow transplantation, Candida glabrata (10%) was associated with old age and chronic disease, and Candida krusei (2%) was associated with prior fluconazole therapy. The overall fatality rate was 36%, and predictors of death by multi-variate analysis were shock, impaired performance status, low serum albumin and congestive heart failure. Isolation of non-albicans Candida species, prior surgery and catheter removal were protective factors. When shock was excluded from analysis, antifungal therapy was shown to be protective. Unlike previous concerns, infection with Candida species other than C. albicans has not been shown to result in an increased fatality rate.

Blood invasiveness of Salmonella enterica as a function of age and serotype.

We explored the dual influence of the patient's age and the infecting serotype on the blood invasiveness patterns of non-Typhi Salmonella enterica (NTS). Blood invasiveness ratio (BIR) was calculated as the ratio between the number of blood and blood + stool isolates. Analysis of 14,951 NTS isolates showed that the BIR increased drastically above the age of 60 years, reaching levels 3.5-7 times higher compared to age group < 2 years. Different patterns of age-related invasiveness were observed for the five most common NTS serotypes (Enteritidis, Typhimurium, Virchow, Hadar, Infantis). Among children < 2 years, the BIR was highest for serotype Virchow and lowest for serotype Hadar, while in persons > or = 60 years it was highest for serotypes Enteritidis and lowest for serotype Infantis. The tendency of NTS serotypes to invade the bloodstream was significantly influenced by the patient's age, however the impact of age differed for various NTS serotypes.

Correlation between candiduria and departmental antibiotic use.

The incidence of candiduria is increasing in teaching hospitals. We examined the hypothesis that this trend was correlated with the amount of departmental antibiotic consumption. In the setting of a large teaching hospital in Israel, the correlation coefficient between departmental intravenous antibiotic consumption (expressed as daily defined dose (DDD)/1000 patient-days) and the incidence of candiduria per 1000 patient-days was 0.47 (P=0.03). For broad-spectrum antibiotics, the corresponding correlation coefficient was 0.66 (P=0.001). The strongest correlation with candiduria was shown for the use of meropenem (r=0.79, P<0.001) and ceftazidime (r=0.66, P=0.001). This is the first time that departmental habits of antibiotic use have been shown to be strongly correlated with the incidence of candiduria in hospitalized patients. These results add an important new dimension to the strategy of restricting broad-spectrum antibiotics.

Departmental consumption of antibiotic drugs and subsequent resistance: a quantitative link.

OBJECTIVE: To look for a quantitative model linking departmental consumption of antibiotic drugs to the subsequent isolation of resistant hospital-acquired coliform pathogens. MATERIALS AND METHODS: Included in the study were all patients with hospital-acquired bloodstream infections caused by a coliform pathogen, detected in six departments of internal medicine of one university hospital during the period 1991-1996, who had not been hospitalized in the month before the infection (n = 394). Departmental consumption of antibiotics in the year before the infection [expressed as defined daily dosages (DDD)/100 patient days], antibiotic treatment given to the individual patient before the infection, the day of hospital stay on which the infection occurred, and the department and the calendar year were all included in a logistic model to predict the isolation of a resistant pathogen. We looked at five drugs: gentamicin, amikacin, cefuroxime, ceftazidime and ciprofloxacin. RESULTS: Five logistic models were fitted for the resistance to each of the antibiotic drugs. The multivariable-adjusted odds ratios for a pathogen resistant to the specific antibiotic were 1.03 [95% confidence interval (CI) 0.70-1.50] for gentamicin, 1.80 (95% CI 1.00-3.24) for amikacin, 1.12 (95% CI 1.02-1.23) for cefuroxime, 1.45 (95% CI 1.19-1.76) for ceftazidime and 1.06 (95% CI 0.57-1.97) for ciprofloxacin, per 1 DDD/100 patient days. CONCLUSIONS: The departmental consumption of cephalosporin drugs and amikacin in six autonomous departments of medicine in the same hospital was associated with a measurable and statistically significant increase in the probability of infection caused by a resistant pathogen.

West Nile fever outbreak, Israel, 2000: epidemiologic aspects.

From August 1 to October 31, 2000, 417 cases of West Nile (WN) fever were serologically confirmed throughout Israel; 326 (78%) were hospitalized patients. Cases were distributed throughout the country; the highest incidence was in central Israel, the most populated part. Men and women were equally affected, and their mean age was 54+/-23.8 years (range 6 months to 95 years). Incidence per 1,000 population increased from 0.01 in the 1st decade of life to 0.87 in the 9th decade. There were 35 deaths (case-fatality rate 8.4%), all in patients >50 years of age. Age-specific case-fatality rate increased with age. Central nervous system involvement occurred in 170 (73%) of 233 hospitalized patients. The countrywide spread, number of hospitalizations, severity of the disease, and high death rate contrast with previously reported outbreaks in Israel.

Clinical characteristics of the West Nile fever outbreak, Israel, 2000.

West Nile (WN) virus is endemic in Israel. The last reported outbreak had occurred in 1981. From August to October 2000, a large-scale epidemic of WN fever occurred in Israel; 417 cases were confirmed, with 326 hospitalizations. The main clinical presentations were encephalitis (57.9%), febrile disease (24.4%), and meningitis (15.9%). Within the study group, 33 (14.1%) hospitalized patients died. Mortality was higher among patients >70 years (29.3%). On multivariate regressional analysis, independent predictors of death were age >70 years (odds ratio [OR] 7.7), change in level of consciousness (OR 9.0), and anemia (OR 2.7). In contrast to prior reports, WN fever appears to be a severe illness with high rate of central nervous system involvement and a particularly grim outcome in the elderly.

Excess mortality in women with hospital-acquired bloodstream infection.

PURPOSE: We examined the outcomes of bloodstream infection in men and in women and whether any sex-related differences were explained by underlying disorders, severity of disease, or clinical management. SUBJECTS AND METHODS: Using a prospectively collected database, we compared in-hospital mortality in men and women. We used multivariable logistic regression analysis to test whether sex-related differences could be due to potential confounders. RESULTS: Of 4250 patients with bloodstream infections, 1750 (41%) had hospital-acquired infections. The overall case fatality was 31% (625 of 2032) in women and 29% (631 of 2218, P = 0.1) in men. However, 43% (325/758) of the women with hospital-acquired infections died, compared with 33% (327/992) of the men (P = 0.0001). In a multivariate analysis, female sex was associated with greater mortality in patients with hospital-acquired infections (odds ratio = 1.7; 95% confidence interval: 1.1 to 2.6). The excess mortality in women was mainly seen in patients with major underlying disorders (fatality rate of 45% [234 of 525] in women vs. 32% in men [234 of 743, P = 0.0001). CONCLUSIONS: Mortality in women with hospital-acquired bloodstream infections is substantially greater than in men. The excess mortality was concentrated in women with severe underlying disorders, suggesting that sepsis might have accentuated differences in the outcome of underlying disorders in women.

Bacteraemia caused by hospital-type micro-organisms during hospital stay.

A sharp transition between community-type and hospital-type pathogens at the second or third day of hospital stay is often assumed. This study aimed to test whether such a threshold phenomenon exists for bloodstream infections and to examine the relationship between the proportion of infections caused by hospital-type pathogens and length of stay in the hospital. Blood stream infections were studied in a referral and a university hospital in west Denmark, and a university hospital in central Israel during three study periods (1994-1996, 1992-1995, 1989-1995 in the three hospitals respectively). No threshold effect at 2-3 days stay in the hospital could be demonstrated. However the percentage of Pseudomonas aeruginosa bloodstream infections increased constantly in the three hospitals from 1%, 1% and 7% during the first 2 days to 7%, 4%, and 14% during the third week of hospital stay (P<0.01 for all three comparisons-chi(2)for linear trends). For Candida sp. the increase was from 0%, 2%, 1% during the first 2 days to 3%, 4%, and 9% during the third week, P<0.05. Methicillin-resistant Staphylococcus aureus in Israel increased from 26% of the total number of S. aureus during the first 2 days to 69% during the third week, P<0.0001. For penicillin-resistant S. aureus in Denmark, the percentages were 84% and 100%, P<0.05.The percentage of infections caused by hospital-type pathogens increased almost linearly during the first 3 weeks of hospital stay, with no threshold effect. This trend should be taken into account when prescribing empirical therapy for nosocomial infections.

The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection.

OBJECTIVES: To test whether empirical antibiotic treatment that matches the in vitro susceptibility of the pathogen (appropriate treatment) improves survival in patients with bloodstream infections; and to measure the improvement. DESIGN: Observational, prospective cohort study. SETTING: University hospital in Israel. SUBJECTS: All patients with bloodstream infections detected during 1988-94. INTERVENTIONS: None. MAIN OUTCOME MEASURES: In-hospital fatality rate and length of hospitalization. RESULTS: Out of 2158 patients given appropriate empirical antibiotic treatment, 436 (20%) died, compared with 432 of 1255 patients (34%) given inappropriate treatment (P = 0.0001). The median durations of hospital stay for patients who survived were 9 days for patients given appropriate treatment and 11 days for patients given inappropriate treatment. For patients who died, the median durations were 5 and 4 days, respectively (P < 0.05), for both comparisons. In a stratified analysis, fatality was higher in patients given inappropriate treatment than in those given appropriate treatment in all strata but two: patients with infections caused by streptococci other than Streptococcus gr. A and Streptoccocus pneumoniae (odds ratio (OR) of 1.0, 95% confidence interval (95% CI) 0.4-2.5); and hypothermic patients (OR = 0.9, 95% CI = 0.3-2.4). Even in patients with septic shock, inappropriate empirical treatment was associated with higher fatality rate (OR = 1.6, 95% CI = 1.0-2.7). The highest benefit associated with appropriate treatment was observed in paediatric patients (OR = 5.1, 95% CI = 2.4-10.7); intra-abdominal infections (OR = 3.8, 95% CI = 2.0-7.1); infections of the skin and soft tissues (OR = 3.1, 95% CI = 1.8-5.6); and infections caused by Klebsiella pneumoniae (OR = 3.0, 95% CI = 1.7-5.1) and S. pneumoniae (OR = 2.6, 95% C = 1.1-5.9). On a multivariable logistic regression analysis, the contribution of inappropriate empirical treatment to fatality was independent of other risk factors (multivariable adjusted OR = 1.6, 95% CI = 1.3-1.9). CONCLUSION: Appropriate empirical antibiotic treatment was associated with a significant reduction in fatality in patients with bloodstream infection.

Necrotizing fasciitis caused by Staphylococcus aureus.

Two patients with rapidly progressive necrotizing fasciitis of a lower extremity due to Staphylococcus aureus as a single pathogen are described. In both patients the portal of entry was attributed to needle puncture (intra-articular injection and intravenous catheter, respectively), followed by bacteremia. Necrotizing fasciitis occurred in a site remote from the needle puncture, suggesting metastatic infection. One patient developed toxic shock syndrome and the other a sunburn-like rash and erythematous mucosae with strawberry tongue. One patient died, and the other required above-knee amputation due to secondary infectious complications. Staphylococcus aureus may mimic the presentation of invasive group A streptococcal infections. A history of needle puncture should alert the physician to the possibility of Staphylococcus aureus infection.

Monotherapy versus beta-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective, observational study.

The aim of the present study was to test whether the combination of a beta-lactam drug plus an aminoglycoside has advantage over monotherapy for severe gram-negative infections. Of 2,124 patients with gram-negative bacteremia surveyed prospectively, 670 were given inappropriate empirical antibiotic treatment and the mortality rate in this group was 34%, whereas the mortality rate was 18% for 1,454 patients given appropriate empirical antibiotic treatment (P = 0.0001). The mortality rates for patients given appropriate empirical antibiotic treatment were 17% for 789 patients given a single beta-lactam drug, 19% for 327 patients given combination treatment, 24% for 249 patients given a single aminoglycoside, and 29% for 89 patients given other antibiotics (P = 0.0001). When patients were stratified according to risk factors for mortality other than antibiotic treatment, combination therapy showed no advantage over treatment with a single beta-lactam drug except for neutropenic patients (odds ratio [OR] for mortality, 0.5; 95% confidence interval [95% CI], 0.2 to 1.3) and patients with Pseudomonas aeruginosa bacteremia (OR, 0.7; 95% CI, 0.3 to 1.8). On multivariable logistic regression analysis including all risk factors for mortality, combination therapy had no advantage over therapy with a single beta-lactam drug. The mortality rate for patients treated with a single appropriate aminoglycoside was higher than that for patients given a beta-lactam drug in all strata except for patients with urinary tract infections. When the results of blood cultures were known, 1,878 patients were available for follow-up. Of these, 816 patients were given a single beta-lactam drug, 442 were given combination treatment, and 193 were given a single aminoglycoside. The mortality rates were 13, 15, and 23%, respectively (P = 0.0001). Both on stratified and on multivariable logistic regression analyses, combination treatment showed a benefit over treatment with a single beta-lactam drug only for neutropenic patients (OR, 0.2; 95% CI, 0.05 to 0.7). In summary, combination treatment showed no advantage over treatment with an appropriate beta-lactam drug in nonneutropenic patients with gram-negative bacteremia.

Septic shock in bacteremic patients: risk factors, features and prognosis.

Of 4,289 episodes of bacteremia detected in 3,631 patients, septic shock was diagnosed in 453 episodes (10.5%). In 56% of shock episodes, septic shock developed more than 24 h after the first positive blood culture was taken. In a logistic regression analysis, variables predictive of septic shock were: advanced age [odds ratio (OR) of 1.015 for an increment of 1 year]; renal failure as an underlying disorder (OR = 1.47); neutropenia (OR of 2.26); curtailed functional capacity (OR of 1.54 for an increment of 1 category); unknown source of infection (OR = 1.66); anaerobic (OR = 2.86), polymicrobial bacteremia (OR = 1.54), or pathogens other than Streptococcus viridans (OR = 0.08 for Streptococcus viridans). The in-hospital mortality associated with septic shock was 80% vs 21% in episodes of bacteremia without shock, and shock episodes accounted for 31% of all deaths. The fatality rate in shock patients given appropriate empiric antibiotic treatment was 74.9% vs 84.7% in patients given inappropriate treatment (p = 0.01). Judging by the present results, host factors are more important determinants for development of septic shock in bacteremic patients than the type of pathogen. Even in patients with shock, appropriate empiric antibiotic treatment was associated with an improved chance of survival.

Multiple symmetric lipomatosis presenting with polyneuropathy.

We describe an unusual case of multiple symmetric lipomatosis (MSL) that presented with severe polyneuropathy, and review the literature. To the best of our knowledge, this is the first description of polyneuropathy as the presenting sign of MSL and the first report of this syndrome in Israel. MSL has to be included in the differential diagnosis of unexplained polyneuropathy.

Bacteraemia in a community and a university hospital.

Four hundred and forty-one and 1048 episodes of bacteraemia were prospectively surveyed over a period of 18 months in two hospitals, a 450 bed community hospital and a 900 bed tertiary care urban university hospital. Incidence of bacteraemia was 2.18 per 1000 hospitalization days (10.1 per 1000 admissions) in the community hospital and 2.64 per 1000 hospitalization days (12.0 per 1000 admissions (P < 0.004)) in the university hospital. Sixty six and 62% of episodes of bacteraemia were community acquired. The majority of bacteraemic episodes originated on the internal medicine wards of both hospital--46.7% and 58.7% respectively; the incidence of bacteraemia in the medical divisions of both hospitals was 23.1 and 17.5 per 1000 admissions respectively (P < 0.01). Overall mortality rates were 22% and 26.7% respectively. 39.9% and 44% of all isolates were Gram-positive pathogens. Escherichia coli was the commonest Gram-negative pathogen in both hospitals, particularly the community hospital--47.5% vs 32.8% (P < 0.005) of all Gram-negative pathogens, while Pseudomonas spp. were significantly more common in the university hospital--18.5% vs 11.8% (P < 0.02). Non-enterococcal streptococci were more common in the community hospital while enterococci were far more common at the university hospital--15.1% vs 1% of all Gram-positive pathogens (P < 0.05). Staphylococcus epidermidis was more common among the community hospital Gram-positive bacteraemias--31.1% vs 18.6% (P < 0.005). For almost all genera and species, antibiotic resistance was higher at the university hospital. Twenty nine point four per cent of Staphylococcus aureus isolates from the university hospital were methicillin resistant compared to 2.4% at the community hospital (P < 0.005). 29.4% of all Streptococcus pneumoniae isolates at the university hospital were penicillin resistant while no resistance was found at the community hospital. A high resistance rate to ofloxacin was found at the university hospital among S. aureus and Pseudomonas sp. Sources of bacteraemia did not differ significantly between the two hospitals. In conclusion, although outcome did not differ significantly for the two hospitals, there were significant differences between blood culture isolates in these two different settings. These differences may influence clinical decision-making about antibiotic therapy for patients in these hospitals.

Long-term survival following bacteremia or fungemia.

OBJECTIVE: To delineate long-term survival after an episode of bacteremia or fungemia and risk factors for mortality. DESIGN: Cohort study. SETTING: A 900-bed university hospital in Israel. PATIENTS: Study group comprising 1991 patients 18 years of age or older in whom bacteremia or fungemia were detected between March 1988 and October 1992, and a control group comprising 1991 inpatients without any infectious diseases, matched for age, sex, department, date of admission, and underlying disorders. INTERVENTIONS: None. MEASUREMENTS: Interval from the date of the first positive blood culture (study group) or from date of the identical hospital day (in the matched control patient) to the date of death as recorded in the Israeli National Population registry or, if alive, to June 1, 1994. RESULTS: The median age of patients was 72 years. In the study group, the mortality rate was 26% at 1 month, 43% at 6 months, 48% at 1 year, and 63% at 4 years, and the median survival was 16.2 months. In the control group, the mortality rate was 7% at 1 month, 27% at 1 year, and 42% at 4 years, and the median survival was greater than 75 months (P < .001). Factors significantly and independently associated with mortality in bacteremic patients were functional class (median survival, 0.5 month in bedridden patients), septic shock (median survival, 0.2 month), serum albumin (median survival, 1.1 months in the lowest quartile), serum creatinine (median survival, 2.9 months in the highest quartile), age (median survival, 2.9 months in the highest quartile [age > 80 years]), inappropriate empirical antibiotic treatment (median survival, 4.9 months), nosocomial infection (median survival, 9.6 months), and malignancy (median survival, 2.4 months). CONCLUSIONS: Bacteremia is associated with high short-term mortality, but also a sign of severely curtailed long-term prognosis, especially in patients with low functional capacity, low serum albumin, high serum creatinine, nosocomial infections, malignancy, inappropriate antimicrobial treatment, and septic shock and in elderly patients.

Prognostic significance of the neutrophil count in immunocompetent patients with bacteraemia.

To examine the prevalence of neutropaenia in immunocompetent, bacteraemic patients, and whether it carries an independent risk for mortality, we surveyed 2096 bacteraemic patients without malignant diseases, and who were not receiving cytotoxic drugs. The granulocyte count on the day of the first positive blood culture was < 1 x 10(9) cells/l in 33 patients (1.7%, group 1); 1.0-4.0 x 10(9) cells/l in 154 patients (7.9%, group 2); 4.0-8.0 x 10(9) cells/l in 564 patients (29%, group 3); 8.0-20.0 x 10(9) cells/l in 1034 patients (53%, group 4); and > 20.0 x 10(9) cells/l in 163 patients (8.4%, group 5). The mortality rates in the five groups were 39.4%, 18.8%, 18.1%, 25.7% and 25.8%, respectively (p = 0.0001). The main pathogens in group 1 were Staphylococcus aureus in 25% of patients and Pseudomonas sp. in 23%. Mortality in group 1 patients was higher than in the other patients (odds ratio 1.4, 95% CI 1.1-1.9]. Mortality was also significantly higher in group 2 patients with high blood urea nitrogen. The percentage of neutropaenia, septic patients without known risk factors for neutropaenia is small, but their mortality is high. Overall mortality in patients with relative neutropaenia (1.0-4.0 x 10(9) cells/l) is low, but a subgroup of patients with high blood urea nitrogen is at considerable risk for a fatal outcome. High leucocyte counts are also a marker of increased risk for mortality, but this association is not an independent prognostic factor.