Search

In this study, the therapeutic efficacy of third-generation cephalosporins (3GCs) was compared with that of broader-spectrum β-lactams (BSBLs) [fourth-generation cephalosporins (4GCs) and carbapenems] as empirical therapy in adults with community-onset monomicrobial Enterobacteriaceae bacteraemia. Compared with those in the 3GC group (n = 477), a significantly higher proportion of patients in the BSBL group (n = 141) had initial presentation with severe sepsis or septic shock, critical illness (Pitt bacteraemia score ≥4) at bacteraemia onset and fatal co-morbidities (McCabe classification). For propensity score matching, 318 of the 477 patients in the 3GC group were matched with 106 patients in the BSBL group with the closest propensity scores on the basis of five independent predictors of 28-day mortality. After appropriate matching, no significant differences were observed in major baseline characteristics between the 3GC and BSBL groups in terms of causative micro-organism, bacteraemia severity, major source of bacteraemia, major co-morbidities and severity of co-morbidity. Consequently, the early clinical failure rate (12.9% vs. 12.3%; P = 0.87), bacteraemia severity (Pitt bacteraemia score ≥4; 4.6% vs. 8.2%; P = 0.17) at Day 3, and 3-day (3.8% vs. 7.5%; P = 0.11) and 28-day (13.2% vs. 17.0%; P = 0.33) crude mortality rates between the two groups were similar. These data suggest that the efficacy of 3GCs is similar to that of 4GCs or carbapenems when used as empirical antimicrobial therapy for community-onset Enterobacteriaceae bacteraemia., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Both fluoroquinolones (FQs) and third-generation cephalosporins (3rd-GCs) are commonly prescribed to treat bloodstream infections, but comparative efficacies between them were rarely studied. Demographics and clinical characteristics of 733 adults with polymicrobial or monomicrobial community-onset bacteremia empirically treated by an appropriate FQ (n = 87) or 3rd-GC (n = 646) were compared. A critical illness (respectively, 8.0% versus 19.0%; P = 0.01), an initial syndrome with severe sepsis (33.3% versus 50.3%; P = 0.003), or a fatal outcome at 28 days (4.6% versus 10.5%; P = 0.08) was less common in the FQ group. A total of 645 (88.0%) patients were febrile at initial presentation, and the FQ group with (FQ group versus 3rd-GC group, respectively, 7.6 days versus 12.0 days; P = 0.04) and without (3.8 days versus 5.4 days; P = 0.001) a critical illness had a shorter time to defervescence than the 3rd-GC group. By the propensity scores, 87 patients with appropriate FQ therapy were matched with 435 treated by 3rd-GC therapy at a ratio of 1:5, and there were no significant differences in terms of bacteremia severity, comorbidity severity, major comorbidities, causative microorganisms, and bacteremia sources between groups. Moreover, crude mortality rates at 28 days (FQ group versus 3rd-GC group, respectively, 4.6% versus 7.8%; P = 0.29) did not differ significantly. However, the time to defervescence was shorter in the FQ group (4.2 ± 3.6 versus 6.2 ± 7.6 days; P < 0.001). Conclusively in the adults with community-onset bacteremia, appropriate empirical FQ therapy was related to shorter time to defervescence than with 3rd-GC therapy, at least for those without a critical illness., (Copyright © 2017 American Society for Microbiology.)

In this study, the therapeutic efficacy of cefazolin was compared with that of extended-spectrum cephalosporins (ESCs) (cefotaxime, ceftriaxone and ceftazidime) as appropriate empirical therapy in adults with community-onset monomicrobial bacteraemia caused by Escherichia coli, Klebsiella spp. or Proteus mirabilis (EKP). Compared with cefazolin-treated patients (n = 135), significantly higher proportions of patients in the ESC treatment group (n = 456) had critical illness at bacteraemia onset (Pitt bacteraemia score ≥4) and fatal co-morbidities (McCabe classification). Of the 591 patients, 121 from each group were matched using propensity score matching (PSM) based on the following independent predictors of 28-day mortality: fatal co-morbidities (McCabe classification); Pitt bacteraemia score ≥4 at bacteraemia onset; initial syndrome of septic shock; and bacteraemia due to pneumonia. After appropriate PSM, no significant differences were observed in the early clinical failure rate (10.7% vs. 7.4%; P = 0.37), the proportion of critical illness (Pitt bacteraemia score ≥4) (0% vs. 0%; P = 1.00) and defervescence (52.6% vs. 42.6%; P = 0.13) on Day 3 between the cefazolin and ESC treatment groups. Similarly, no significant differences were observed in the mean of time to defervescence (4.1 days vs. 4.9 days; P = 0.15), late clinical failure rate (18.2% vs. 10.7%; P = 0.10) and 28-day crude mortality rate (0.8% vs. 3.3%; P = 0.37) between the two groups. These data suggest that the efficacy of cefazolin is similar to that of ESCs when used as appropriate empirical antimicrobial treatment for community-onset EKP bacteraemia., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients ( n = 409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR) = 19.96; P < 0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR = 13.91; P < 0.001); bacteraemia because of pneumonia (OR = 5.45; P = 0.007); de-escalation after empirical therapy (OR = 0.28; P = 0.03); and isolates with a CTX MIC ≤ 1 mg/L (OR = 0.17; P = 0.02). Of note, isolates with a CTX MIC ≤ 8 mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC ( γ = 1.00; P = 0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC ≤ 1 mg/L. [ABSTRACT FROM AUTHOR]