Clinical significance of Staphylococcus saprophyticus identified on blood culture in a tertiary care hospital.

Staphylococcus saprophyticus is a well-known cause of acute uncomplicated urinary tract infection in young women. However, the clinical significance of this organism isolated from blood culture has not been determined. We assessed the clinical significance and characteristics of S. saprophyticus identified on blood culture. A total of 24 patients were identified, and 7 patients (29.2%) were considered to have clinically significant bacteremia. Of the 7 patients with clinically significant bacteremia, hematologic malignancy was the most common underlying illness (5 patients), and tunneled-central venous catheter was the most common portal of entry (4 patients). In no case did S. saprophyticus bacteremia originate from the urinary tract. One patient died during hospitalization. However, the death was not directly related to bacteremia. In conclusion, our data suggest that bacteremia caused by S. saprophyticus is most commonly associated with tunneled-central venous catheter in patients with hematologic malignancies and may be associated with a lower risk of mortality.

Risk factors and outcome for breakthrough candidaemia in patients with cancer.

While candidaemia that develops during systemic antifungal prophylaxis or therapy [breakthrough (BT) candidaemia] has been reported increasingly, the risk factors and outcome of BT candidaemia are not yet known definitely. We evaluated a consecutive series of cancer patients with candidaemia at Asan Medical Center during 6 years to identify risk factors and outcome in BT candidaemia comparing with non-BT candidaemia. Fifty-four episodes of candidaemia in cancer patients diagnosed during this period were reviewed retrospectively. There were 10 episodes (18.5%) of BT candidaemia in which the species distribution and frequency of catheter-related infection in the BT and non-BT groups were similar. BT candidaemia had a tendency to occur more frequently in patients with haematological than non-haematological diseases. Profound neutropenia and disseminated candidiasis were more common in the BT group; however, these differences were not statistically significant (P = 0.17 and 0.07 respectively). The duration of prior antibiotic therapy and duration of profound neutropenia (<100 mm(-3)) were identified as risk factors for BT candidaemia (P < 0.01 and 0.02 respectively) in univariate analysis and the latter was the only risk factor in multivariate analysis. The death rates due to candidaemia were 85.7% in the BT group and 42.9% in the non-BT group (P = 0.08); however, BT candidaemia alone did not increase mortality rate.

Economic evaluation of intravenous itraconazole for presumed systemic fungal infections in neutropenic patients in Korea.

Systemic fungal infections remain a major clinical problem in immunocompromised patients. Presumed systemic fungal infections (PSFI) are treated empirically with an intravenous antifungal agent to reduce the occurrence of documented infections and associated mortality. The objective of this study was to compare the cost-effectiveness of intravenous itraconazole (IVitra) treatment with the current first-line empirical treatment of PSFI with conventional amphotericin B (CAB) in cases of neutropenic cancer and bone marrow transplantation (BMT). Cost-effectiveness was expressed as cost per additional "responder" (defined as a patient without fever or major toxicity). We developed a medical decision analytical tree that included probabilities of toxicity, response and pathogen documentation, and second-line treatments. Clinical data were obtained from randomized clinical trials, and resource use data were obtained from a panel of clinical experts. The total cost of treating PSFI per neutropenic cancer patient was lower for IVitra than for CAB, and this lower cost resulted from a reduced need for second-line antifungals. In a cost-effectiveness analysis, IVitra treatment was superior to CAB treatment. Compared with current treatment with CAB, IVitra therapy was shown to be a cost-effective and cost-saving empirical treatment for PSFI in neutropenic cancer patients and BMT patients.

Characterization of erythromycin-resistant Streptococcus pneumoniae in Korea, and In Vitro activity of telithromycin against erythromycin-resistant Streptococcus pneumoniae.

To characterize the phenotypes and genotypes of erythromycin-resistant clinical isolates of Streptococcus pneumoniae in Korea and to evaluate the in vitro activity of telithromycin against these erythromycin-resistant isolates, we tested a total of 676 isolates of S. pneumoniae collected from 1997 to 2002 in a tertiary hospital in Seoul, Republic of Korea. MICs for erythromycin and telithromycin were determined by the agar dilution method. The macrolide resistance phenotypes of erythromycin-resistant isolates were determined by the erythromycin- clindamycin-rokitamycin triple disk (ECRTD) and MIC induction tests, whereas their macrolide resistance genotypes were determined by PCR for the erm(B), erm(A), subclass erm(TR), and mef genes. To discriminate between mef(A) and mef(E), PCR-restriction fragment length polymorphism (RFLP) analyses were performed. Of the 676 S. pneumoniae isolates, 459 (67.9%) were resistant to erythromycin. Of the 459 erythromycin-resistant isolates, 343 (74.7%) were assigned to the cMLS phenotype, 48 (10.4%) to the iMcLS phenotype, 4 (0.9%) to the iMLS phenotype, and 64 (14.0%) to the M phenotype. The erm(B) gene was detected in 251 (54.6%) isolates, the mef gene was detected in 64 (14.0%), and both the erm(B) and mef genes were detected in 144 (31.4%) isolates. All of the mef genes detected were identified as mef(E). Of the 459 erythromycin- resistant isolates, all but one were susceptible to telithromycin. The MIC(50)/MIC(90) to telithromycin of isolates carrying erm(B), mef(E), and both genes was 0.06/0.5 microg/ml, 0.03/0.125 microg/ml, and 0.5/1.0 microg/ml, respectively. Although the MICs of telithromycin for the erythromycin-resistant isolates varied according to genotype, telithromycin was very active against these erythromycin-resistant S. pneumoniae.

Increasing incidence of quinolone resistance in human non-typhoid Salmonella enterica isolates in Korea and mechanisms involved in quinolone resistance.

OBJECTIVES: We investigated the trends of nalidixic acid resistance in human non-typhoid Salmonella enterica in a Korean population, and examined some possible mechanisms involved in this resistance. METHODS: A total of 261 clinical strains were tested. For all strains, the MICs of nalidixic acid were determined. Nalidixic acid-resistant strains underwent further analysis, including determination of MICs of other antibiotics, mutation analysis within the topoisomerase genes, organic solvent tolerance test, western blotting for AcrA, marOR mutation analysis, ciprofloxacin accumulation test, and PCR for the qnr gene. The clonal relationships of Salmonella strains were examined by random amplified polymorphic DNA analysis. RESULTS: The incidence of nalidixic acid resistance increased from 1.8% in 1995-96 to 21.8% in 2000-02. The resistance rate was higher in S. enterica serotype Enteritidis (21.6%) than in serotype Typhimurium (12.1%). The nalidixic acid resistance rates in Salmonella Enteritidis varied according to the phage type (PT) and Salmonella Enteritidis PT 1 was most commonly associated with resistance to nalidixic acid. Several cases of clonal spread, especially by Salmonella Enteritidis PT 1, were identified. Of the 46 nalidixic acid-resistant strains, 43 had single mutations in the gyrA gene. Four strains were organic solvent-tolerant and were associated with decreased ciprofloxacin accumulation; three of these showed increased expression of AcrA and had novel mutations in marOR (84L). The qnr gene was not identified. CONCLUSIONS: Recently, the rate of nalidixic acid resistance in Korean clinical Salmonella strains markedly increased and it was partly due to the clonal spread of Salmonella Enteritidis, especially PT 1. The main mechanism of nalidixic acid resistance was a mutation in the gyrA region.

Risk factors for the acquisition of carbapenem-resistant Klebsiella pneumoniae among hospitalized patients.

The isolation of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported. However, no study analyzing potential risk factors for the acquisition of CRKP has been published as of now. We therefore performed a case-control study to determine the risk factors for the acquisition of CRKP. CRKP was nosocomially isolated from 30 patients between January 1997 and August 2003. Control patients were randomly selected at a ratio of 4:1 from the same medical or surgical services from which patients were receiving care when isolation of CRKP occurred. Risk factors for CRKP were previous use of carbapenem (adjusted odds ratio [AOR], 28.68; 95% confidence interval [CI], 9.08-90.55) and cephalosporin (AOR, 4.10; 95% CI, 1.35-12.43). In contrast, previous use of fluoroquinolone was negatively associated with isolation of CRKP (AOR, 0.26; 95% CI 0.07-0.97); however, the possibility of selection bias cannot be ruled out. Our results suggest that the nosocomial isolation of CRKP is strongly favored by the selection pressure of carbapenem.

Clinical significance of untreated Candida species isolated from ascites in cirrhotic patients.

The clinical significance of Candida species isolated from cirrhotic ascites is still unknown. We reviewed the clinical and laboratory features of all cirrhotic patients whose ascites samples were positive for Candida species. A total of 21 cirrhotic patients was identified. Patients were regarded as having peritonitis if they had 1 or more clinical symptom(s) or sign(s) in the absence of any other possible explanation. 10 patients (47.6%) were classified into the spontaneous Candida peritonitis (SCP) group, and the remaining 11 patients (52.4%) were classified into asymptomatic candidascites. Mortalities were higher in the SCP group at discharge (50.0% vs 27.3%), 6-month (90% vs 45.5%) and 1-y (100% vs 54.5%) (p=0.007). Receiver-operating characteristic curve analysis revealed that the cut-off value of ascitic fluid polymorphonuclear cell count of 315/mm(3) (0.315 x 10(9)/l) had the highest diagnostic accuracy with both sensitivity and specificity of 1.0. In conclusion, Candida species are associated with a grave outcome when manifested with peritonitis.

Clinical features and outcomes of bacteremia caused by Enterococcus casseliflavus and Enterococcus gallinarum: analysis of 56 cases.

The clinical significance and virulence potential of Enterococcus casseliflavus/flavescens and Enterococcus gallinarum are still uncertain. We retrospectively analyzed 56 cases of significant bacteremia caused by E. casseliflavus or E. gallinarum. Of these cases, 25 (44.6%) were associated with polymicrobial bacteremia, and 43 (76.8%) were associated with entry via the biliary tract. Resistance to vancomycin was observed in 17 (30.4%) of these 56 patients, and this resistance was significantly associated with E. gallinarum bacteremia (adjusted odds ratio [AOR], 10.56; 95% confidence interval [CI], 2.41-46.27) and bacteremia without biliary tract origin (AOR, 6.74; 95% CI, 1.44-31.67). The crude mortality rate was 13%, and the bacteremia-related mortality rate was 1.9%. In conclusion, bacteremia due to E. casseliflavus and E. gallinarum is commonly associated with biliary tract disease and may be associated with a low risk of mortality.

Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: a case-control study.

Risk factors for the nosocomial occurrence of imipenem-resistant Acinetobacter baumannii (IRAB) were determined. A case-control study design was used for a comparison of two groups of A. baumannii-positive patients with control patients. Nosocomial IRAB was isolated from the first group of A. baumannii-positive patients, and imipenem-susceptible A. baumannii (ISAB) was isolated from the second group. The control patients were randomly selected in a 4:1 ratio from the same medical or surgical services from which the A. baumannii-positive patients were receiving care when the isolation of IRAB occurred. Risk factors analyzed included demographic variables, comorbid conditions, variables related to hospitalization, and the antimicrobials used. IRAB was isolated from 104 patients, and ISAB was isolated from 387 patients between January and December 2000. The risk factors for IRAB were a previous intensive care unit (ICU) stay (odds ratio [OR], 21.54; 95% confidence interval [CI], 10.73 to 43.23) and prior exposure to imipenem (OR, 9.18; 95% CI, 3.99 to 21.13) or third-generation cephalosporins (OR, 2.11; 95% CI, 1.13 to 3.95). Risk factors for ISAB were a previous ICU stay (OR, 8.05; 95% CI, 5.67 to 11.44) and exposure to third-generation cephalosporins (OR, 2.07; 95% CI, 1.47 to 2.91). Our results suggest that the nosocomial occurrence of IRAB or ISAB is strongly related to an ICU stay, and IRAB occurrence may be favored by the selection pressure of imipenem.

Outcome of antibiotic therapy for third-generation cephalosporin-resistant Gram-negative bacteraemia: an analysis of 249 cases caused by Citrobacter, Enterobacter and Serratia species.

Two hundred and forty-nine patients with monomicrobial bacteraemia due to third-generation cephalosporin (TGC)-resistant Citrobacter freundii (42), E. aerogenes (23), E. cloacae (143), and Serratia marcescens (41) were analyzed for antibiotic therapy used and outcome. For isolates with resistance to any of the TGCs, all beta-lactams, except imipenem, were considered ineffective. Of 152 patients given appropriate treatment, the mortality rates were 10.9% for 128 patients given monotherapy and 25.0% for 24 patients given combination therapy (P=0.09). Of patients given monotherapy, there were no significant differences in mortality between imipenem, aminoglycoside, and ciprofloxacin treatment groups (P=0.57). Only shock was associated with mortality in multivariate analysis. In conclusion, for patients with TGC-resistant Gram-negative bacteraemia, no significant difference in outcome was observed between single antibiotic therapy groups or monotherapy and combination therapy groups.

Bacteraemia due to tribe Proteeae: a review of 132 cases during a decade (1991-2000).

To characterize the clinical features of bacteraemia due to tribe Proteeae, 132 cases among 130 patients from 1991 to 2000 were analysed. The organisms included the Proteus species in 63 cases (P. mirabilis in 41, P. penneri in 2 and P. vulgaris in 20), the Providencia species in 8 (P. rettgeri in 3 and P. stuartii 5) and Morganella morganii in 61. Morganella bacteraemia occurred more frequently in the hospital (70.5%). Biliary and hepatic diseases were predominant in cases with Morganella bacteraemia while cardiovascular, urological and neurological diseases were more common in cases with Proteus bacteraemia. Biliary drainage catheters had more frequently been placed in cases with Morganella bacteraemia (39.3%, p < 0.001), and urinary catheters more frequently in cases with Proteus bacteraemia (17.5%). Biliary infection was most common in cases with Morganella bacteraemia (49.2%), while urinary tract infection (UTI) was most common in cases with Proteus bacteraemia (47.6%). Mortality directly related to bacteraemia due to tribe Proteeae was 20.8% (22.6, 50.0 and 15.0% for Proteus, Providencia and Morganella bacteraemia, respectively). In conclusion, Morganella bacteraemia was most frequently associated with biliary infection, while Proteus bacteraemia was most frequently with UTI. Providencia bacteraemia was relatively uncommon and it can be associated with infections other than UTI.

Meningococcal disease in the republic of Korea army: incidence and serogroups determined by PCR.

This study was performed to determine the incidence and serogroups of meningococcal disease in the Korean Army. From August 2000 to July 2001, we identified prospective cases in the Korean Army. Meningococcal disease was confirmed by isolation of Neisseria meningitidis or detection of its antigen by latex agglutination from cerebrospinal fluid (CSF) or blood. Polymerase chain reactions (PCRs) were performed in the crgA gene to identify N. meningitidis regardless of its serogroup, and then in orf-2 (serogroup A) and siaD (serogroups B, C, Y, and W135) respectively for serogroup prediction. During the study period, twelve patients (four meningitis and eight septicaemia) were identified. The annual incidence was 2.2 per 100,000 (95% confidence interval, 1.3-3.8) among 550,000 private soldiers. Latex agglutinations were positive to A/C/Y/W135 polyvalent latex, but not to B latex in all patients. PCRs of crgA gene were positive in ten patients, whose samples (2 isolates from CSF, 2 CSFs, and 6 sera) were stored. In PCRs for serogroup prediction, one isolate was serogroup A, and one isolate and two sera were serogroup C. The need for meningococcal vaccination would be considered in the Korean Army through the cost-benefit analysis based on the result of this study.

The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults.

We studied an adenosine deaminase (ADA) activity in the cerebrospinal fluid (CSF) of 182 patients with meningitis. The patients were subdivided into four groups, (1) 36 cases of tuberculous meningitis; (2) 130 cases of viral or aseptic meningitis; (3) nine cases of bacterial meningitis; (4) seven cases of cryptococcal meningitis. Mean+/-S.D. ADA activity was 12.76+/-7.53 U/l in group 1; 2.58+/-2.37 U/l in group 2; 7.38+/-3.27 U/l in group 3; 7.42+/-4.38 U/l in group 4. Comparing the ADA activity in each group with the other groups, the difference is significant (P<0.001), except between groups 3 and 4. The sensitivity of the test for group 1 compared with group 2 was 0.83 and the specificity was 0.95 when a cut-off value of 7 U/l was used. When group 1 was compared with groups 3 and 4, the sensitivity was 0.58 and the specificity was 0.89 and 0.71 with groups 3 and 4, respectively, when a cut-off value of 10 U/l was used. Values >15 U/l were not observed in any of the non-tuberculous meningitis patients; therefore, ADA activity >15 U/l could be a strong indication of tuberculous meningitis. We conclude that a determination of CSF ADA can aid in the early differential diagnosis of tuberculous meningitis.

Serratia bacteremia in a large university hospital: trends in antibiotic resistance during 10 years and implications for antibiotic use.

OBJECTIVE: To identify antibiotic resistance trends and risk factors for resistance of Serratia species to third-generation cephalosporins. DESIGN: Retrospective survey of medical records. SETTING: A 2,200-bed, tertiary-care hospital. PATIENTS: One hundred twenty-two patients with Serratia bacteremia between January 1991 and June 2001. METHODS: Infectious disease physicians collected data from medical records regarding patient demographics, underlying disease or condition, portal of entry, microorganism, antibiogram, complications, antibiotics received, and outcome. RESULTS: Among 122 Serratia isolates, 117 (95.9%) were Serratia marcescens and 110 (90.2%) were of nosocomial origin. During the study period, the 122 isolates showed a high rate of resistance to third-generation cephalosporins (45.9%) and extended-spectrum penicillins (56.6%). The resistance rate to ciprofloxacin was 32.0%. The resistance rate to third-generation cephalosporins increased from 31.7% for 1991 to 1995 to 54.9% for 1996 to 1998 and 50.0% for 1999 to 2001. In the multivariate analysis, prior use of a second-generation cephalosporin (adjusted odds ratio [OR], 5.90; 95% confidence interval [CI90], 1.41 to 24.6; P = .015) or a third-generation cephalosporin (OR, 3.26; CI95, 1.20 to 8.87; P = .020) was a strong independent risk factor for resistance to third-generation cephalosporins. The overall case-fatality rate was 25.4% (Serratia bacteremia-related case-fatality rate, 13.1%). CONCLUSION: Prior use of a second- or third-generation cephalosporin was the most important risk factor for bacteremia with Serratia resistant to third-generation cephalosporins, suggesting the need for antibiotic control. The potential role of patient-to-patient spread could not be fully evaluated in this retrospective study.