Ming Chi Li

Pneumocystis jiroveci pneumonia in immunocompromised patients: Delayed diagnosis and poor outcomes in non-HIV-infected individuals

BACKGROUNDnPneumocystis jiroveci pneumonia (PJP) is a life-threatening disease in immunocompromised patients. Improved knowledge about the varied characteristics and management in different populations may guide treatment.nnnMETHODSnWe evaluated the clinical characteristics, management, and outcomes of patients with PJP diagnosed by nested polymerase chain reaction at a medical center in southern Taiwan from 2008 to 2011. The risk factors of mortality among non-human immunodeficiency virus (HIV)-infected patients were analyzed.nnnRESULTSnDuring the study period, there were 43 cases of PJP, and the common underlying diseases were HIV infection (23 patients, median CD4 count: 19/μl) and malignancy. The HIV-infected patients had a younger age (36.9 ± 13.7 vs. 50.2 ± 16.2 years, p = 0.006), a lower body mass index (19.9 ± 2.3 vs. 22.0 ± 3.7 kg/m(2), p = 0.035), a longer duration of symptoms before admission (24 ± 29 vs. 7 ± 15 days, p = 0.035), and a lower pneumonia severity index (56 ± 25 vs. 99 ± 35, p < 0.001) than non-HIV-infected patients. A delay between admission and starting antimicrobial therapy for PJP (10 ± 10 days vs. 1 ± 3 days, p = 0.004) and a high crude mortality (12/20, 60% vs. 2/23, 9%, p = 0.001) were noted in non-HIV-infected patients. In the univariate analysis, the risk factors for mortality were a low lymphocyte count (p < 0.05) and shock during hospitalization (p = 0.004).nnnCONCLUSIONnA delay in the initiation of antimicrobial therapy for PJP and severe pneumonia were more common in the non-HIV-infected patients and were most likely related to the poor prognosis. The utilization of sensitive diagnostic tools to facilitate early diagnosis and treatment may improve the clinical outcomes of non-HIV-infected patients with PJP.

Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates

ABSTRACT A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 μg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.

Clinical impact of Gram-negative nonfermenters on adults with community-onset bacteremia in the emergency department

BACKGROUNDnTo determine clinical predictors and impact of Gram-negative nonfermenters (GNNFs) infections among adults with community-onset bacteremia in the emergency department (ED).nnnMETHODSnAdults with bacteremia visiting the ED from January 2007 to June 2008 were identified retrospectively. Demographic characteristics, underlying illnesses, clinical conditions, bacteremic pathogens, antimicrobial agents, and outcome, were retrieved from chart records.nnnRESULTSnAfter the exclusion of 261 patients with contamination of blood cultures and 24 patients referred from other hospitals, 518 adults with community-onset bacteremia were eligible; their mean age was 65.1 years, with slight predominance of female (262 patients, 50.6%). Of a total of 565 bacteremic isolates, Escherichia coli (228 isolates, 40.4%) and Klebsiella pneumoniae (100, 17.7%) were the major microorganisms. GNNFs caused bacteremia in 31 (6.0%) patients. A higher proportion of inappropriate antibiotic therapy in the ED (87.1% vs. 26.5%, p < 0.001) and higher 28-day crude mortality rate (19.4% vs. 8.4%, p = 0.05) were observed in bacteremic patients caused by GNNFs than those not caused by GNNFs. In further analysis of Kaplan-Meier survival curve, patients with GNNF bacteremia had a worse outcome than those due to other pathogens (p = 0.04). Multivariate analysis revealed that the independent predictors related to GNNF bacteremia included surgery during previous 4 weeks prior to ED arrival [odds ratio (OR), 10.79; 95% confidence interval (CI), 1.84-63.24; p = 0.01], residents in long-term healthcare facilities (OR, 4.62; 95% CI, 2.08-10.29; p < 0.001), and malignancy (OR, 2.24; 95% CI, 1.10-5.40; p = 0.02).nnnCONCLUSIONnFor adults with bacteremia visiting the ED, GNNF is associated with a higher mortality rate and more inappropriate empirical antibiotic therapy in the ED. To allow early administration of empirical antibiotics, several clinical predictors of GNNF infections were identified.

Virulence diversity among bacteremic aeromonas isolates: Ex vivo, animal, and clinical evidences

Background The objective of this study was to compare virulence among different Aeromonas species causing bloodstream infections. Methodology/Principal Findings Nine of four species of Aeromonas blood isolates, including A. dhakensis, A. hydrophila, A. veronii and A. caviae were randomly selected for analysis. The species was identified by the DNA sequence matching of rpoD. Clinically, the patients with A. dhakensis bacteremia had a higher sepsis-related mortality rate than those with other species (37.5% vs. 0%, Pu200a=u200a0.028). Virulence of different Aeromonas species were tested in C. elegans, mouse fibroblast C2C12 cell line and BALB/c mice models. C. elegans fed with A. dhakensis and A. caviae had the lowest and highest survival rates compared with other species, respectively (all P values <0.0001). A. dhakensis isolates also exhibited more cytotoxicity in C2C12 cell line (all P values <0.0001). Fourteen-day survival rate of mice intramuscularly inoculated with A. dhakensis was lower than that of other species (all P values <0.0001). Hemolytic activity and several virulence factor genes were rarely detected in the A. caviae isolates. Conclusions/Significance Clinical data, ex vivo experiments, and animal studies suggest there is virulence variation among clinically important Aeromonas species.

Aeromonas stool isolates from individuals with or without diarrhea in southern Taiwan: Predominance of Aeromonas veronii

BACKGROUNDnAlthough aeromonads are important pathogens causing invasive infections in southern Taiwan, Aeromonas-associated intestinal infections have been rarely mentioned.nnnPURPOSEnThe aim of this study was to understand the frequency of isolation and clinical significance of aeromonads recovered from adult stool samples in southern Taiwan.nnnMETHODSnDuring a 15-month study period, 514 adults with diarrhea and 167 asymptomatic controls were prospectively screened for the presence of aeromonads in stools. The identity of Aeromonas species was determined by the rpoD sequencing. Clinical information was retrieved from medical records, and inxa0vitro cytotoxicity assay and polymerase chain reaction detection of putative virulent genes were performed.nnnRESULTSnThirteen (2.5 %) of 514 diarrheal patients and six (3.6%) of 167 asymptomatic controls had Aeromonas isolates in their stools. Of 11 diarrheal patients with available clinical information, Aeromonas veronii, the predominant species, was noted in six patients, and another potential enteropathogen was present in four patients. The cytotoxicity of A. veronii isolates to the HT-29 cell line was more potent in the isolates from diarrheal patients than those from asymptomatic controls (pxa0=xa00.015). The cytotoxicity of A. veronii isolates was more potent than that of A. caviae from symptomatic patients (pxa0=xa00.001). Putative virulence markers, including AHCYTONE, ascV, ascF-ascG, and aexT, were detected exclusively in A. veronii. The presence of the ascV gene was associated with cytotoxicity in A. veronii isolates. All Aeromonas isolates were susceptible to varied antimicrobial agents, except ampicillin/sulbactam.nnnCONCLUSIONnA. veronii is the predominant species in stools from individuals with or without diarrhea in southern Taiwan.

Time-to-positivity of blood culture: An independent prognostic factor of monomicrobial Pseudomonas aeruginosa bacteremia.

BACKGROUND/PURPOSEnPseudomonas aeruginosa bacteremia is an important cause of nosocomial infections with high morbidity and mortality. Time-to-positivity (TTP) of blood cultures is considered to be a predictor of the clinical outcome for bacteremia. The aim of the study is to investigate the relationship between TTP and clinical outcomes in patients with monomicrobial P. aeruginosa bacteremia.nnnMETHODSnFrom January 2013 to June 2014, a retrospective cohort study was conducted in a 1200-bed tertiary care hospital. The cases of monomicrobial P. aeruginosa bacteremia were studied. TTP and clinical parameters were determined and analyzed.nnnRESULTSnIn 139 cases of P. aeruginosa bacteremia, TTP ≤ 13 hours was associated with higher Pitt bacteremia scores (5.3xa0±xa04.2 vs. 2.3xa0±xa02.8, pxa0<xa00.001), severe sepsis (66.1% vs. 35.0%, pxa0<xa00.001), higher 30-day mortality rate (54.2% vs. 15.0%, pxa0<xa00.001), longer hospitalization in the survivors (25.6xa0±xa048.5 days vs. 16.3xa0±xa015.3 days, pxa0=xa00.16), and more admission to intensive care unit (27.2% vs. 16.3%, pxa0=xa00.14). Risk factors for 30-day mortality in the univariate analysis included corticosteroid exposure, primary bacteremia, concurrent pneumonia, a high Pitt bacteremia score, severe sepsis, and TTP ≤ 13 hours. In the multivariate analysis, primary bacteremia, a pulmonary origin of bacteremia, severe sepsis, and TTP ≤ 13 hours were independent risk factors for 30-day mortality.nnnCONCLUSIONnIn cases of monomicrobial P. aeruginosa bacteremia, a short TTP (≤ 13 hours) provides prognostic information, in addition to clinical parameters.

Salmonella infective endocarditis

OBJECTIVEnSalmonella endocarditis is so rarely reported that its clinical features, prognosis, and optimal treatment remain unclear. In this paper, we report a female with nontyphoid Salmonella endocarditis complicated with perivalvular abscess. We also review and summarize other cases reported in the English literature.nnnMETHODSnUsing the key words Salmonella, infective endocarditis, and mural endocarditis to search the PubMed database, we reviewed case reports on Salmonella endocarditis published between 1976 and 2014 and case series of infective endocarditis that included at least 500 cases.nnnRESULTSnSalmonella species were rare infective endocarditis pathogens. Among 16 large case series, they accounted for less than 0.01% and up to 2.9% of bacterial endocarditis cases. From 1976 to 2014, a total of 87 cases of typhoid and nontyphoid Salmonella endocarditis were reported, which included 42 cases in 1976-1984, 30 cases in 1986-2002, and 15 cases in 2003-2014. Men predominated among the cases (58.6%), and the mean age was approximately 50-60 years. The major affected valves were the mitral valves (33.3%). Mural endocarditis was common (26.4%). Perivalvular abscess was only reported in 10.5% (6 cases) of 57 cases. The overall mortality rate was 42.5% and decreased over time from 69.0% to 13.3% during the three study periods.nnnCONCLUSIONnSalmonella endocarditis, although rare, may cause purulent infections in the perivalvular area or myocardium and lead to substantial mortality.

Fluoroquinolone therapy for bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae

BACKGROUND/PURPOSEnFor extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, carbapenems are recommended as first line therapy, and clinical data on the therapeutic efficacy of fluoroquinolones (FQs) is limited. This study compares the efficacy of FQs and carbapenems for bloodstream infections caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.nnnMETHODSnBetween 2008 and 2010, adults with ESBL-producing E. coli or K. pneumoniae bacteremia at two medical centers were reviewed. Adults receiving definitive FQ or carbapenem therapy were compared in a propensity score-matched analysis, and 30-day mortality was the primary endpoint.nnnRESULTSnA total of 299 patients were eligible. Patients receiving a FQ (nxa0=xa024), either ciprofloxacin or levofloxacin, had a lower 30-day mortality rate than those with carbapenem therapy (8.3%, 2/24 vs. 23.3%, 64/275; pxa0=xa00.12). Multivariate regression analysis revealed that a critical illness [Pitt bacteremia scorexa0≥xa04 points; odds ratio (OR), 7.09; pxa0<xa00.001], rapidly fatal underlying disease (OR, 5.73; pxa0<xa00.001), and hospital-associated infection (OR, 2.57; pxa0=xa00.01) were independently associated with 30-day mortality. By contrast, FQ definitive therapy was a protective factor compared with carbapenems (OR, 0.18; pxa0=xa00.04). There were 72 matched cases with carbapenem therapy in a propensity score-matched analysis, and a difference in the 30-day mortality rate of two groups was noted (8.3% vs. 29.2%; pxa0=xa00.05).nnnCONSLUSIONnFor ESBL-producing E. coli or K. pneumoniae bacteremia, ciprofloxacin or levofloxacin, if active inxa0vitro, can be considered as a carbapenem-sparing alternative.

Community-onset Clostridium difficile infection at a tertiary medical center in southern Taiwan, 2007–2015

BACKGROUNDnClostridium difficile infection (CDI) is well-known as the major cause of infectious diarrhea in hospitalized patients. Community-onset CDI (CO-CDI) is an emerging threat. However, clinical information of CO-CDI in Taiwan remains scarce.nnnMETHODSnA retrospective study was conducted at a medical center in southern Taiwan. Symptomatic patients between 2007 and 2015 with C. difficile toxin or tcdB detected in stool were identified as CDI, and were classified as CO-CDI [including community-associated CDI (CA-CDI) and community-onset health care facility-associated CDI (CO-HCFA-CDI)] and health care facility-onset CDI (HCFO-CDI).nnnRESULTSnOf 427 patients, 15 (3.5%) were CA-CDI, 49 (11.5%) CO-HCFA-CDI, and 363 (85.0%) HCFO-CDI. Despite major involvement of the elderly (mean age: 66.1xa0years vs. 69.9xa0years, pxa0=xa00.46), no significant differences were noted between CA-CDI and CO-HCFA-CDI groups, except that solid organ cancer was more common in the CO-HCFA-CDI group. The CO-CDI group more often presented with abdominal pain but had shorter hospital stays and less exposure of proton-pump inhibitors or broad-spectrum antibiotics than the HCFO-CDI group did. The mortality rate related to CDI was 4.7% (3 patients) in the CO-CDI group. Despite a lower in-hospital mortality rate in the CO-CDI group (10.9% vs. 22.0%; pxa0=xa00.04), the recurrence rate was similar (10.9% vs. 7.2%; pxa0=xa00.3).nnnCONCLUSIONSnCO-CDI is not common but associated with substantial morbidity and mortality. Physicians should put CDI into consideration among patients who present community-onset fever, diarrhea, or abdominal pain alone or in combination.

Legionnaires’ disease at a medical center in southern Taiwan

BACKGROUND/PURPOSEnLegionella pneumophila had been recognized as a pathogen for both healthcare-associated and community-acquired pneumonia. We aimed to evaluate clinical features and outcomes of patients with Legionnaires disease at a tertiary medical center in southern Taiwan.nnnMETHODSnFrom January 2005 to December 2013, a retrospective study of adult cases of Legionnaires disease was conducted in a 1200-bed tertiary hospital. Their medical records were reviewed for further evaluation and analysis.nnnRESULTSnA total of 61 cases of Legionnaires disease were identified during the study period. Their mean age was 61.1 years, with male predominance (43, 70.5%). Among them, 30 (49.2%) had healthcare-associated pneumonia (HCAP), 20 (32.8%) had community-acquired pneumonia, and notably 11 (18.0%) were caregivers. Patients with healthcare-associated pneumonia tend to have higher Charlson comorbidity scores than those with community-acquired pneumonia (3.6±2.4 vs. 1.9±1.9, p=0.008) and caregivers (0.5±0.5, p<0.001). Six patients died, resulting in an in-hospital mortality rate of 9.8%. Underlying cancer (66.7% vs. 20.0%, p=0.028) and a higher Charlson comorbidity score (4.7±2.6 vs. 2.2±2.2, p=0.013) were related to a fatal outcome.nnnCONCLUSIONnL. pneumophila remains an important pathogen for pneumonia acquired from the community or associated with healthcare facility. Healthy caregivers may potentially be at risk for Legionella infection in certain clinical settings.