Ching Chi Lee

Cefepime Therapy for Monomicrobial Bacteremia Caused by Cefepime-Susceptible Extended-Spectrum Beta-Lactamase–Producing Enterobacteriaceae: MIC Matters

BACKGROUND Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae isolates are important clinical pathogens. In addition, the efficacy of cefepime for such infections is controversial. METHODS We performed a retrospective study of monomicrobial bacteremia caused by ESBL producers at 2 medical centers between May 2002 and August 2007. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) in a propensity score-matched analysis to assess therapeutic effectiveness. The 30-day crude mortality is the primary endpoint. RESULTS A total of 178 patients were eligible for the study. Patients who received cefepime (n = 17) as definitive therapy were more likely to have a clinical failure (odds ratio [OR] 6.2; 95% confidence interval [CI], 1.7-22.5; P = .002), microbiological failure (OR 5.5; 95% CI, 1.3-25.6; P = .04), and 30-day mortality (OR 7.1; 95% CI, 2.5-20.3; P < .001) than those who received carbapenem therapy (n = 161). Multivariate regression revealed that a critical illness with a Pitt bacteremia score ≥ 4 points (OR 5.4; 95% CI, 1.4-20.9; P = .016), a rapidly fatal underlying disease (OR 4.4; 95% CI, 1.5-12.6; P = .006), and definitive cefepime therapy (OR 9.9; 95% CI, 2.8-31.9; P < .001) were independently associated with 30-day crude mortality. There were 17 case-control pairs in the propensity scores matched analysis. The survival analysis consistently found that individuals who received cefepime therapy had a lower survival rate (log-rank test, P = .016). CONCLUSIONS Based on the current Clinical and Laboratory Standards Institute susceptible breakpoint of cefepime (minimum inhibitory concentration ≤ 8 μg/mL), cefepime definitive therapy is inferior to carbapenem therapy in treating patients with so-called cefepime-susceptible ESBL-producer bacteremia.

Necrotizing fasciitis in patients with liver cirrhosis: predominance of monomicrobial Gram-negative bacillary infections

Necrotizing fasciitis (NF), a rare but severe infection, usually occurs in individuals with underlying chronic illness, but its clinical presentation among cirrhotic patients is infrequently discussed. Forty-two cirrhotic patients with 47 episodes of NF between 1995 and 2006 were analyzed. Their mean age was 55.6 years, with male preponderance (34 patients, 81%). Lower extremities were mainly involved (70%). Of 42 episodes with identified pathogens, 41 (97%) were monomicrobial infections and were caused mainly by Gram-negative rods (GNBs) (32, 76%), including Vibrio (15, 36%), Klebsiella (9, 21%), and Aeromonas spp. (6, 14%). As compared with NF caused by Gram-positive cocci (GPCs), NF caused by GNBs tended to have concurrent bacteremia (81% versus 50%, P=0.09) and initially presented with septic shock (75% versus 30%, P=0.02). However, the in-hospital mortality rate was similar for NF caused by GNBs and GPCs (34% versus 30%, P=1.00). In multivariate analyses, higher sepsis-related organ failure assessment scores (>8) and Child-Pugh class C at initial presentation were independently associated with poor prognoses.

Clostridium difficile Infection at a Medical Center in Southern Taiwan: Incidence, Clinical Features and Prognosis

BACKGROUND/PURPOSE An increase in incidence of Clostridium difficile infection (CDI) among Western countries has been noted in recent years. Epidemiological data of CDI are scarce in Taiwan. This study is intended to depict the clinical features of CDI at a medical center in Southern Taiwan. METHODS From January 1, 2007 to March 31, 2008, hospitalized patients with CDI (defined as the presence of gastrointestinal symptoms and fecal C. difficile toxin) were identified. Their medical records were reviewed for further evaluation. RESULTS A total of 86 cases of CDI were identified in the study period. The incidence was 42.6 cases per 100,000 patient-days, or 3.4 cases per 1,000 discharges, and was highest in intensive care units (110.6 cases per 100,000 patient-days). Variable incidence rates were noted in different wards, and prevalence was higher in the infectious ward. Diarrhea, fever, and abdominal distension were common in 82 (95.3%), 47 (54.7%), and 29 (33.7%) patients, respectively. Metronidazole was the initial therapeutic regimen for 83 (96.5%) patients. Prolonged diarrhea was noted in 31 (36.4%) patients, especially in those on hemodialysis therapy. Recurrence was noted in 7 (8.1%) patients. Fecal carriage of vancomycin-resistant Enterococcus colonization was found in three patients after therapy for CDI. All-cause mortality rate of patients with CDI at 30 days was 23.3%. CONCLUSION CDI is increasingly being recognized within the medical departments, and should be considered in hospitalized adults with diarrhea, fever, or abdominal distension alone, or in combination.

Clinical manifestations, antimicrobial therapy, and prognostic factors of monomicrobial Acinetobacter baumannii complex bacteremia

OBJECTIVES Bacteremia due to Acinetobacter baumannii complex (ABC), which composed of four genomic species (gen. sp.), is a serious and potentially fatal condition. The epidemiology and outcome of such infections due to individual gen. sp. remain undefined. METHODS A retrospective study of patients with monomicrobial ABC bacteremia over six years was conducted at a medical center to determine the association of gen. sp. with clinical outcome. RESULTS Included were 291 patients with monomicrobial ABC bacteremia. Of them, 222 (76.3%) patients had bacteremia caused by gen. sp. 2, i.e. A. baumannii. The presence of multidrug-resistant phenotype was the only independent predictor of Acinetobacter gen. sp. 2 bacteremia (adjusted odd ratio, 7.5; 95% confidence interval, 3.8-14.7; P < 0.001). Patients with Acinetobacter gen. sp. 2 bacteremia had a higher sepsis-related (P = 0.006) and 30 day (P = 0.028) mortality rates than the non-Acinetobacter gen. sp. 2 group. The fatal outcome was independently associated with high SPAS II scores (P = 0.002), rapidly fatal underlying diseases (P = 0.002), bacteremia caused by Acinetobacter gen. sp. 2 (P = 0.01), inappropriate definitive antimicrobial therapy (P < 0.001), and severe sepsis (P < 0.001). CONCLUSION Acinetobacter gen. sp. 2 bacteremia heralded a worse clinical outcome, and therefore the gen. sp. identification of ABC bacteremic isolates is justified.

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

BACKGROUND Pneumocystis 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. METHODS We 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. RESULTS During 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). CONCLUSION A 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.

The impact of overcrowding on the bacterial contamination of blood cultures in the ED.

OBJECTIVES This study aims to determine the risk factors associated with the bacterial contamination of blood cultures among adults visiting the emergency department (ED). METHODS Clinical variables and medical records of adults with bacterial growth of blood cultures in the ED as well as the degree of ED crowding, between August 2007 and July 2008, were prospectively collected. RESULTS Of the 11 491 adults who underwent blood culture sampling, the medical records of 558 (4.86%) eligible patients with bacterial growth in their blood cultures were analyzed. Most patients (366, or 3.19%) had true bacteremia, whereas 192 (1.67%) were regarded as contaminated. In multivariate analyses, ED overcrowding (scoring was based on a National Emergency Department Overcrowding Study [NEDOCS] score ≥ 100 points) was independently associated with blood culture contamination (odds ratio [OR], 1.58; P = .04). In contrast, other medical comorbidities, such as liver cirrhosis (OR, 0.31; P = .02), thrombocytopenia (<100 000/mm(3); OR, 0.28; P = .002), or high serum levels of C-reactive protein (>100 mg/L; OR, 0.24; P < .001), were negatively associated with blood culture contamination. On further analysis of the 5 crowding categories as stratified by NEDOCS scores, which included not busy and busy (0-60 points), extremely busy but not overcrowded (60-100), overcrowded (100-140), severely overcrowded (140-180), and dangerously overcrowded (180-200), there was a strong correlation between blood culture contamination rates and the degrees of ED crowding (γ = 0.99, P < .001). CONCLUSIONS Emergency department overcrowding may have an adverse impact on the quality of clinical care, including increasing the risk of blood culture contamination.

Carbapenem Therapy for Bacteremia due to Extended-spectrum β-lactamase-producing Escherichia coli or Klebsiella pneumoniae: Implications of Ertapenem Susceptibility

ABSTRACT A retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs ≤ 0.25 μg/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P = 0.1) or sepsis-related mortality rate (P = 0.2) for patients with bacteremia caused by ESBL-producing K. pneumoniae (140 isolates, 55.8%) and E. coli (111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34; P < 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24; P = 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88; P = 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P = 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ≤ 0.25 μg/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 μg/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of ≤0.5 μg/ml was similar to the mortality for those whose isolates had MICs of >0.5 μg/ml (P = 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems for Enterobacteriaceae.

Pitfalls in using serum C-reactive protein to predict bacteremia in febrile adults in the ED

OBJECTIVES The diagnostic performance of serum C-reactive protein (CRP) in prediction of bacteremia among febrile patients visiting an emergency department (ED) was analyzed. METHODS During randomly selected 96 days between August 2006 and July 2007, a prospective study of febrile adults visiting the ED of a medical center was conducted to analyze the clinical characters associated with bacteremia. RESULTS Of the total 454 febrile adults enrolled, their mean age was 54.1 years, and 232 (54.6%) were women. Major comorbidities included cardiovascular disease (137 patients, or 30.1%) and diabetes mellitus (105, or 23.1%). Seventy-four patients (16.2%) had true bloodstream infections with the predominance of monomicrobial gram-negative bacteremia in 49 patients (10.7%). Four risk factors, including low platelet count (<100 000/mm(3); odds ratio [OR], 4.19; 95% confidence interval [CI], 1.85-9.47; P = .001), high blood urea nitrogen (>20 mg/dL; OR, 4.61; 95% CI, 2.56-8.31; P < .001), high fever (>39.0°C; OR, 3.67; 95% CI, 2.05-6.59; P < .001), and high Pittsburg bacteremia scores (≧4 points; OR, 2.95; 95% CI, 1.01-8.57; P = .04) were independently associated with bacteremic episodes. Of note, high CRP (>150 mg/dL; OR, 1.75; 95% CI, 0.73-3.99; P = .21) was not an independent risk factor. In further analysis, the difference of serum CRP levels between bacteremic and nonbacteremic adults was significant only when the period from fever onset to ED arrival was more than 12 hours. CONCLUSIONS The CRP level was not reliable to distinguish the bacteremia from nonbacteremic infection, whereas duration after fever onset was less than 12 hours. Clinicians must consider the history of fever onset to improve the accuracy of early prediction of serum CRP before the microbiological results of blood cultures is available.

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.

Atypical presentations of dengue disease in the elderly visiting the ED

OBJECTIVE The objective was to compare the clinical characteristics of elderly and young adult patients with dengue in the emergency department (ED). METHODS Demographic characteristics, clinical presentation, disease severity, laboratory characteristics, and outcomes were analyzed prospectively as a case-control study. RESULTS Of the 193 adults with serologically confirmed dengue disease in 2007, 31 (16.1%) were elderly patients (aged ≥65) and 162 were young adults (aged <65). More dengue hemorrhagic fever (12.9% vs 2.5%, P = .02), a longer ED stay (13.3 vs 8.6 hours, P = .004), a longer hospital stay (7.4 vs 3.4 days, P < .001), a higher Simplified Acute Physiology Score II in the ED (29.7 vs 17.4, P < .001), and a higher rate of at least 1 comorbidity (61.8 vs 22.8%, P < .001) were found in the elderly. However, the length of the intensive care unit stay (elderly 0.7 vs young adults 0.3 day, P = .47) and the 14-day mortality rate (0% vs 0.6%, P = 1.00) were similar. Of note, in terms of clinical presentations of dengue in the ED, there were more elderly patients with isolated fever (41.9% vs 17.9%, P = .003) and fewer with typical presentation (41.9% vs 75.9%, P = <.001) than there were young adults. CONCLUSIONS The present study found a higher number of atypical presentations, a longer hospitalization, and a higher degree of clinical illness in elderly patients with dengue.