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Background: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer., Methods: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia., Results: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia., Conclusions: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear., Objectives: We aimed to identify independent risk factors for IE in patients with VGS BSI., Methods: This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases., Results: Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14-32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03-12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96-1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13-0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01-0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87-14.68; P < 0.001)., Conclusions: Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia., (© 2024. The Author(s).)

A randomised controlled trial showed that rapid phenotypic antibiotic susceptibility testing (AST) with antimicrobial stewardship programme (ASP) increases the proportion of haematological patients with bacteraemia receiving optimal targeted therapy within 72 h of blood culture collection. This post-hoc analysis aimed to evaluate the effects of rapid phenotypic AST intervention in haematological patients at high risk of a poor outcome from bacteraemia. Haematological patients with bacteraemia (n = 116) were assigned randomly to a conventional AST group or a rapid AST group. The two outcome measures were the proportion of patients receiving optimal targeted therapy at 72 h post blood culture collection and the time to optimal targeted therapy; subgroup analysis was conducted based on baseline demographics (age, sex) and prognostic (Charlson comorbidity index, haematological treatment intensity, Pitt bacteraemia score, appropriateness of empirical antibiotic therapy and multidrug-resistant organism) indicators. The interaction effect between the intervention and subgroup factors was examined using regression model analysis. Age, sex, Charlson comorbidity index, haematological treatment intensity, Pitt bacteraemia score and appropriateness of empirical antibiotic therapy had no significant interaction effects on the proportion of patients receiving optimal targeted therapy (P = 0.129-0.826). However, infection by a multidrug-resistant organism did have a significant interaction effect (P = 0.042). Regarding time to optimal targeted therapy, there were no significant interaction effects between the intervention and subgroup factors (P = 0.156-0.848). In conclusion, rapid phenotypic AST with ASP intervention may accelerate early optimal targeted antimicrobial treatment of haematological patients, even those in high-risk subgroups with bacteraemia., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes., Methods: Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6-9 d, 10-13 d, 14-19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA., Results: TLR2 levels varied among 59 SAB patients. On days 2-5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2-5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNF-α ratios than the survivors did (P = 0.007)., Conclusion: TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted.

Background: Although the risk factors for positive follow-up blood cultures (FUBCs) in gram-negative bacteremia (GNB) have not been investigated extensively, FUBC has been routinely carried out in many acute care hospitals. We attempted to identify the risk factors and develop a predictive scoring model for positive FUBC in GNB cases., Methods: All adults with GNB in a tertiary care hospital were retrospectively identified during a 2-year period, and GNB cases were assigned to eradicable and non-eradicable groups based on whether removal of the source of infection was possible. We performed multivariate logistic analyses to identify risk factors for positive FUBC and built predictive scoring models accordingly., Results: Out of 1473 GNB cases, FUBCs were carried out in 1268 cases, and the results were positive in 122 cases. In case of eradicable source of infection, we assigned points according to the coefficients from the multivariate logistic regression analysis: Extended spectrum beta-lactamase-producing microorganism (+ 1 point), catheter-related bloodstream infection (+ 1), unfavorable treatment response (+ 1), quick sequential organ failure assessment score of 2 points or more (+ 1), administration of effective antibiotics (- 1), and adequate source control (- 2). In case of non-eradicable source of infection, the assigned points were end-stage renal disease on hemodialysis (+ 1), unfavorable treatment response (+ 1), and the administration of effective antibiotics (- 2). The areas under the curves were 0.861 (95% confidence interval [95CI] 0.806-0.916) and 0.792 (95CI, 0.724-0.861), respectively. When we applied a cut-off of 0, the specificities and negative predictive values (NPVs) in the eradicable and non-eradicable sources of infection groups were 95.6/92.6% and 95.5/95.0%, respectively., Conclusions: FUBC is commonly carried out in GNB cases, but the rate of positive results is less than 10%. In our simple predictive scoring model, zero scores-which were easily achieved following the administration of effective antibiotics and/or adequate source control in both groups-had high NPVs. We expect that the model reported herein will reduce the necessity for FUBCs in GNB cases.

The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n  = 995) than in patients with methicillin-susceptible SAB (MSSAB; n  = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P <  0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P <  0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality., (Copyright © 2019 American Society for Microbiology.)

Objectives: MALDI-TOF MS has been successfully used for empirical antibiotic selection. However, limited data are available regarding the usefulness of MALDI-TOF MS in common resistant organisms compared with rapid antimicrobial susceptibility testing (AST). We prospectively evaluated the usefulness of rapid AST, compared with MALDI-TOF MS, for optimal antibiotic selection by infectious disease (ID) physicians in patients with bacteraemia including polymicrobial infection., Methods: Three hundred and fifty-nine patients with positive blood culture were included for analysis. ID physicians prospectively decided on antibiotic regimens with consensus at each timepoint of receiving results of Gram stain, MALDI-TOF MS and rapid AST, the last of which was performed using QMAC-dRAST., Results: ID physicians with MALDI-TOF MS results chose optimal targeted antibiotics in 255 (71.0%) cases, with appropriate antibiotic selection in 303 (84.4%) cases. The proportion of optimal targeted antibiotic selection and appropriate antibiotic selection was significantly lower for resistant strains than for susceptible strains [62.5% versus 79.2% (P < 0.001) and 68.2% versus 100% (P < 0.001), respectively]. QMAC-dRAST results led to optimal antibiotic treatment in 95 (91.3%) of the 104 cases receiving non-optimal targeted antibiotics. Optimal targeted treatments based on QMAC-dRAST results were possible in 322 (98.2%) of the 328 cases with monobacterial infection and in 345 (96.1%) of the 359 cases with monobacterial and polymicrobial infection., Conclusions: MALDI-TOF MS has a high chance of failure in guiding ID physicians to optimal antibiotics, especially against resistant organisms. With increasingly common resistant organisms, rapid AST is needed to identify optimal targeted antibiotics early in bacteraemia., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: This study aimed to identify the predictors and build a prediction score for community-onset bloodstream infections (CO-BSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species., Methods: All CO-BSIs caused by E. coli and Klebsiella species from 2012 to 2015 were grouped into derivation (BSIs from 2012 to 2014) and validation (BSIs in 2015) cohorts. A prediction score was built using the coefficients of the multivariate logistic regression model from the derivation cohort., Results: The study included 886 CO-BSIs (594 and 292 in the derivation and validation cohorts, respectively). The independent predictors of CO-BSIs caused by ESBL-producing E. coli and Klebsiella species included: 1) identification of ESBL-producing microorganisms from any clinical culture within one year of admission, 2) beta-lactam or fluoroquinolone treatment within 30 days (with 2 or more courses within 90 days; with 1 course within 90 days), 3) hospitalization within one year, 4) the presence of an indwelling urinary catheter at the time of admission. The area under the curve (AUC) of the clinical prediction score was 0.72 (95% confidence interval [CI], 0.68-0.77). In the validation cohort, the AUC was 0.70 (95% CI, 0.63-0.77)., Conclusions: The results of this study suggest a simple and easy-to-use scoring system to predict CO-BSIs caused by ESBL-producing E. coli and Klebsiella species., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

The small-colony variant (SCV) phenotype of Staphylococcus aureus is associated with intracellular persistence and reduced antimicrobial susceptibility, which can lead to therapeutic failure. Since SCVs grow slowly and have a confusing morphology, the identification of infections due to SCV is difficult. We have identified SCVs in two patients who presented with persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia complicated by surgical site infections after cardiothoracic surgery. Nine blood isolates were collected from the two patients for species identification, antimicrobial susceptibility testing, and phenotypic and genotypic characterization. Colonies on Columbia blood agar were pinpoint, nonpigmented, nonhemolytic, and reverted to normal colonies after 48 hr of incubation on Schaedler agar. Auxotrophy assays revealed hemin dependence. Susceptibility to vancomycin (minimal inhibitory concentrations 1.0 μg/mL) was confirmed by E-test and broth microdilution test. All the isolates were identified as MRSA by multiplex polymerase chain reaction specific for the mecA, femA, and 16S rRNA genes, and all had the same genotype: Multilocus sequence typing ST5, SCCmec type II, agr type II, and spa type t2460. Moreover pulsed-field gel electrophoresis typing revealed that all nine isolates belonged to the same clone. Mutations in the relA gene were not found, and none of the isolates was identified as hVISA by population analysis profiling-AUC ratio. A high level of suspicion is required to detect SCVs, and although it is not common, the possibility of the SCV phenotype has to be considered in persistent S. aureus bacteremia.

Rapid identification of the microorganisms in patients with bacteremia may be useful in clinical practice. We evaluated the impact of the multiplex polymerase chain reaction (PCR) on appropriate antibiotic use for patients with gram-positive cocci cluster (GPCC) bacteremia. We divided the GPCC bacteremia cases into a pre-PCR group (2010-2011) and a post-PCR group (2012-2013). A total 664 cases were included in the pre-PCR group; and 570, in the post-PCR group. In methicillin-susceptible Staphylococcus aureus (MSSA) cases, optimal antibiotics were administered earlier in the post-PCR group (77.4h versus 42.6h, P=0.035). Although the proportions of glycopeptide exposure did not differ (54.7% versus 56.7%, P=0.799), the duration of exposure decreased (69.6h versus 30.7h, P=0.004). In methicillin-resistant S. aureus cases, the time to optimal antibiotics administration did not differ (45.4h versus 43.7h, P=0.275). Multiplex PCR test significantly improved the early initiation of optimal antibiotics in MSSA bacteremia and reduced the unnecessary glycopeptide exposure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

There have been few clinical studies on the association between the vancomycin 24-h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infections. To examine this association and to establish a suitable cut-off value for AUC24/MIC, a multicentre prospective observational study was conducted in patients with MRSA bacteraemia. Data were collected on all patients aged ≥18 years with MRSA bacteraemia treated with vancomycin for ≥72 h without dialysis. The MIC was determined by broth microdilution (BMD) and Etest. Treatment failure was defined as (i) 30-day mortality, (ii) persistent bacteraemia (≥7 days) and (iii) recurrence (≤30 days after completion of therapy). AUC24 was estimated by a Bayesian approach based on individual vancomycin concentrations. The AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by Classification and Regression Tree (CART) analysis. In total, 117 patients were enrolled, among which vancomycin treatment failure occurred in 38 (32.5%). In univariate analysis, high vancomycin MIC and low trough levels were unrelated to treatment outcomes. In the CART analysis, low vancomycin AUC24/MIC [<392.7 (BMD) and <397.2 (Etest)] was associated with treatment failure. In multivariate analysis, low AUC24/MIC was a risk factor for treatment failure [adjusted odds ratio (aOR)=3.50, 95% confidence interval (CI) 1.39-8.82 by BMD; aOR=5.61, 95% CI 2.07-15.24 by Etest]. AUC24/MIC is associated with vancomycin treatment outcomes in MRSA bacteraemia, and seeking individualised AUC24/MIC ratios above target (>400) may improve treatment outcomes., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Staphylococcal cassette chromosome mec element (SCCmec) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between SCCmec types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, including spa type, agr type, agr dysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmec type. Of 195 cases, 137 involved SCCmec types II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCCmec type IV (5/58) than that among types II/III (39/137, P = 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49; P = 0.002). Of the microbiological factors tested, agr dysfunction was the only significant factor that showed different positivity between the SCCmec types, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92; P = 0.003). SCCmec type IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate of agr dysfunction in SCCmec types II/III in South Korea., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Cefazolin is a common antibiotic for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Type A or C β-lactamase-producing MSSA frequently shows the cefazolin inoculum effect (CIE). However, the clinical implication of the CIE for MSSA bacteremia is obscure., Methods: MSSA bacteremic patients treated with cefazolin were included in a retrospective cohort study. The blaZ gene of the isolates was sequenced to identify the type of β-lactamase. The patients whose isolates showed a ≥4-fold increase in cefazolin, the minimal inhibitory concentration (MIC) at the high inoculum (∼5×10(7) CFU/ml), were assigned to the CIE-positive group and the remainder to the CIE-negative group. Treatment failure was assessed at 12 weeks after cefazolin was initiated., Results: A total of 113 MSSA bacteremic patients were included. Among the 113 isolates, 57.5% showed the CIE and 77.9% carried the blaZ gene; type A β-lactamase was 15.0% and type C was 40.7%. Persistent bacteremia was more common in the CIE-positive group (9% vs. 0%, p=0.04). Treatment failure rates were higher in the CIE-positive group with high bacterial burden infection, but the difference was not significant (48% vs. 25%, p=0.13). There was no significant difference of failure between groups with high-inoculum MIC ≥16 and ≤1 μg/ml (13% vs. 5%, p=0.31). In the multivariable analysis, underlying cardiovascular diseases, pneumonia, osteoarticular infections, and endocarditis were significant risk factors for treatment failure and the CIE was not significantly associated with treatment failure., Conclusion: The CIE might be associated with persistent bacteremia if cefazolin is used for MSSA bacteremia with a high burden of infections. However, the sites of infections are more important factors for the clinical outcome than the CIE.

Background: We estimated the nationwide burden of nosocomial S. aureus bloodstream infection (SA-BSI), a major cause of nosocomial infection, in South Korea., Methods: To evaluate the nationwide incidence of nosocomial SA-BSI, cases of SA-BSI were prospectively collected from 22 hospitals with over 500 beds over 4?months. Data on patient-days were obtained from a national health insurance database containing the claims data for all healthcare facilities in South Korea. The additional cost of SA-BSI was estimated through a matched case?control study. The economic burden was calculated from the sum of the medical costs, the costs of caregiving and loss of productivity., Results: Three hundred and thirty nine cases of nosocomial SA-BSI were included in the study: 254 cases of methicillin-resistant SA-BSI (MRSA-BSI) and 85 cases of methicillin-susceptible SA-BSI (MSSA-BSI). Death related to BSI occurred in 81 cases (31.9%) of MRSA-BSI and 12 cases (14.1%) of MSSA-BSI. The estimated incidence of nosocomial MRSA-BSI was 0.12/1,000 patient-days and that of nosocomial MSSA-BSI, 0.04/1,000 patient-days. The estimated annual cases of nosocomial BSI were 2,946 for MRSA and 986 for MSSA in South Korea. The additional economic burden per case of nosocomial SA-BSI was US $20,494 for MRSA-BSI and $6,914 for MSSA-BSI. Total additional annual cost of nosocomial SA-BSI was $67,192,559., Conclusion: In view of the burden of nosocomial SA-BSI, a national strategy for reducing nosocomial SA-BSI is urgently needed in South Korea.

There have been few clinical studies on the association between the 24-h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infections. Patients with MRSA bacteraemia between July 2009 and January 2012 were analysed retrospectively. All adult patients treated with vancomycin for ≥72 h without dialysis were included. The MIC was determined by Etest and broth microdilution (BMD). Initial steady-state AUC24 was estimated using a Bayesian model, and the AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by classification and regression tree (CART) analysis. In total, 76 patients were enrolled; vancomycin treatment failure occurred in 20 patients (26.3%). Catheter-related infection was the most frequent (35.5%), followed by surgical site infection (26.3%), whilst 25 (32.9%) had complicated infections. In univariate analysis, decreased MRSA vancomycin susceptibility (MIC≥1.5 mg/L) and vancomycin trough levels (15-20 mg/L) were not associated with treatment outcomes. In the CART analysis, low initial vancomycin AUC24/MIC (<430 by Etest; <398.5 by BMD) was associated with a higher treatment failure rate (50.0% vs. 25.0%, P=0.039 by Etest; 45.0% vs. 23.2%; P=0.065 by BMD). In multivariate analysis, low initial vancomycin AUC24/MIC was a significant risk factor for treatment failure [adjusted odds ratio (aOR)=4.39, 95% confidence interval (CI), 1.26-15.35 by Etest; aOR=3.73, 95% CI 1.10-12.61 by BMD]. In MRSA bacteraemia, a low initial vancomycin AUC24/MIC is an independent risk factor for vancomycin treatment failure., (Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: The need for mandatory confirmation of negative conversion in Klebsiella pneumoniae bacteremia (KpB) has not been adequately addressed. We conducted a retrospective case-control study of adult patients with KpB over a 5-year period in two tertiary-care hospitals to determine the risk factors for persistent bacteremia and to reevaluate the necessity of follow-up blood culture in KpB., Methods: Persistent KpB is defined as the finding of K. pneumoniae in more than two separate blood-culture samples for longer than a two-day period in a single episode. The case- and control-groups were patients with persistent and non-persistent KpB, respectively, and they were matched 1-to-3 according to age and gender., Results: Among 1068 KpB episodes analyzed after excluding polymicrobial infection and repeated KpB, follow-up blood cultures were performed in 862 cases (80.7%), 62 of which (7.2%) were persistent. Independent risk factors for persistence were intra-abdominal infection, higher Charlson's comorbidity weighted index score, prior solid organ transplantation, and unfavorable treatment response, which was defined as positivity for at least two parameters among fever, leukocytosis, and no decrease of C-reactive protein on the second day after initial culture. A proposed scoring system using four variables, namely, intra-abdominal infection, nosocomial KpB, fever and lack of C-reactive protein decrease, the last two being assessed on the second day after the initial blood culture, showed that only 4.9% of the patients with no risk factors or with only intra-abdominal infection had persistent KpB., Conclusions: Though persistent KpB is uncommon, follow-up blood culture was performed in as many as 80% of the cases in this study. A more careful clinical assessment is warranted to reduce the cost and patient inconvenience involved in follow-up blood culture.

Background: This study was performed to detect risk factors for Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis., Methods: A retrospective case-control study was designed to identify risk factors for P. aeruginosa bacteremia in cirrhotic patients. The cases were cirrhotic patients with P. aeruginosa bacteremia and the controls were cirrhotic patients with Enterobacteriaceae bacteremia., Results: Sixty-one cases and the same number of controls were enrolled. In a multivariate analysis, younger age {adjusted odds ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were associated with P. aeruginosa bacteremia. In the case group the frequency of appropriate initial antibiotic regimens was considerably lower than in the control group: 29.5% vs. 65.6% (P <0.01). However, thirty day mortality did not differ significantly between cases and controls (19.7% vs. 24.6%)., Conclusions: Nosocomial acquisition, preexisting biliary disease, and recent use of immunosuppressive agents are strong predictive factors for P. aeruginosa bacteremia in cirrhotic patients.

Although tigecycline is considered one of the few therapeutic options for carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia, its role in the treatment of CRAB bacteraemia remains unclear. We describe the clinical outcomes of 9 patients who received tigecycline for CRAB bacteraemia. Although all CRAB blood isolates were susceptible to tigecycline, 5 (56%) deaths were related to CRAB bacteraemia and 1 case of breakthrough CRAB bacteraemia was observed during tigecycline therapy. Clinical outcomes of tigecycline therapy may be poor in patients with tigecycline-susceptible CRAB bacteraemia, although multiple factors including delayed treatment could contribute to the poor outcomes.

Background: Healthcare-associated (HCA) infection has emerged as a new epidemiological category. The aim of this study was to evaluate the impact of HCA infection on mortality in community-onset Klebsiella pneumoniae bloodstream infection (KpBSI)., Methods: We conducted a retrospective study in two tertiary-care hospitals over a 6-year period. All adult patients with KpBSI within 48 hours of admission were enrolled. We compared the clinical characteristics of HCA and community-acquired (CA) infection, and analyzed risk factors for mortality in patients with community-onset KpBSI., Results: Of 553 patients with community-onset KpBSI, 313 (57%) were classified as HCA- KpBSI and 240 (43%) as CA-KpBSI. In patients with HCA-KpBSI, the severity of the underlying diseases was higher than in patients with CA-KpBSI. Overall the most common site of infection was the pancreatobiliary tract. Liver abscess was more common in CA-KpBSI, whereas peritonitis and primary bacteremia were more common in HCA-KpBSI. Isolates not susceptible to extended-spectrum cephalosporin were more common in HCA- KpBSI than in CA-KpBSI (9% [29/313] vs. 3% [8/240]; p = 0.006). Overall 30-day mortality rate was significantly higher in HCA-KpBSI than in CA-KpBSI (22% [70/313] vs. 11% [27/240]; p = 0.001). In multivariate analysis, high Charlson's weighted index of co-morbidity, high Pitt bacteremia score, neutropenia, polymicrobial infection and inappropriate empirical antimicrobial therapy were significant risk factors for 30-day mortality., Conclusions: HCA-KpBSI in community-onset KpBSI has distinctive characteristics and has a poorer prognosis than CA-KpBSI, but HCA infection was not an independent risk factor for 30-day mortality.

About 20% of methicillin-susceptible Staphylococcus aureus (MSSA) isolates have a substantial inoculum effect with cefazolin, suggesting that cefazolin treatment may be associated with clinical failure for serious MSSA infections. There are no well-matched controlled studies comparing cefazolin with nafcillin for the treatment of MSSA bacteremia. A retrospective propensity-score-matched case-control study was performed from 2004 to 2009 in a tertiary care hospital where nafcillin was unavailable from August 2004 to August 2006. The cefazolin group (n = 49) included MSSA-bacteremic patients treated with cefazolin during the period of nafcillin unavailability, while the nafcillin group (n = 84) comprised those treated with nafcillin. Treatment failure was defined as a composite outcome of a change of antibiotics due to clinical failure, relapse, and mortality. Of 133 patients, 41 patients from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment failure rates were not significantly different at 4 or 12 weeks (10% [4/41] versus 10% [4/41] at 4 weeks [P > 0.99] and 15% [6/41] versus 15% [6/41] at 12 weeks [P > 0.99]). Cefazolin treatment was interrupted less frequently than nafcillin treatment due to drug adverse events (0% versus 17%; P = 0.02). Cefazolin had clinical efficacy similar to that of nafcillin and was more tolerable than nafcillin for the treatment of MSSA bacteremia.

High-level gentamicin resistance (HLGR) in enterococci has increased since the 1980s, but the clinical significance of the resistance and its impact on outcome have not been established. One hundred and thirty-six patients with bacteremia caused by enterococci with HLGR (HLGR group) were compared with 79 patients with bacteremia caused by enterococci without HLGR (non-HLGR group). Hematologic malignancy, neutropenia, Enterococcus faecium infection, nosocomial infection and monomicrobial bacteremia were more common in the HLGR group than the non-HLGR group, and APACHE II scores were also higher (P<0.05, in each case). Neutropenia, monomicrobial infection, stay in intensive care at culture, and use of 3rd generation cephalosporin, were independent risk factors for acquisition of HLGR enterococcal bacteremia. Fourteen-day and 30-day mortalities were higher in the HLGR group than the non-HLGR group in univariate analysis (37% vs. 15%, P=0.001; 50% vs. 22%, P<0.001). However, HLGR was not an independent risk factor for mortality due to enterococcal bacteremia in multivariate analysis. Therefore, HLGR enterococcal bacteremia is associated with more severe comorbid conditions and higher mortality than non-HLGR enterococcal bacteremia but the HLGR itself does not contribute significantly to mortality.

Background: Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high mortality rates, but no treatment strategy has yet been established. We performed this study to evaluate the efficacy of linezolid with or without carbapenem in salvage treatment for persistent MRSA bacteremia., Methods: All adult patients with persistent MRSA bacteremia for 7 days from January 2006 through March 2008 who were treated at Seoul National University Hospital were studied. The results of linezolid salvage therapy with or without carbapenem were compared with those of salvage therapy with vancomycin plus aminoglycosides or rifampicin., Results: Thirty-five patients with persistent MRSA bacteremia were studied. The early microbiological response (ie, negative results for follow-up blood culture within 72 hours) was significantly higher in the linezolid-based salvage therapy group than the comparison group (75% vs 17%; P =.006). Adding aminoglycosides or rifampicin to vancomycin was not successful in treating any of the patients, whereas linezolid-based therapy gave an 88% salvage success rate P =.001). The S. aureus-related mortality rate was lower for patients treated with a linezolid salvage regimen than for patients continually treated with a vancomycin-based regimen (13% vs 53%; P =.030)., Conclusions: Linezolid-based salvage therapy effectively eradicated S. aureus from the blood for patients with persistent MRSA bacteremia. The salvage success rate was higher for linezolid therapy than for vancomycin-based combination therapy.

Limited data on the clinical outcome of vancomycin treatment compared with that of beta-lactam treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B) are available. We used different and complementary approaches: (i) a retrospective cohort study using a propensity score to adjust for confounding by treatment assignment and (ii) a matched case-control study. Of all patients with S. aureus bacteremia (SAB) in two university-affiliated hospitals over a 7-year period, 294 patients with MSSA-B were enrolled in the cohort study. The cases for the case-control study were defined as patients who received vancomycin treatment for MSSA-B; the controls, who were patients that received beta-lactam treatment for MSSA-B, were selected at a 1:2 (case:control) ratio according to the objective matching scoring system and the propensity score system. In the cohort study, SAB-related mortality in patients with vancomycin treatment (37%, 10/27) was significantly higher than that in those with beta-lactam treatment (18%, 47/267) (P = 0.02). In addition, multivariate analysis revealed that vancomycin treatment was associated with SAB-related mortality when independent predictors for SAB-related mortality and propensity score were considered (adjusted odds ratio of 3.3, 95% confidence interval of 1.2 to 9.5). In the case-control study using the objective matching scoring system and the propensity score system, SAB-related mortality in case patients was 37% (10/27) and in control patients 11% (6/54) (P < 0.01). Our data suggest that vancomycin is inferior to beta-lactam in the treatment of MSSA-B.

Invasion of vascular endothelial cells is thought to be a critical step in the development of metastatic infections in patients with Staphylococcus aureus bacteraemia. This study was designed to evaluate the association between the ability to invade endothelial cells and metastatic infection by S. aureus. Patients with metastatic infection were identified among those with community-acquired S. aureus bacteraemia in a tertiary referral hospital. Patients with simple bacteraemia caused by S. aureus over the same period served as the control group. The ability of each clinical isolate to invade endothelial cells was evaluated by counting the number of intracellular organisms 1 h after inoculation onto human umbilical vein endothelial cells in vitro. The cytotoxic activity of intracellular S. aureus was determined 24 h after internalization, and expressed as the percentage of cells killed. The clinical isolates varied in invasiveness and cytotoxicity. The median invasiveness, relative to S. aureus reference strain ATCC 29213, was 145 % in the cases (n=10) [interquartile range (IQR) 103-160] and 153 % (IQR 111-173) in the controls (n=11; P=0.44). The median cytotoxicity was 59.4 % (IQR 47-68) in the cases and 65.2 % (IQR 50-74) in the controls (P=0.44). Differences in the ability of S. aureus to invade and destroy vascular endothelial cells in vitro were not associated with the development of metastatic complications in patients with S. aureus bacteraemia. This implies that the invasiveness and toxicity of S. aureus for endothelial cells may not be major determinants of metastatic infection.

We conducted this study to compare clinical features, outcomes, and clinical implication of antimicrobial resistance in Klebsiella pneumoniae bacteremia acquired as community vs. nosocomial infection. A total of 377 patients with K. pneumoniae bacteremia (191 community-acquired and 186 nosocomial) were retrospectively analyzed. Neoplastic diseases (hematologic malignancy and solid tumor, 56%) were the most commonly associated conditions in patients with nosocomial bacteremia, whereas chronic liver disease (35%) and diabetes mellitus (20%) were the most commonly associated conditions in patients with community-acquired bacteremia. Bacteremic liver abscess occurred almost exclusively in patients with community-acquired infection. The overall 30-day mortality was 24% (91/377), and the mortality of nosocomial bacteremia was significantly higher than that of community-acquired bacteremia (32% vs. 16%, p<0.001). Of all community-acquired and nosocomial isolates, 4% and 33%, respectively, were extended-spectrum cephalosporin (ESC)-resistant, and 4% and 21%, respectively, were ciprofloxacin (CIP)-resistant. In nosocomial infections, prior uses of ESC and CIP were found to be independent risk factors for ESC and CIP resistance, respectively. Significant differences were identified between community-acquired and nosocomial K. pneumoniae bacteremia, and the mortality of nosocomial infections was more than twice than that of community-acquired infections. Antimicrobial resistance was a widespread nosocomial problem and also identified in community-acquired infections.

We describe a case of bacteremia due to imipenem-susceptible Shewanella algae. Despite treatment with imipenem, the patient developed a spinal epidural abscess, from which imipenem-resistant S. algae was isolated. The development of resistance should be monitored when S. algae infection is treated with imipenem, even though the strain is initially susceptible to imipenem.

To assess the effect of liver dysfunction on the production of C-reactive protein (CRP), CRP levels were evaluated in patients with Escherichia coli bacteremia with or without liver cirrhosis (LC). Thirty patients of each kind were selected as case and control groups, respectively. A matched control of 30 LC patients without acute infection was also included. In the patients with E. coli bacteremia, median CRP was 6.2 mg/dL (range 0.2-22.1) in the LC patients and 14.6 mg/dL (range 5.8-39.6) in the patients without liver dysfunction (P < 0.001). In the advanced LC patients in Child-Pugh class C, median CRP was 5.0 mg/dL (range 0.2-12.1) in patients with E. coli bacteremia and 0.5 mg/dL (range 0.1-1.2) in patients without acute infection (P < 0.001). Our data suggest that, although CRP levels are reduced in response to acute infection, production is nevertheless maintained even in patients with advanced liver dysfunction.

This study was conducted to evaluate risk factors for antimicrobial resistance and influence of resistance on mortality in Pseudomonas aeruginosa bacteremia. Data on 190 patients with P. aeruginosa bacteremia were analyzed retrospectively. Antimicrobial resistance to antipseudomonal antibiotics was evaluated. The main outcome measure was 30-day mortality. In P. aeruginosa bacteremia, resistance rates to piperacillin (PIP), ceftazidime (CAZ), ciprofloxacin (CIP), and imipenem (IPM) were 29 (56/190), 19 (36/190), 17 (32/190) and 15% (28/190), respectively. Prior uses of fluoroquinolones or carbapenems were independent risk factors for resistance to CIP and IPM, and prior use of extended-spectrum cephalosporins was a risk factor for PIP-R. An indwelling urinary catheter was a risk factor for PIP-R, CAZ-R, and CIP-R. An invasive procedure was a risk factor for CIP-R and IPM-R. The 30-day mortality rate was 44% (33/75) in patients infected by strains resistant to any of the antipseudomonal antibiotics, but 33.9% (39/115) in those by strains susceptible to all antipseudomonal antibiotics (p = 0.161). Among patients with bloodstream infection due to antimicrobial-resistant P. aeruginosa, those infected by IPM-R strains had the highest mortality (IPM-R, 53.6% vs. CAZ-R, 47.2% vs. CIP-R 46.9%, PIP-R, 39.3%). In this study regarding P. aeruginosa bacteremia, prior uses of fluoroquinolones, carbapenems, or extended-spectrum cephalosporins, a prior invasive procedure, and an indwelling urinary catheter were found to be associated with antimicrobial resistance. The patients with bloodstream infection caused by antimicrobial-resistant P. aeruginosa, especially to imipenem, had a tendency toward higher mortality than those infected by susceptible strains.

The marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern, as patients infected by those isolates might initially receive antibiotics that are inactive against the responsible pathogens. To evaluate the effect of inappropriate initial antimicrobial therapy on survival, a total of 286 patients with antibiotic-resistant gram-negative bacteremia, 61 patients with Escherichia coli bacteremia, 65 with Klebsiella pneumoniae bacteremia, 74 with Pseudomonas aeruginosa bacteremia, and 86 with Enterobacter bacteremia, were analyzed retrospectively. If a patient received at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture collection, the initial antimicrobial therapy was considered to have been appropriate. High-risk sources of bacteremia were defined as the lung, peritoneum, or an unknown source. The main outcome measure was 30-day mortality. Of the 286 patients, 135 (47.2%) received appropriate initial empirical antimicrobial therapy, and the remaining 151 (52.8%) patients received inappropriate therapy. The adequately treated group had a 27.4% mortality rate, whereas the inadequately treated group had a 38.4% mortality rate (P = 0.049). Multivariate analysis showed that the significant independent risk factors of mortality were presentation with septic shock, a high-risk source of bacteremia, P. aeruginosa infection, and an increasing APACHE II score. In the subgroup of patients (n = 132) with a high-risk source of bacteremia, inappropriate initial antimicrobial therapy was independently associated with increased mortality (odds ratio, 3.64; 95% confidence interval, 1.13 to 11.72; P = 0.030). Our data suggest that inappropriate initial antimicrobial therapy is associated with adverse outcome in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia.

This study was conducted to evaluate risk factors for mortality and treatment outcome of bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production in stored K. pneumoniae and E. coli blood isolates from Jan 1998 to Dec 2002 was phenotypically determined according to NCCLS guidelines and/or the double-disk synergy test. A total of 133 patients with ESBL-EK bacteremia, including 66 patients with ESBL-producing K. pneumoniae and 67 with ESBL-producing E. coli, were enrolled. The overall 30-day mortality rate was 25.6% (34 of 133). Independent risk factors for mortality were severe sepsis, peritonitis, neutropenia, increasing Acute Physiology and Chronic Health Evaluation II score, and administration of broad-spectrum cephalosporin as definitive antimicrobial therapy (P < 0.05 for each of these risk factors). In 117 of the 133 patients, excluding 16 patients who died within 3 days after blood culture sample acquisition, the 30-day mortality rates according to definitive antibiotics were as follows: carbapenem, 12.9% (8 of 62); ciprofloxacin, 10.3% (3 of 29); and others, such as cephalosporin or an aminoglycoside, 26.9% (7 of 26). When patients who received appropriate definitive antibiotics, such as carbapenem or ciprofloxacin, were evaluated, mortality in patients receiving inappropriate empirical antimicrobial therapy was found not to be significantly higher than mortality in those receiving appropriate empirical antimicrobial therapy (18.9 versus 15.5%; P = 0.666). Carbapenem and ciprofloxacin were the most effective antibiotics in antimicrobial therapy for ESBL-EK bacteremia. A delay in appropriate definitive antimicrobial therapy was not associated with higher mortality if antimicrobial therapy was adjusted appropriately according to the susceptibility results. Our data suggest that more prudent use of carbapenem as empirical antibiotic may be reasonable.

Cases of bacteremia caused by AmpC-type-beta-lactamase-producing Klebsiella pneumoniae isolates were retrospectively studied to determine the epidemiologic features and clinical outcomes of bloodstream infections. Among 389 blood isolates recovered from 1998 to 2002, 65 isolates (16.7%) were found to be extended-spectrum beta-lactamase (ESBL) or AmpC beta-lactamase producers. The beta-lactamases from 61 of the 65 isolates were characterized; 28 of 61 isolates produced AmpC-type enzymes (14 isolates each produced DHA-1 and CMY-1-like enzymes), 32 isolates produced TEM or SHV-related ESBLs, and 1 isolate produced a CTX-M-14-like enzyme. To compare the clinical features and outcomes of bloodstream infections caused by AmpC producers with those caused by TEM- or SHV-related ESBL producers, 27 patients infected with isolates producing AmpC-type enzymes (AmpC group) and 25 patients infected with isolates producing TEM- or SHV-related enzymes (ESBL group) were analyzed. There was no significant difference between the AmpC and the ESBL groups in terms of risk factors. When the initial response was assessed at 72 h after antimicrobial therapy, the treatment failure rate for the AmpC group was 51.9% (14 of 27 patients) and the 7- and 30-day mortality rates were 14.8 and 29.6%, respectively, which were similar to those for the ESBL group. When the mortality rate for the patients who received extended-spectrum cephalosporins as definitive treatment was assessed, all four patients in the DHA-1 group and one of three patients in the CMY-1-like group died. In summary, the prevalence of AmpC enzyme-producing K. pneumoniae was high at the Seoul National University Hospital, and the clinical features and outcomes for the patients infected with AmpC-producing organisms were similar to those for the patients infected with TEM- or SHV-related ESBL producers.

Objective: To evaluate risk factors and treatment outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP)., Design: Retrospective case-control study. Stored blood isolates of K. pneumoniae were tested for ESBL production by NCCLS guidelines, double-disk synergy test, or both., Setting: A 1,500-bed, tertiary-care university hospital and referral center., Patients: Sixty case-patients with bacteremia due to ESB-KP were compared with 60 matched control-patients with non-ESBL-KP., Results: There were no significant differences in age, gender, APACHE II score, or underlying diseases between the groups. Independent risk factors for infections caused by ESBL-KP were urinary catheterization, invasive procedure within the previous 72 hours, and an increasing number of antibiotics administered within the previous 30 days. Complete response rate, evaluated 72 hours after initial antimicrobial therapy, was higher among control-patients (13.3% vs 36.7%; P = .003). Treatment failure rate was higher among case-patients (35.0% vs 15%; P = .011). Overall 30-day mortality rate was 30% for case-patients and 28.3% for control-patients (P = .841). Case-patients who received imipenem or ciprofloxacin as a definitive antibiotic had 10.5% mortality. The mortality rate for initially ineffective therapy was no higher than that for initially effective therapy (9.1% vs 11.1%; P = 1.000), but statistical power was low for evaluating mortality in the absence of septic shock., Conclusion: For K. pneumoniae bacteremia, patients with ESBL-KP had a higher initial treatment failure rate but did not have higher mortality if antimicrobial therapy was appropriately adjusted in this study with limited statistical power.

Background: Enterobacter species have become increasingly important nosocomial pathogens. However, resistance to cephalosporins often complicates the treatment of Enterobacter infection. This study was conducted to evaluate the predictors of mortality and the impact of cephalosporin resistance on outcome in patients with Enterobacter bacteremia., Methods: A total of 183 patients with Enterobacter bacteremia were retrospectively analyzed. Broad-spectrum cephalosporin resistance was defined as in vitro resistance to cefotaxime or ceftazidime. The main outcome measure was the 30-day mortality rate., Results: Of 183 patients, 86 (47%) had bacteremia caused by broad-spectrum cephalosporin-resistant Enterobacter species, and their infections were classified as resistant. The 30-day mortality rate of patients with resistant infections (the resistant group) was significantly higher than that of patients with susceptible infections (the susceptible group) (33.7% vs. 18.6%; P=.021). When the 30-day mortality rates were compared according to the primary sites of infection and underlying conditions, the 30-day mortality rates of the resistant group were significantly higher than those of the susceptible group, in patients with an unknown primary site of infection, or in patients with septic shock. Multivariate analysis showed that broad-spectrum cephalosporin resistance was one of the independent risk factors associated with 30-day mortality (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.01-13.52; P=.049). Presentation with septic shock and an increasing Acute Physiology and Chronic Health Evaluation II score were also independent risk factors for mortality (OR, 59.91 [95% CI, 14.93-240.15; P<.001] and 1.52 [95% CI, 1.24-1.86; P<.001], respectively)., Conclusions: Broad-spectrum cephalosporin resistance adversely affects the outcome of patients with Enterobacter bacteremia, especially those with an unknown primary site of infection and those with septic shock.

Background: This study was conducted to evaluate the risk factors for infection and clinical outcomes of bacteremic spontaneous bacterial peritonitis (SBP) due to ESBL-producing E. coli and K. pneumoniae, in patients with advanced liver cirrhosis., Methods: The ESBL production was determined by NCCLS guidelines and/or double-disk synergy tests, on stored E. coil and K. pneumoniae blood isolates collected between 1998 and 2002. Of the patients with advanced liver cirrhosis, 15 case patients, with SBP due to ESBL-producers, were compared with 30 matched controls, with SBP due to non-ESBL-producers., Results: There were no significant differences in age, sex, Child-Pugh scores, or APACHE II scores between the two groups. Significant factors associated with infection by ESBL-producing organisms, according to univariate analysis, were: ICU care, indwelling urinary catheter, central venous catheterization, an invasive procedure within the previous 72 hours, and prior use of antibiotics within the previous 30 days. When assessing the clinical response at 72 hours after the initial antimicrobial therapy, the treatment failure rate was significantly higher in the ESBL group (73.3% vs. 16.7%, p<0.001). Also, overall 30-day mortality rates were 60% (9/15) in the ESBL groups and 23.3% (7/30) in the control group (p=0.015)., Conclusion: Among patients with advanced liver cirrhosis, bacteremic SBP due to ESBL-producing E. coil and K. pneumoniae was associated with adverse outcomes, and significantly higher mortality.

Objective: To determine the impact of delayed treatment of methicillin-resistant Staphylococcus aureus bacteraemia (MRSA bacteraemia) on mortality., Patients and Methods: We used two different and complementary approaches: a retrospective cohort study and a matched case-control study. Of the total of all patients with S. aureus bacteraemia in a tertiary hospital over a 4 year period, 127 patients with MRSA bacteraemia were enrolled in the cohort study. The cases for the case-control study were defined as patients who received appropriate empirical treatment for MRSA bacteraemia; the controls, who were patients who received inappropriate empirical treatment for MRSA bacteraemia, were selected according to the matching variables of age, sex, severity of underlying illness, classification of main underlying disease and prior hospital stay. On the 14-point matching scale that was used to select the best controls, the average score (+/-S.D.) of the 30 controls was 11.2 (+/-2.0)., Results: In the cohort study, the difference in S. aureus bacteraemia-related mortality between appropriate (30%, 9/30) and inappropriate (39%, 38/97) empirical treatment was not significant (P=0.36). In addition, multivariate analysis did not indicate that inappropriate empirical treatment was associated with mortality when independent predictors for mortality were considered (adjusted OR 1.1, 95% CI 0.4-3.1). In the case-control study, S. aureus bacteraemia-related mortality in case patients was 30% (9/30) and in control patients 33% (10/30) (P>0.99, McNemar's test). In four of the nine discordant pairs, the case patients died whereas the control patients lived., Conclusions: Our data suggest that an initial delay of 2 days in the use of appropriate antibiotics, especially of vancomycin or other glycopeptides, before the preliminary microbiological report may not adversely affect the outcome in patients with MRSA bacteraemia.

The present study was conducted to identify risk factors for ciprofloxacin resistance in bloodstream infections due to extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production was determined in stored E. coli and K. pneumoniae blood isolates from January, 1998, to December, 2002, by National Committee for Clinical Laboratory Standards (NCCLS) guidelines and/or double-disk synergy test. Antimicrobial susceptibility was determined by the disk diffusion test method. A total of 133 patients with ESBL-EK bacteremia were analyzed retrospectively. A total of 80 (60.2%) patients experienced bacteremia due to strains resistant to ciprofloxacin. There were no significant differences in age, sex, and APACHE II score between the ciprofloxacin-resistant group (CIP-R) and-susceptible group (CIPS). The most common primary site of infection in CIP-R was pancreaticobiliary tract infection (46/80, 57.5%) and that in CIP-S was unknown primary site (23/53, 43.4%). Independent risk factors for ciprofloxacin resistance were: prior use of fluoroquinolones (OR, 5.53; 95% CI, 1.56-25.42, p = 0.032), indwelling urinary catheter (OR, 3.68; 95% CI, 1.27-10.67, p = 0.017), and invasive procedure within 72 hr prior to bacteremia (OR, 4.03; 95% CI, 1.44-11.25, p = 0.008). Our data suggest that strategies designed to reduce the ciprofloxacin resistance rate in ESBL-EK strains should focus on limiting the use of fluoroquinolones and minimizing invasive procedures, including insertion of a urinary catheter.

Objective: To evaluate the outcome of attempted Hickman catheter salvage in neutropenic cancer patients with Staphylococcus aureus bacteremia who were not using antibiotic lock therapy., Design: Retrospective cohort study., Setting: A university-affiliated, tertiary-care hospital with 1,500 beds for adult patients., Patients: All neutropenic cancer patients who had a Hickman catheter and S. aureus bacteremia (32 episodes in 29 patients) between January 1998 and March 2002., Methods: Salvage attempts were defined as cases where the Hickman catheter was not removed until we obtained the results of follow-up blood cultures performed 48 to 72 hours after starting treatment with antistaphylococcal antibiotics. Salvage was considered to be successful if the Hickman catheter was still in place 3 months later without recurrent bacteremia or death., Results: Catheter salvage was attempted in 24 (75%) of the 32 episodes. Of the salvage attempts, the success rate was 50% (12 of 24). Salvage attempts were successful in 14% (1 of 7) of the episodes with positive follow-up blood cultures, and in 65% (11 of 17) of those with negative follow-up blood cultures (P = .07). If the analysis is confined to cases with no external signs of catheter infection, salvage attempts were successful in 14% (1 of 7) of the episodes with positive follow-up blood cultures and in 80% (8 of 10) of those with negative follow-up blood cultures (P = .02)., Conclusion: In neutropenic cancer patients with S. aureus bacteremia, attempted catheter salvage without antibiotic lock therapy was successful in 50% of the cases.

Among the nosocomial pathogens, Pseudomonas aeruginosa is recognized as a major cause of morbidity and mortality. Data on 136 patients with P. aeruginosa bacteremia were retrospectively analyzed to evaluate risk factors for mortality. The median age of the patients was 55 years (range, 15-85 years), 78.7% of the cases were hospital-acquired, and the 30-day mortality rate was 39% (53 of 136 patients). Multivariate analysis demonstrated that risk factors for mortality included severe sepsis, pneumonia, delay in starting effective antimicrobial therapy, and an increasing APACHE II score (all P values <.05). In 123 of the 136 patients (excluding 13 patients treated with inadequate definitive antibiotics), 30-day mortality was 27.7% (13 of 47 patients) in the group of patients who received initially effective empirical antimicrobial therapy, and 43.4% (33 of 76) in the group of patients who received delayed effective antimicrobial therapy (P=.079). There was a trend toward higher mortality as the length of delay increased. Delay in starting effective antimicrobial therapy for P. aeruginosa bacteremia tended to be associated with higher mortality.

To determine the outcome of Staphylococcus aureus bacteremia (SAB) on mortality, including the impact of methicillin resistance and an initial delay (< or =48 h) of appropriate antibiotics, a retrospective cohort study including 238 patients with SAB was performed. By logistic regression, noneradicable or noneradicated foci, underlying cirrhosis, and cancer were found to be independent predictors of mortality. In patients with eradicable foci, there were no significant differences in the associated mortality rate between methicillin-resistant SAB (11%) and methicillin-susceptible SAB (13%), and between inappropriate (13%) and appropriate (10%) empirical therapy, respectively (P=.79 and P=.78, respectively). By logistic regression, it was found that, in the subgroup of patients with noneradicable foci, underlying cirrhosis (odds ratio [OR], 3.1) and methicillin-resistant SAB (OR, 2.4) were independently associated with mortality.

Background Universal follow-up blood culture (FUBC) in gram-negative bacteremia (GNB) is not recommended, but it has been routinely conducted in many acute-care hospitals. In contrast with Staphylococcus aureus bacteremia , risk factors for positive FUBC in GNB have not been well investigated. Therefore, we tried to identify the risk factors for and develop predictive scores of positive FUBC. Methods All adults (≥18 years-old) with GNB were identified in a tertiary-care hospital during the 2-year period, retrospectively. Death within 2 days of GNB and polymicrobial infection with gram-positive bacteria or fungus were excluded. GNB were classified into eradicable and non-eradicable source of infection groups, according to the possibility of source removal. We performed multivariate analyses for identifying risk factors for positive FUBC and built prediction scores using the coefficients of the multivariate logistic regression models. Results Of total 1,473 GNB, FUBC was drawn in 1,268 (86%) patients and 122 (9.6%) had positive results. In patients with eradicable source of infection, ESBL-producing microorganism, catheter-related bloodstream infection, unfavorable treatment response, and quick sequential organ failure assessment (qSOFA) score (≥2) were associated. On the other hand, administration of effective antibiotics and adequate source control were negatively associated with positive FUBC. In non-eradicable source of infection, end-stage renal disease on hemodialysis, and unfavorable treatment response were related to positive FUBC and administration of effective antibiotics was negatively associated (Table 1). When we built prediction scores according to the coefficients, the areas under the curves were 0.864 (95% confidence interval [CI95] 0.816–0.912) and 0.792 (CI95, 0.721–0.861), respectively. When we applied a cutoff of 0, specificities/negative predictive values in eradicable and non-eradicable source of infection groups were 84.7%/95.6% and 95.5%/95.0%, respectively (Table 2). Conclusion Our prediction scores based on adequate source control and use of effective antibiotics showed high specificities and negative predictive values. Therefore, we could expect these score systems to contribute to reducing unnecessary FUBC in GNB. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Early administration of susceptible antibiotics is crucial in Gram-negative bacteremia (GNB), especially in immunocompromised patients. We aimed to explore risk factors and clinical outcomes of carbapenem non-susceptible (Carba-NS) GNB in patients with acute myelogenous leukemia (AML). Methods Cases of all GNB during induction or consolidation chemotherapy for AML in a 15-year period in a tertiary hospital were retrospectively reviewed. Independent risk factors for Carba-NS GNB were sought and its clinical outcomes were compared with those of carbapenem susceptible (Carba-S) GNB. Results Among 485 GNB cases from 930 patients, 440 (91%) were Carba-S and 45 (9%) were Carba-NS GNB. Frequent Carba-NS isolates were Stenotrophomonas maltophilia (n = 23), Pseudomonas aeruginosa (n = 11), and Acinetobacter baumannii (n = 10). Independent risk factors for Carba-NS GNB were carbapenem use at the onset of GNB (aOR [95% CI], 78.6 [24.4–252.8]; P < 0.001), the isolation of imipenem-resistant A. baumannii in the prior 1 year (aOR [95% CI], 14.6 [2.7–79.9]; P = 0.002), time interval from chemotherapy to GNB ≥20 days (aOR [95% CI], 4.7 [1.7–13.1]; P = 0.003), and length of hospital stay ≥30 days (aOR [95% CI], 3.4 [1.3–9.1]; P = 0.013). Except breakthrough GNBs which occurred during carbapenem treatment, the frequency of Carba-NS GNB was 48% (19/40) in cases having ≥2 risk factors other than carbapenem use. 30-day overall mortality (Carba-NS, 36% vs. Carba-S, 6%; P < 0.001) and in-hospital mortality (Carba-NS, 47% vs. Carba-S, 9%; P < 0.001) were significantly higher in Carba-NS GNB. Conclusion Carba-NS GNB in AML patients was independently associated with the use of carbapenem, the past isolation of resistant organism, and late onset of GNB, and its clinical outcomes were poorer than those of Carba-S GNB. Carba-NS organisms should be considered for antibiotic selection in AML patients having these risk factors. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]