Clinical impact of cefepime breakpoint in patients with carbapenem-resistant Klebsiella pneumoniae bacteraemia.

The application of cefepime breakpoint for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia has not been explored. Adult cases of monomicrobial bloodstream infection (BSI) caused by cefepime-susceptible [minimum inhibitory concentration (MIC) ≤8 mg/L] K. pneumoniae isolates with carbapenem resistance between 2010 and 2015 were reviewed. Patients treated with cefepime were compared with those treated by other active agents using a propensity score-matched analysis to assess therapeutic effectiveness. The primary endpoint was 30-day crude mortality. A total of 114 patients experienced cefepime-susceptible CRKP bacteraemia and 40 (35.1%) died during hospitalisation. A total of 33 patients (28.9%) received cefepime therapy. Fifteen patients (13.2%) had BSI due to carbapenemase-producing isolates, and 86.7% (13/15) of carbapenemase-producing isolates were classified as cefepime susceptible dose-dependent (SDD). In the multivariate logistic regression analysis, 30-day mortality was independently associated with the presence of a critical illness [adjusted odds ratio (aOR) = 12.89, 95% confidence interval (CI) 3.88-42.83; P < 0.001], pneumonia (aOR = 5.97, 95% CI 1.65-21.76; P = 0.007) and rapidly fatal underlying disease (aOR = 6.43, 95% CI 1.30-31.09; P = 0.02). In contrast, cefepime-based therapy (aOR = 0.03, 95% CI 0.003-0.38; P = 0.006) and combination therapy (aOR = 0.09, 95% CI 0.02-0.36; P = 0.001) were protective against a fatal outcome. Based on current breakpoints for Enterobacterales, cefepime therapy was not associated with an unfavourable outcome for CRKP BSI with MIC-based dosing strategies. However, the susceptibility result of SDD to cefepime should alert clinicians for possible therapeutic failure.

Treatment Outcome of Bacteremia Due to Non-Carbapenemase-producing Carbapenem-Resistant Klebsiella pneumoniae Bacteremia: Role of Carbapenem Combination Therapy.

PURPOSE: Infections caused by carbapenemase-producing Klebsiella pneumoniae are emerging causes of morbidity and mortality worldwide. Optimal treatment for non-carbapenemase-producing carbapenem-resistant K pneumoniae (nCP-CRKP) bacteremia remains undefined. The goal of this study was to assess the clinical outcome, predictors of mortality, and therapeutic strategy of carbapenems for nCP-CRKP bacteremia. METHODS: A retrospective study of monomicrobial bacteremia caused by nCP-CRKP, at a medical center between 2010 and 2015 was conducted. CRKP which was defined as a minimum inhibitory concentration (MIC) of ≥ 2 for ertapenem or ≥ 4 mg/L for meropenem, or imipenem. Multiplex polymerase chain was applied to detect carbapenemase genes. The patients definitively treated with combination therapy were compared with monotherapy using a propensity score-matched analysis to assess therapeutic effectiveness. The primary end point was the 30-day crude mortality and clinical prognostic factors were assessed. FINDINGS: Overall 171 patients met criteria were eligible for the study and their overall 30-day mortality rate was 38.6%. The multivariate logistic regression analysis showed that combination therapy was associated with a lower 30-day mortality rate (adjusted odds ratio [aOR], 0.11; 95% CI, 0.03-0.43; P = 0.001) and less clinical (aOR, 0.21; 95% CI, 0.08-0.58; P = 0.003) and microbiologic (aOR, 0.36; 95% CI, 0.19-0.71; P = 0.003) failure. However, the 30-day mortality rate in the cases infected by a pathogen with a meropenem MIC ≤8 mg/L receiving carbapenem-containing or carbapenem-sparing combination regimens was similar (15 of 58 [25.9%] vs 5 of 20 [23.3%]; P = 1.0). IMPLICATIONS: Combination therapy, regardless of carbapenem-containing or carbapenem-sparing, with one or more active agents improved survival more than monotherapy and was more effective in patients with critical illness. (Clin Ther. 2020; 42:XXX-XXX) © 2020 Elsevier HS Journals, Inc.

Bloodstream infections in hospitalized adults with dengue fever: Clinical characteristics and recommended empirical therapy.

BACKGROUND: Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed. METHODS: Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected. RESULTS: Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week. CONCLUSIONS: BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.

Antimicrobial susceptibility of clinical Enterobacteriaceae isolates at the emergency department in a regional hospital: A threat of extended spectrum beta-lactamase-producers among nursing home residents.

BACKGROUND/PURPOSE: The prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in nursing home residents has rarely been reported in Taiwan. METHODS: A retrospective study was performed at medical wards of a district hospital at southern Taiwan between July 2009 and June 2011. Patients were included if they were older than 18 years, admitted via the emergency department, and their blood, sputum, or urine culture revealed the growth of Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. From each patient only the first isolate from the infection site was included. Antimicrobial susceptibility was determined using the disc diffusion method. RESULTS: Overall, 827 patients were included, with 354 (42.8%) coming from the community and 473 (57.2%) referred from a nursing home. Of the isolates acquired in nursing home, 45.5% (215/473) harbored ESBL. By contrast, 20.6% (73) of 354 isolates acquired in the community exhibited the ESBL production phenotype (p < 0.001). Of the isolates obtained from blood, urine, or sputum, 28.2% (37/131), 36.0% (208/578), or 36.4% (43/118) harbored ESBL, respectively, whereas 41% (211) of 515 E. coli isolates, 34.3% (72) of 210 K. pneumoniae, and 4.9% (5) of 102 P. mirabilis had ESBL. In general, the isolates from a nursing home or those with ESBL had lower antimicrobial susceptibility rates than those from the community or those without ESBL production. Only amikacin, piperacillin/tazobactam, ertapenem, and imipenem/meropenem were active against >90% Enterobacteriaceae isolates, irrespective of ESBL production. CONCLUSION: ESBL production was common among clinical Enterobacteriaceae isolates, especially E. coli or those isolated from nursing home residents.

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

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.