Effect of Differences in MIC Values on Clinical Outcomes in Patients with Bloodstream Infections Caused by Gram-Negative Organisms Treated with Levofloxacin (original) (raw)
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F1000 - Post-publication peer review of the biomedical literature, 2009
Emerging evidence suggests that current fluoroquinolone dosing strategies may be inadequate to treat bloodstream infections caused by organisms classified as sensitive. This study sought to determine if differences in MICs for levofloxacin-susceptible gram-negative organisms correlate with differences in patient outcomes. A retrospective cohort study evaluated patients treated with levofloxacin for bloodstream infections caused by susceptible gram-negative organisms. Patients infected with gram-negative organisms for which MICs indicated susceptibility were categorized into three groups: those with organisms for which MICs were low (<0.25 mg/liter), intermediate (0.5 mg/liter), and high (1 or 2 mg/liter). Patients were evaluated for baseline similarity, all-cause mortality, and measurements of morbidity. A total of 404 patients with bloodstream infections caused by gram-negative organisms were identified. Of these patients, 312 were treated with levofloxacin and included in the analysis. No significant difference in all-cause mortality among the three groups was observed. The high-MIC group had a significantly longer average hospital stay postculture than the low-and intermediate-MIC groups (16.4 days versus 7.3 and 7.9 days; P < 0.01) and a significantly longer duration of infection (2.1 days versus 1.0 and 1.2 days; P < 0.001). Multivariate analysis adjusting for covariates revealed that a high MIC was associated with an increase of 5.67 days (95% confidence interval, 0.77 to 10.62 days; P ؍ 0.02) in the mean length of stay postculture compared to the mean length of stay for the low-MIC group. Patients treated with levofloxacin for bloodstream infections caused by gram-negative organisms for which MICs were elevated, yet still in the susceptible category, had worse outcomes than similar patients infected with organisms for which MICs were lower. In vitro susceptibility classifications of fluoroquinolones for the treatment of bloodstream infections caused by gram-negative organisms require further study.
Antimicrobial Agents and Chemotherapy, 2012
The objective of this study was to analyze the impact of MIC values within the susceptible range of antibiotics on the outcomes of patients with Gram-negative infections. The PubMed and Scopus electronic databases were searched. We identified 13 articles (1,469 patients) that studied the impact of antibiotic MICs on the outcomes of infections; β-lactams were studied in 10 of them. Infections due to Salmonella enterica strains with high fluoroquinolone MICs were associated with more treatment failures than those due to strains with low MICs (relative risk [RR], 5.75; 95% confidence interval [CI], 1.77 to 18.71). Among non- Salmonella enterobacteriaceae, there was no difference in treatment failures depending on the MIC value (RR, 1.18; 95% CI, 0.71 to 1.97); however, a higher all-cause mortality was observed for patients infected with strains with high MICs (RR, 2.03; 95% CI, 1.05 to 3.92). More treatment failures were observed for patients infected with nonfermentative Gram-negative...
Clinical Infectious Diseases, 2003
We retrospectively examined the relationship between fluoroquinolone use and the susceptibilities of 11 bacterial pathogens to fluoroquinolones in 10 US teaching hospitals from 1991 through 2000. Statistical significance was determined by 2-way analysis of variance, with the number of isolates tested each year as a weighting factor. The analysis of baseline-to-end point change in the percentage of susceptibility and the slope of the regression line (trend line) for logit percentage of susceptibility showed that the overall percentage of susceptibility to fluoroquinolones decreased significantly during the study period ( ) and that change in P ! .05 percentage of susceptibility was significantly related to change in fluoroquinolone use ( ). Particularly P ! .05 notable were the decreases in the susceptibilities of Pseudomonas aeruginosa, Proteus mirabilis, and Escherichia coli (decreases of 25.1%, 11.9%, and 6.8%, respectively).
Mortality and Length of Stay in Patients with Bloodstream Infections Due to Drug-Susceptible Versus Drug-Resistant Gram-Negative Bacteria, 2019
A prospective patient surveillance and analysis in three urban hospitals with the objective of comparing the mortality rates among patients with antimicrobials-sensitive versus-resistant gram-negative bacterial bloodstream infections. The analysis focused on the rates of in-hospital and 28-days mortality. There were 189 patients with BSI, drug-susceptible gram-negative bacteria (DSGNB) 40.7%, multi-drug resistant bacteria (MDRGNB) 42.3% and extensive-drug resistant bacteria (XDRGNB) 16.9%. The mean age, gender, SOFA score on the initial evaluation, APACHE II score, comorbidities, identified bacterial species, and BSI-associated diagnoses were not statistically different except for VAP (P = 0.000) in the XDRGNB infected patients. In-hospital and 28-days mortalities were significantly higher in the XDRGNB-BSI group (P = 0.000), and ICU length of stay (P = 0.000). XDRGNB-BSI was significantly higher in inappropriate and delayed treated patients (P < 0.05). Logistic regression analysis demonstrated no significant interaction for the 28 days mortality neither with the admission diagnoses, the antimicrobial class (except aminoglycosides), the comorbidities (except for solid tumors) (P > 0.05, Nagelkerke R 2 < 0.4). In conclusion, BSI due to multiple class antimicrobial resistance has higher mortality and ICU length of stay.
BMC Infectious Diseases, 2013
Background: Infections are a common cause of morbidity and mortality in patients with acute myeloid leukemia (AML). The evidence for efficacy of antibiotic prophylaxis in reducing the mortality rates and the incidence of bacterial infections was also reported by a systematic review published by Cochrane in 2012. The objective of our study was to report the incidence and the etiology of bloodstream infections in patients with AML undergoing levofloxacin prophylaxis during neutropenic episodes.
Antibiotics, 2020
Objectives: Chromosomally mediated AmpC-producing Enterobacteriaceae (CAE) display high susceptibility to fluoroquinolones; minimal clinical data exist supporting comparative clinical outcomes. The objective of this study was to compare treatment outcomes between fluoroquinolone and nonfluoroquinolone definitive therapy of bloodstream infections caused by CAE. Methods: This retrospective cohort assessed adult patients with positive blood cultures for CAE that received inpatient treatment for ≥48 h. The primary outcome was difference in clinical failure between patients who received fluoroquinolone (FQ) versus non-FQ treatment. Secondary endpoints included microbiological cure, infection-related length of stay, 90-day readmission, and all-cause inpatient mortality. Results: 56 patients were included in the study (31 (55%) received a FQ as definitive therapy; 25 (45%) received non-FQ). All non-FQ patients received a beta-lactam (BL). Clinical failure occurred in 10 (18%) patients, wit...
This study aimed at evaluating the efficacy of four common fluoroquinolone drugs over a year period on some clinical isolates. It also aimed at comparing statistically the average effects of each drug on the isolates. Five different clinical samples (urine, sputum, wound, blood and high vaginal swab [HVS]) from patients attending a university medical centre (between June 2011 and May 2012) were analysed for the purpose of bacteria isolation. The isolates were tested with commonly used flouroquinolones: pefloxacin (30 µg), ofloxacin (30 µg), sparfloxacin (10 µg), and ciprofloxacin (10 µg). Each sensitivity test was done in duplicate and a mean average of zone of inhibition was recorded. One hundred and eighty eight bacteria were isolated: Staphylococcus aureus (44.7%), Streptococcus pyogenes (6.4%), Escherichia coli (28.2%), Pseudomonas aeruginosa (8.5%), Klebsiella pneumonia (8.0%), and Proteus mirabilis (4.3%). All drugs were equally potent against the isolates, but a higher potency was seen in ofloxacin against P. mirabilis. The fluoroquinolones are a group of broad spectrum drugs effective in clinical cases. Their efficacy should be preserved by ensuring strict compliance to local drug policies.
WIN 57273, a new fluoroquinolone with enhanced in vitro activity versus gram-positive pathogens
Antimicrobial Agents and Chemotherapy, 1990
WIN 57273 is a new fluoroquinolone with excellent in vitro activity versus gram-positive pathogens, including methicillin-susceptible and-resistant Staphylococcus aureus and Staphylococcus epidermidis and gentamicinsusceptible and-resistant Enterococcus faecalis. We compared the microdilution MICs and MBCs of this compound to those of other antimicrobial agents for more than 30 clinical isolates of each of these groups of organisms and found that with few exceptions, it was at least 10 times more active than al other drugs tested. Selection for resistance to ciprofloxacin (.5 gLg/ml) or WIN 57273 (>0.16 ,ug/ml) by the gradient plate method produced mutants with diminished susceptibility to the other fluoroquinolone; however, the MICs and MBCs of WIN 57273 for such strains were still quite low and remalned below the preliminary susceptibility breakpoint (s2 gg/ml). Spontaneous mutations conferring resistance to two and five times the WIN 57273 MIC were detectable at low frequencies for S. aureus and S. epidermidis; such mutations were virtually undetectable for E. faecalis. Further testing is necessary to establish if the effectiveness of WIN 57273 is maintained in vivo, first in animals and then in humans with infections caused by methicillin-susceptible and-resistant strains of S. aureus and S. epidermidis or gentamicin-susceptible and-resistant strains of E. faecalis. * Corresponding author. MATERIALS AND METHODS Antimicrobial agents. WIN 57273 was supplied by Sterling-Winthrop Research Institute (Rensselaer, N.Y.). All other antimicrobial agents were obtained from their manufacturers and included ampicillin, nafcillin, imipenem, cefazolin, daptomycin, vancomycin, gentamicin, rifampin, ciprofloxacin, and ofloxacin. Bacterial strains. The organisms used in this study were clinical isolates obtained mainly from the Detroit, Mich.., area. Some strains of E.. faecalis originated in New Haven, Conn. The methicillin susceptibility of staphylococci was determined by the oxacillin disk method (6). The gentamicin susceptibility or resistance of strains of E. faecalis was established by the method of Zervos et al. (13). Organisms used for quality assurance included S. aureus ATCC 29213 and E. faecalis ATCC 29212. Determination of MICs and MBCs. MICs for an inoculum