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Abstract Background: The prevalence of glucose abnormalities has been reported to be greater in hospitalized patients receiving gatifloxacin than in patients receiving ceftriaxone. Objective: The ...purpose of the current study was to identify risk factors for hyperglycemia in hospitalized patients receiving gatifloxacin. Methods: This retrospective, nested case-controlled study was conducted in 69 patients and 69 controls in 2 nonteaching hospitals in Houston, Texas. Classification and regression tree (CART) analysis was conducted to identify break points in continuous variables. Univariate and multivariate logistic regression analyses were also performed. Results: A total of 138 patients (mean SD age, 68.3 17.3 years; weight, 77.4 21.1 kg; sex, women/ men, 69.6%/30.4%; race Hispanic, 58.3%; white, 28.5%; black, 9.2%; other, 4.0%) were identified. Patients who developed hyperglycemia (blood glucose level >200 mg/dL) within 72 hours of gatifloxacin ad-ministration (cases) were matched 1:1 with patients who received gatifloxacin for ≥5 days and did not experience hyperglycemia during treatment and for 3 days after the end of treatment (controls). In univariate analysis, cases were more likely than controls to have diabetes (89.9% vs 13.0%; P < 0.001), have a decreased mean (SD) creatinine clearance (CrCl) (53.8 36.8 vs 69.2 45.3 mL/min; P = 0.025), be located in the intensive care unit at the time of the event (20.3% vs 7.2%; P = 0.02), have received gatifloxa-cin doses higher than recommended based on renal function (>200 mg/d when CrCl <40 mL/min) (25/69 36.2% vs 9/69 13.0%), have leukocytosis (mean SD white blood cell WBC count, 15.5 7.4 vs 12.8 6.2 cells/mm3), and have received concomitant total parenteral nutrition (7/69 10.1% vs 0 0%; P = 0.02) and/or steroids (22/69 31.9% vs 8/69 11.6%; P = 0.008). CART analysis identified age >65 years, albumin <3.2 g/dL, WBC count >14.5 cells/mm3, and CrCl <40 mL/min to be more common in hyperglycemic patients. In logistic regression, diabetes (odds ratio OR = 233; 95% CI, 19-2784) and excessive dose for renal function (OR = 42; 95% CI, 2-770) were identified as independent predictors for hyperglycemia in patients receiving gatifloxacin. After controlling for diabetes, concomitant steroids (OR = 5.7; 95% CI, 1.5-21.1) and excessive dose for renal function (OR = 4.9; 95% CI, 1.2-20.4) were associated with hyperglycemia in patients receiving gatifloxacin. Conclusions: This retrospective, nested case-controlled study found that the risk of hyperglycemia increased in diabetic patients who received concomitant steroids or higher gatifloxacin doses than recommended by the manufacturer's prescribing information. The application of these data should be assessed for other fluoroquinolones used at higher doses.
Abstract
Background
Current guidelines recommend vancomycin (VAN) dosing to achieve AUC/MIC ratio ≥400 for patients (pts) with serious MRSA bloodstream infections (BSI), but supporting data were ...largely derived in single center retrospective studies. A recent study using a Bayesian approach to estimate the VAN AUC found that patients with MRSA BSI who had an AUCDAY2/MICBMD ≥ 650 or an AUCDAY2/MICETEST ≥ 320 had lower incidences of failure (Clin Infect Dis 59:666, 2014). This study prospectively evaluated if these VAN AUCDAY2/MIC targets were associated with lower incidences of failure (PROVIDE, Award number UM1AI104681, Antibacterial Resistance Leadership Group).
Methods
Prospective, multi-center (n = 14), observational study (2014–2106) of hospitalized adults with confirmed MRSA BSI treated with VAN ≥ 72h. Exclusion: (1) neutropenia; (2) cystic fibrosis; (3) renal replacement therapy; (4) APACHE-II score > 25; (5) previous MRSA BSI within 60 days. VAN exposures were estimated using maximum a posteriori probability procedure in ADAPT 5. MICBMD and MICETEST were performed at a central laboratory. Outcomes: failure (30-day mortality or MRSA BSI ≥ 7 days); acute kidney injury (AKI), ≥1.5 × increase in serum creatinine (Scr) among patients with a baseline SCR < 2.0mg/dl. The study was powered at 80% to detect a 17.5% difference in failure between AUCDAY2/MIC groups.
Results
Among the 265 evaluable patients, mean (SD) age was 61 (17) and APACHE-II was 12 (6). Endocarditis was definite/possible in 29%. The MIC50/90 by BMD and ETEST were 1/1 and 1.5/1.5mg/l, respectively. Failure occurred in 18%; 26% had AKI. Mean (SD) VAN duration was 18 (14) days. Mean (SD) AUCDAY2 was 586.9 (235.5) and 44% and 73% of patients achieved an AUCDAY2/MICBMD ≥ 650 and AUCDAY2/MICETEST ≥ 320. In the multivariate analyses (Figure 1), failure was not significantly different between AUCDAY2/MIC groups. In contrast, AKI was significantly more common in patients with an AUCDAY2/ MICETEST > = 320.
Conclusion
Achievement of higher VAN AUCDAY2/MIC exposures for patients with MRSA BSIs were not associated with better outcomes and were found to result in increased AKI. Clinicians should assess the benefits vs. risks of using VAN regimens that confer high AUCDAY2/MIC exposures for patients with MRSA BSIs.
Disclosures
T. P. Lodise Jr., allergan: Consultant, Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; medicines company: Consultant, Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium; melinta: Consultant, Consulting fee; motif: Consultant and Scientific Advisor, Consulting fee; paratek: Consultant and Scientific Advisor, Consulting fee; nabriva: Consultant, Consulting fee; M. J. Zervos, Merck, Inc.: Investigator, Research grant; M. Scheetz, Bayer: Scientific Advisor, Consulting fee; V. Fowler Jr., Pfizer, Novartis, Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Cubist, Basilea, Affinergy, Janssen, xBiotech, Contrafect: Consultant, Consulting fee; NIH, Basilea, MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius: Grant Investigator, Research grant; Green Cross, Cubist, Cerexa, Durata, Theravance; Debiopharm: Consultant, Consulting fee; UpToDate: author on several chapters, Royalties
Study Objectives. To compare rates of hypoglycemia and hyperglycemia among elderly hospitalized patients with normal blood glucose concentrations at baseline who were receiving either gatifloxacin or ...levofloxacin, and to determine if appropriateness of their doses, according to their package inserts, was associated with hypoglycemia or hyperglycemia.
Design. Retrospective cohort study.
Setting. Integrated Veterans Administration (VA) health care system.
Patients. Nine hundred thirty‐seven elderly (≥ 65 yrs) patients with documented blood glucose levels of 65–140 mg/dl before receiving a fluoroquinolone.
Measurements and Main Results. Between January 2003 and April 2004, 405 patients receiving levofloxacin met study criteria. In April 2004, gatifloxacin was substituted for levofloxacin on the formulary of this VA system. Thus, between April 2004 and December 2004, 532 patients received gatifloxacin. All blood glucose concentrations during hospitalization that were measured during fluoroquinolone therapy or within 72 hours of completion of therapy were reviewed. Demographic characteristics, comorbidities, insulin and oral hypoglycemic therapies, disease severity, blood glucose levels, and outcomes were recorded and compared between groups. The two groups were similar at baseline for all characteristics examined except previous hospitalization. In the logistic regression, gatifloxacin was independently associated with both hypoglycemia (adjusted odds ratio AOR 2.5, 95% confidence interval CI 1.2–5.7, p=0.04) and hyperglycemia (AOR 2.4, 95% CI 1.5‐3.6, p<0.001). Improper dosage adjustment based on renal function was not associated with higher rates of hypoglycemia and hyperglycemia for either drug. Of the 532 patients receiving gatifloxacin, 465 (87.4%) received appropriate doses, yet gatifloxacin was associated with higher rates of hypoglycemia and hyperglycemia compared with patients receiving levofloxacin.
Conclusions. Higher rates of both hypoglycemia and hyperglycemia were noted among elderly hospitalized patients who received gatifloxacin compared with those receiving levofloxacin, irrespective of dosing.
Antimicrobial research has hit a wall: treatment discoveries are rarer and resistant pathogen strains more prevalent. Rather than infection control itself, antimicrobial stewardship is an essential ...measure in ensuring management of hospital-acquired infections. Throughout this book, international experts discuss all angles of stewardship.
In the case of First English Evangelical Lutheran Church of Glendale versus County of Los Angeles, the US Supreme Court held that, under the 5th Admendment takings clause, a landowner must be ...compensated for the effect of a regulation from the time it was first imposed until the time the government rescinds it. However, in order to determine whether this decision is appropriate, the appropriate objectives for a system of takings compensation must be identified. Further, how effectively possible candidates take into account the nature of the interests at stake also should be determined. An examination of the objectives and nature of the interests indicates that economic efficiency does not justify the Court's decision. While an argument in favor of landowners may be appealing, expanding the government's liability may result in less land use regulation or more expensive land use regulation, which would ultimately result in higher taxes.
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