Carriage rate of carbapenem-resistant Klebsiella pneumoniae in hospitalised patients during a national outbreak.

During a national outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Israel, we conducted a point prevalence survey to determine the extent of asymptomatic carriage. Subsequently, a retrospective case-control study was done, comparing carriers of CRKP with non-carriers, in order to detect risk factors for carriage. Oral, perianal and rectal swabs were obtained from all hospitalised eligible and consenting patients. Selective media for carbapenem-resistant Gram-negative bacteria were used and pulsed-field gel electrophoresis (PFGE) helped to determine clonal source. Culture was obtained from 298 patients. Sixteen (5.4%) were carriers of CRKP, with a higher carriage rate in medical and surgical wards. Only 18% of carriers were treated with any carbapenem prior to the survey. Five of the 16 carriers had a positive clinical specimen for CRKP, hence a clinical infection versus asymptomatic carriage ratio of 1:3. The rectum was the most sensitive site sampled, detecting 15/16 carriers, and the overall sensitivity of the method was 94% with a negative predictive value of 99.6%. In a multivariate analysis of risk factors for CRKP carriage, three variables were significantly related to carriage state: diaper use, longer duration of hospital stay and vancomycin use. PFGE demonstrated that all 16 isolates were identical, confirming clonal origin. A point prevalence survey performed at a single medical centre during an outbreak of CRKP demonstrated a carriage rate of 5.4%. The clonal origin of these isolates suggests that strict adherence to isolation procedure may contain this outbreak.

Q fever endocarditis; not always expected.

Q fever endocarditis is a chronic disease with protean manifestations. The clinical and serological manifestations of nine patients diagnosed as having Q fever endocarditis during a 19-year period are reviewed. Four patients (44%) required valve replacement due to congestive heart failure. Three of these four patients were diagnosed as having Q fever endocarditis only after elective valve surgery, by histopathological examination of the valve and subsequent serological tests. Prior to surgery they were afebrile and had no other symptom or sign indicative of endocarditis. The antibiotic treatment and the decreasing titres of Q fever antibodies of all nine patients during several years of follow-up are summarized. Careful assessment of heart valves for histopathological evidence of inflammation is suggested, even after elective replacement. If found, clinical and laboratory evaluation should include determination of anti-Coxiella burnetti antibodies.

Prevalence and predictive features of bacteremic urinary tract infection in emergency department patients.

The aim of this study was to determine the prevalence and predictive features of bacteremia among patients evaluated in the emergency department for urinary tract infection. Of the 350 patients with symptomatic urinary tract infection included in this retrospective study, 53 (15%; 95%CI 11.6-19.4%) were bacteremic. Five variables were independently associated with bacteremia: residence at home rather than in an institution (OR 4; 95%CI 1.5-10.7), presence of an indwelling urinary catheter (OR 3.3; 95%CI 1.3-8.8), presence of band forms in the blood count (OR 3.3; 95%CI 1.5-7.2), shaking chills (OR 2.3; 95%CI 1.1-4.8), and neutrophilia (OR 1.1; 95%CI 1.04-1.15). These easily assessable parameters may assist in the diagnosis of bacteremic urinary tract infection and the selection of empiric antibiotic treatment, thus potentially improving a patient's prognosis.

Extreme leukocytosis in the emergency department.

BACKGROUND: Extreme leukocytosis in the absence of haematological disease, is a topic about which little is known, although it may be associated with increased mortality among patients admitted to the intensive care department. The significance of extreme leukocytosis in patients presenting to hospital is uncertain. AIM: To study the correlates and prognostic significance of extreme leukocytosis, in patients admitted to an emergency department. DESIGN: Observational study. METHODS: Consecutive adult patients with extreme leukocytosis (>25 x 10(9)/l, n=54) presenting to the emergency department of a university-affiliated hospital were compared to age-matched controls (+/-5 years) with moderate leukocytosis (12-25 x 10(9)/l, n=118) presenting to the same department. Data were collected on demographic features, emergency room findings and hospital course. RESULTS: Patients with extreme leukocytosis were more likely to suffer from infectious disease (74% vs. 48%, p<0.01), to be hospitalized (100% vs. 80%, p<0.001), and to die (32.1% vs. 12.7%, p<0.01), and had a longer median length of stay (7.5 vs. 4.0 days, p<0.005). There was no significant difference in vital signs between the two groups. DISCUSSION: In our patients, extreme leukocytosis appeared to be predominantly caused by infectious disease, and was associated with a high case fatality rate. The degree of leukocytosis may provide prognostic information beyond that reflected in traditional vital signs.

Risk factors for bacteriuria due to Pseudomonas aeruginosa or Enterococcus spp in patients hospitalized via the emergency department.

To determine the incidence and risk factors related to isolation of Pseudomonas aeruginosa or Enterococcus spp from urine cultures obtained from patients in the emergency department (ED), a 1-year prospective study was conducted of all urine specimens collected in the ED of a general hospital. Specimens from which one of these organisms was isolated at a concentration of >or=10(5) cfu/ml were included. Of 744 positive urine cultures, 39 (5%) were P. aeruginosa and 28 (4%) Enterococcus spp. Comparison with a control cohort of 80 patients with Escherichia coli bacteriuria revealed several univariate indicators for P. aeruginosa bacteriuria, including male sex, indwelling catheter, past prostatectomy, hospitalization in the previous 2 months and pregnancy; multivariate indicators were indwelling catheter (p<0.001) and male sex (p<0.001). Enterococcus and P. aeruginosa were significantly more often associated with asymptomatic bacteriuria. These data will help clinicians select appropriate antibiotic treatment for patients with urinary tract infections.

Assessment of the clinical significance of production of extended-spectrum beta-lactamases (ESBL) by Enterobacteriaceae.

BACKGROUND: We conducted a retrospective, cohort-controlled study to evaluate the effect of extended-spectrum beta-lactamase (ESBL) production by Enterobacteriaceae isolated from blood cultures, and of third or fourth generation cephalosporin treatment, on outcome. METHODS: Four hundred and fifty patient-unique Enterobacteriaceae, isolated from blood cultures during 2000 (before routine ESBL testing was introduced), were tested for ESBL by double-disk method and by E-test, assessing cefotaxime, ceftazidime and cefpodoxime, with and without clavulanate. Cases consisted of ESBL-positive (+) samples, originally reported as ceftazidime-susceptible; controls were ESBL-negative (-). Patient records were extensively reviewed. RESULTS: We identified 68 Enterobacteriaceae that were ESBL(+); they were compared with 186 ESBL(-) control organisms. Patients with sepsis due to an ESBL(+) organism more often had nosocomial infection, resided in nursing homes, were functionally dependent, had an indwelling catheter, had Klebsiella, and had a lower serum albumin level (all p < 0.001). Survival of patients with ESBL(+) and ESBL(-) sepsis was, respectively, 71% and 84% (p < 0.05). Multivariate analysis revealed that the only independent risk factor for death was a low serum albumin. Neither empiric nor definite treatment with cephalosporins was found to be an independent risk factor for death. Subset analysis was conducted on 15 patients with ESBL(+) sepsis and 21 controls with ESBL(-) sepsis, who had been treated with ceftazidime or cefepime only. In this subset, ESBL(+) patients more often resided in nursing homes (< 0.05), they had a significantly lower APACHE-II score (< 0.01) and the infection was more often nosocomial (< 0.005). Survival of ESBL(+) and ESBL(-) patients was 67% and 71%, respectively (NS). Time till defervescence did not differ between cases and controls. CONCLUSION: Mortality of patients with ESBL(+) sepsis was higher than that of patients with ESBL(-) sepsis. The reason appears to be related to other factors rather than to empiric treatment with cephalosporins or the nature or resistance pattern of the organism. This, at least, appears to be the case for patients with urosepsis, who constituted the majority of patients in this study.

Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram.

OBJECTIVE: To determine normal concentrations of procalcitonin in preterm infants shortly after birth and to assess its accuracy in detecting bacterial infection. METHODS: Blood samples of 100 preterm infants were prospectively drawn during the first 4 days of life for determination of procalcitonin concentration. Infants were classified into four groups according to their sepsis status. RESULTS: Mean (SD) gestational age and birth weight were 32 (2.9) weeks and 1682 (500) g respectively. A total of 283 procalcitonin concentrations from healthy infants were plotted to construct nomograms of physiologically raised procalcitonin concentration after birth, stratified by two groups to 24-30 and 31-36 weeks gestation. The peak 95th centile procalcitonin concentration was plotted at 28 hours of age; values return to normal after 4 days of life. Only 12 infants were infected, and 13 of their 16 procalcitonin concentrations after birth were higher than the 95th centile, whereas samples taken at birth were lower. In a multivariable analysis, gestational age, premature rupture of membrane, and sepsis status influenced procalcitonin concentration independently, but maternal infection status did not. CONCLUSIONS: The suggested neonatal nomograms of preterm infants are different from those of term infants. Procalcitonin concentrations exceeding the 95th centile may be helpful in detecting congenital infection, but not at birth.

Group A streptococcus bacteraemia: comparison of adults and children in a single medical centre.

Group A streptococcus (GAS) bacteraemia is often associated with soft-tissue infection, with significant morbidity and mortality. Little is known concerning the differences between adults and children with GAS bacteraemia. Records for 98 of 116 cases of GAS bacteraemia (60 adults and 38 children, aged 7 days to 96 years) occurring during a 10-year period (1993-2002) were located and reviewed. GAS bacteraemia comprised 0.6% of all bacteraemias in adults, compared to 3.3% in children (p < 0.001). The rate of adult GAS bacteraemia was two cases/1000 hospitalisations, compared to 13/1000 in children (p < 0.001). Seventy-six (78%) patients had concomitant tissue involvement, with skin or soft-tissue infection being the most common (62%). Fifty-three (88%) of 60 adults and five (13%) of 38 children had underlying conditions (p < 0.001). Twelve patients died, only one of whom was a child. Parameters associated with mortality were older age, lower temperature, hypotension, a need for surgical intervention, toxic shock syndrome, disseminated intravascular coagulation, thrombocytopenia, lymphopenia, hypocalcaemia, renal failure and acidosis (p < 0.05).

Prospective hospital-wide studies of 505 patients with nosocomial bacteraemia in 1997 and 2002.

We conducted surveys in 1997 and 2002 to determine the rate, underlying sources and outcome of nosocomial bacteraemia. Blood culture results were reviewed daily. All patients with positive cultures drawn >or=48 h after hospitalization were included in the study and their charts were reviewed. The underlying source of infection was determined by pre-defined clinical and/or microbiological criteria. Patients were followed until discharge or death. In 1997 and 2002, 851 and 857 patient-unique cases of bacteraemia were diagnosed, respectively, excluding contaminants; of these, 228 (27%) and 277 (32%) cases, respectively, were hospital acquired (P<0.05). The overall rate decreased from 7.5 to 7.0 per 1,000 admissions (P<0.001). The sources of bacteraemia in 1997 and 2002, respectively, were: intravascular catheters (36% and 27%, P<0.05), urinary tract (8% and 15%, P<0.05), respiratory tract (5% and 13%, P<0.01) and surgical sites (14% and 4%, P<0.001). In one-third of patients, the source of bacteraemia could not be determined. Only 52% and 54%, respectively, of these patients were discharged alive (difference was not significant). In 1997, Staphylococcus aureus was the most frequent isolate (26%), followed by coagulase-negative Staphylococcus (13%) and Klebsiella pneumoniae (11%). By 2002, the incidence of S. aureus had fallen to 11% (P<0.001), acinetobacter was the single most frequently isolated organism (increased from 6% to 17%) (P<0.001). In-hospital mortality associated with acinetobacter bacteraemia (57%) was significantly higher than that for other organisms (31-43%) (P<0.05). In conclusion, prospective surveys of nosocomial bacteraemias provide valuable information, facilitating the pursuit of successful interventions.

Non-Typhi Salmonella gastroenteritis in children presenting to the emergency department: characteristics of patients with associated bacteraemia.

The records of children with Salmonella gastroenteritis only (n = 97), and those with associated bacteraemia (n = 64), seen in one medical centre during a 12-year period, were analysed retrospectively. Mean patient age was 2.24 +/- 2.8 years (range, 0.05-16 years), and 49% were male. Children with bacteraemia presented after a longer duration of symptoms (7.0 +/- 6.9 vs. 3.9 +/- 4.6 days, p 0.0002), and had higher erythrocyte sedimentation rates (45 +/- 22 vs. 33 +/- 22 mm/h, p < 0.02) and lactate dehydrogenase values (924 +/- 113 vs. 685 +/- 165 IU/L, p 0.001). There was a trend in bacteraemic children towards immunosuppression (6.3% vs. 1.0%, p 0.08) and a lower number of siblings (2.9 +/- 1.9 vs. 3.8 +/- 2.7, p 0.063). Non-bacteraemic children had a more severe clinical appearance, and a higher percentage had a moderate to bad general appearance (51.5 vs. 29.7%, p < 0.01), with dehydration (37.1 vs. 18.8%, p 0.02) and vomiting (58.8 vs. 39.0%, p 0.02). Laboratory dehydration indicators were also markedly worse in non-bacteraemic children, with urine specific gravity of 1020 +/- 9.4 vs. 1013 +/- 9.0 (p 0.0002), base excess of - 4.2 +/- 3.0 vs. - 2.5 +/- 3.4 mEq/L (p 0.01), and blood urea nitrogen of 10.1 +/- 7.0 vs. 7.4 +/- 4.5 mg% (p 0.002). Thus, the clinical presentation of bacteraemic children was more gradual, and associated gastroenteritis and dehydration was less pronounced. These findings may contribute in part to the inadvertent discharge of bacteraemic children from the emergency department.

Glucose-6-phosphate dehydrogenase activity in male premature and term neonates.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is higher in term neonates than in adults. Some studies have suggested that activity may be even higher in preterm infants. OBJECTIVES: To determine if G6PD activity is higher in preterm than term neonates, and whether higher activity would interfere with diagnosis of G6PD deficiency in premature infants. METHODS: G6PD activity was determined in the first 48 hours after delivery in male premature, term, and near term infants. G6PD deficient neonates were separated, and the remaining premature infants compared with healthy, male, G6PD normal, near term and term neonates. RESULTS: Ninety four premature infants (mean (SD) gestational age 31.9 (3.8) weeks (range 23-36)) were studied. In four, G6PD activity was 0.8-1.8 U/g haemoglobin (Hb), which is clearly in the deficient range with no overlap into the normal range. G6PD activity in the remaining premature infants was significantly higher than in 24 near term and term neonates (gestational age > or = 37 weeks) (14.2 (4.6) v 12.0 (3.8) U/g Hb). Further analysis showed that significance was limited to those born between 29 and 32 weeks gestation, in which group G6PD activity was significantly higher than in those born before 29 weeks gestation, at 33-36 weeks gestation, and > or = 37 weeks gestation. CONCLUSIONS: G6PD activity is higher in premature infants born between 29 and 32 weeks gestation than in term neonates. This did not interfere with diagnosis of G6PD deficiency.

Susceptibility trends in bacteraemias: analyses of 7544 patient-unique bacteraemic episodes spanning 11 years (1990-2000).

The aim of the present study was to design more accurate tools for the selection of appropriate antimicrobial therapy for hospitalized patients with suspected sepsis. We created a large database comprising data on all patient-unique blood cultures obtained over an 11 year period (1 January, 1990 through 31 December, 2000). Improved statistical tools were applied to assess the trends in in vitro activity of individual antibiotic agents against various bacteria over time, and to calculate susceptibility rates of subsets of organisms. During the 11 year study period, 173571 blood cultures were obtained, of which 17703 (10.2%) were positive, with 7544 patient-unique blood cultures (4.3%). The mean annual number of positive, patient-unique cultures was 686 (standard deviation=79). The 10 most frequently isolated organisms were: Escherichia coli (1494), Staphylococcus aureus (1240), Klebsiella pneumoniae (779), Enterococcus spp. (631), Pseudomonas aeruginosa (488), Streptococcus pneumoniae (447), Enterobacter spp. (338), Acinetobacter spp. (298), Proteus mirabilis (260) and Candida spp. (254). No significant change was detected in the annual rates (means, standard deviations) per 1000 admissions of these organisms: the highest was E. coli (5.5, 1), the lowest was Candida (1, 0.3). Forty percent of organisms (N=2943) were obtained from patients in the emergency department (ED), 23% (1744) in medical departments, 15% (1134) in paediatric units, 13% (998) on surgical wards and 9% (709) in intensive care units (ICUs). Trend statistical analysis revealed a significant decrease in susceptibility in ED Enterobacteriaceae to eight of 15 (53%) tested antimicrobials, with a mean annual decrease of 1.6%+/-0.6%, in the ICU isolates, a significant decrease was detected in only five (33%) of the tested antimicrobials, with a mean annual decrease of 2.5%+/-1.3%. The difference in susceptibility between ED and ICU isolates was significant for all antimicrobials (P<0.001). A significant decrease in the susceptibility of E coli to nine of 15 drugs (60%) was detected, ranging from 0.7% to 2.7% annually. In K. pneumoniae a significant decrease in susceptibility of K. pneumoniae was detected with only two agents. Pseudomonas spp. isolates remained highly sensitive to all traditional anti-pseudomonal agents, without significant decay in sensitivity rates over time. Susceptibility of S. aureus to methicillin decreased significantly for several subsets of patients (P<0.001). Marked differences in susceptibility rates between the departments were detected. Trend statistical analyses, when appropriately applied to multi-year databases of microbial susceptibilities, may yield susceptibility tables that are significantly more accurate than traditional semi-annual or annual tables.

Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection.

OBJECTIVES: To define the incidence of congenital cytomegalovirus (CMV) infection in a defined population in Israel as diagnosed by urine polymerase chain reaction (PCR), and to assess the utility of this method for screening for congenital CMV infection. DESIGN: A convenient sample of urine specimens from asymptomatic newborns were subjected to CMV PCR. Positive results were validated by urine tube culture and by determination of serum CMV IgM antibodies. Maternal CMV IgG was determined in a representative sample of mothers. Newborns with positive urine specimens underwent full clinical evaluation. Epidemiological characteristics of the mothers were extracted from the medical records. SETTINGS: Two medical centres in Israel with different population characteristics. PATIENTS: A total of 2000 newborns (1000 in each medical centre). MAIN OUTCOME MEASURE: Presence of CMV DNA in the urine. RESULTS: Despite significant epidemiological differences between the populations in the two hospitals, the CMV seroprevalence was similar, 80.5% and 85%. Fourteen of the 2000 newborns screened (0.7%) were PCR positive. Urine culture was positive in nine of 10 specimens; IgM was positive in only two of 13 newborns with positive PCR. Eleven newborns underwent full or partial evaluation, and only one (9%) was symptomatic. CONCLUSIONS: The incidence of congenital CMV infection in the study population was 0.7%; over 90% were asymptomatic. Urinary CMV PCR is a reliable, rapid, and convenient method, and thus may serve as a screening tool for the detection of congenital CMV infection.

Use of time-trend analysis in the design of empirical antimicrobial treatment of urinary tract infection.

Selection of empirical treatment of hospitalized patients with urinary tract infection (UTI) is usually based on the results of urine culture as obtained from the local microbiology laboratory. In order to improve the precision and reliability of traditional methods, we analyzed temporal changes in the results of urine culture and antibiograms and stratified the results by inpatient department and the presence/absence of an indwelling catheter. The database consisted of urine cultures obtained during the first 3 months of each year over a 10-year period between 1991 and 2000. Only urine samples that grew a single organism at a concentration of >10(5) cfu were included in the analysis. Trend statistical tools, readily available but thus far not used for microbiological analyses, were applied to assess the decay in activity of individual antibiotic agents over time and to calculate susceptibility rates of organisms in subsets of urine samples. Organisms, antimicrobial susceptibility rates and the degree of decay in antimicrobial susceptibility rates varied significantly according to the location of the patient in the hospital and the presence of an indwelling catheter. Stratified trend analysis is a useful tool that can be helpful in designing and adapting clinical guidelines for the selection of appropriate empirical antibiotic treatment for the individual patient with urinary tract infection.

Chitotriosidase deficiency in survivors of Candida sepsis.

The existence of chitotriosidase, a human chitinolytic enzyme, hydrolyzes artificial chitotrioside substrates, but its specific function in humans is unknown. The homologous chitinases have an anti-fungal action in plants. In patients with Gaucher disease, chitotriosidase activity is markedly elevated and is a marker for response to specific treatment. In all populations, 6% of individuals are enzyme deficient but completely healthy. It was hypothesized that chitotriosidase deficient persons may be more vulnerable to fungal infections. Thus, the objective of the study was to ascertain the prevalence of homozygosity for the mutation of chitotriosidase among survivors of Candida sepsis. The prevalence of homozygosity among survivors was similar to that in the normal population. Although the cohort is the largest of its kind, since only survivors were tested, further studies should include all patients with Candida sepsis for comparison of survival rates among deficient versus sufficient individuals, and thereby elucidate if this enzyme has an anti-fungal function in man. Several theories are considered to explain the results.

Plasma chitotriosidase activity in patients with beta-thalassemia.

Variable increases in chitotriosidase levels have been reported in Italian patients with beta-thalassemia major and intermedia. We measured plasma chitotriosidase levels in Israeli patients with beta-thalassemia to ascertain its use as a universal marker of disease and/or response to therapy. Chitotriosidase levels in 39 adults (16-53 years; 30 with beta-thalassemia major, 9 with intermedia), and in 14 children (0.7-15 years; 12 with beta-thalassemia major, 2 with intermedia) were compared with other measures of disease, such as ferritin, hemoglobin, liver function tests, and genotype. Plasma chitotriosidase levels were normal (0.37 +/- 0.04 mU/mL) in all children. Twelve adults (31%) had elevated levels (>1.33 mU/mL): 11 patients (37%) with thalassemia major and 1 patient (11%) with thalassemia intermedia. A significant correlation was only found between plasma chitotriosidase levels and ferritin levels, and with mean number of transfusions per year. The patient with the highest chitotriosidase (1,440 nmol/mL/hr) had the highest ferritin (5,175 microg/L), required the most transfusions per year (40), and had abnormal liver tests. Normal chitotriosidase levels in the pediatric cohort and increased levels in only some adults may reflect status of iron overload in macrophages; thus there may be a role for monitoring chitotriosidase in patients with beta-thalassemia. Our results confirm results of the Italian cohort; however, in the latter, a more universal correlation was noted and chitotriosidase levels were much higher.

Elevation of ELISA d-dimer levels in patients with primary pulmonary hypertension.

BACKGROUND: Vasoconstriction, vascular wall remodeling and thrombosis are considered as possible etiologies of primary pulmonary hypertension (PPH). D-dimer, a degradation product of fibrin, has been increasingly used as a marker and prognostic factor in various diseases. OBJECTIVE: To assess elevated ELISA D-dimer levels as a marker of endogenous fibrinolysis in patients with PPH. PATIENTS AND METHODS: Comparison of ELISA D-dimer levels of 12 PPH patients (11 female, 1 male) aged 27-73 years (median 51 years) with those of sex- and age-matched healthy controls. RESULTS: Eleven patients had New York Heart Association (NYHA) class III or IV symptoms, and one patient had NYHA class II symptoms. All patients with PPH were treated with anticoagulants and vasodilators: 5 patients were treated with continuous intravenous prostacyclin, 4 patients with continuous UT-15 and 2 patients with intermittent intravenous iloprost. Mean ELISA D-dimer levels +/- SD were significantly higher in the PPH group than in the matched control group (473 +/- 109 vs. 182 +/- 103 ng/ml; mean difference: 291 +/- 79, 95% CI: 240-341, p < 0.0001). CONCLUSION: These results suggest the possible involvement of endogenous fibrinolysis in the pathophysiology of PPH.