Biomedical subjects

Karl J Madaras-Kelly

Publications and source records attributed to Karl J Madaras-Kelly.

5 recordsLinked to original sources

PubMed2006

Evaluation of an intervention designed to decrease the rate of nosocomial methicillin-resistant Staphylococcus aureus infection by encouraging decreased fluoroquinolone use.

OBJECTIVE: Society for Health Care Epidemiology guidelines recommend decreasing the use of fluoroquinolone antibiotics in institutions where methicillin-resistant Staphylococcus aureus (MRSA) is endemic. We evaluated whether an intervention to limit fluoroquinolone use was associated with a lower rate of nosocomial MRSA infection and summarized changes in antibiotic use, changes in other variables potentially correlated with a lower rate of MRSA infection, and rates of nosocomial infections due to other pathogens. DESIGN: Single-center quasi-experimental design. A time series of nosocomial MRSA infections was measured at monthly intervals from July 2001 through June of 2004; there were 80 MRSA infections recorded. Segmented regression analysis (ie, quasi-Poisson generalized linear models) was used to evaluate variables possibly associated with the nosocomial MRSA infection rate. SETTING: An 87-bed Veterans Affairs teaching hospital with an extended-care facility. INTERVENTION: A physician-directed computer-generated intervention designed to limit the use of fluoroquinolone antibiotics was initiated, and institutional changes in antibiotic use and nosocomial MRSA infection rates were tracked. RESULTS: After the intervention, fluoroquinolone use decreased by approximately 34%, and levofloxacin use decreased by approximately 50%. Decreased fluoroquinolone use was offset by increased cephalosporin, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole use. The nosocomial MRSA infection rate decreased from 1.37 to 0.63 episodes per 1,000 patient-days after the study intervention (P=.02). Coagulase-negative Staphylococcus and Enterococcus infection rates also decreased. However, the rate of infection with gram-negative organisms increased. The rate of MRSA infection was positively correlated with levofloxacin use (P=.01) and azithromycin use (P=.08), whereas it was negatively correlated with summer season (P=.05). In a subsequent model, the rate of MRSA infection was negatively correlated with the study intervention (P=.04). CONCLUSION: Reduction in the institutional use of fluoroquinolones may be associated with a lower nosocomial MRSA infection rate.

Cross Infection↗

PubMed2006

Experience with a clinical decision support system in community pharmacies to recommend narrow-spectrum antimicrobials, nonantimicrobial prescriptions, and OTC products to decrease broad-spectrum antimicrobial use.

BACKGROUND: Overuse of antibiotics increases the incidence of bacterial resistance and contributes avoidable costs to the health care system. OBJECTIVE: To determine the feasibility of a protocol-driven community pharmacy intervention that was designed to decrease broad-spectrum antimicrobial (BSA) use in patients with upper respiratory tract infections. METHODS: The intervention involved pharmacists who conducted guided interviews regarding patient symptoms in a cohort of patients with BSA prescription visiting 2 rural community pharmacies during peak respiratory illness season. A clinical decision support system was provided to aid in pharmacist diagnosis and assist in determining if the BSA therapy was appropriate. Upon patient consent, pharmacists attempted to contact primary care providers (PCPs) to confirm the diagnosis and recommend appropriate alternative therapy. RESULTS: There were 192 subjects with prescriptions for BSAs and symptoms of respiratory tract infection. Only 3% of the patients who were approached declined to discuss their symptoms and treatment with the pharmacist. A mean of 3 minutes was required to collect symptom and treatment information from the patients. However, when patients were asked if the pharmacist could contact their PCP to recommend alternative therapy, only 7% (n=4) of patients agreed to the intervention. The PCPs who were contacted by pharmacists were receptive to altering the BSA to first-line antimicrobial therapy such as amoxicillin or doxycycline. CONCLUSION: Despite a description of the importance of the intervention, more than 90% of patients prescribed a BSA declined to permit the community pharmacist to contact the prescriber to discuss first-line therapeutic alternatives. This experience in a pilot study to explore the feasibility of pharmacist intervention at the point of dispensing of a BSA made clear that a successful community pharmacy intervention to reduce BSA use would require an alternative method, perhaps via a collaborative practice protocol that does not require patient consent to make the drug substitution to first-line antibiotic therapy.

Anti-Bacterial Agents↗

PubMed2003

In vitro pharmacodynamic activity of gatifloxacin, gemifloxacin, moxifloxacin and levofloxacin against Streptococcus pneumoniae containing specific mutations in DNA gyrase and topoisomerase IV.

An in vitro pharmacodynatnic modeling apparatus (PDMA) generated specific bacterial kill profiles for single-dose regimens of gatifloxacin (GT), gemifloxacin (GM), moxifloxacin (MX) and levofloxacin (LV) against isolates of Streptococcus pneumoniae with specific QRDR profiles: SP-WT (no modifications); SP-C (changes in parC); and SP-AC (changes in both parC and gyrA). No differences in 3-log reduction time or total log reduction were observed among the four agents for SP-WT; however, LV failed to achieve a 3-log reduction in SP-C and SP-AC, and total log reduction after 12 hrs was minimal compared to the other agents. GM and MX required less time for 3-log reduction of SP-AC compared to GT, but total log reductions in SP-AC were similar among the three newer quinolone agents (GM > MX > GT). The study isolates with QRDR modifications greatly reduced LV activity. GM and MX maintained the greatest degree of activity against all study isolates and their activity was not adversely influenced by the genetic modifications in SP-C and SP-AC. The dual targeting characteristic of GM was also assessed, but did not offer significant advantages relative to MX and GT.

Analysis of Variance↗

PubMed2002

Pharmacodynamic characterization of efflux and topoisomerase IV-mediated fluoroquinolone resistance in Streptococcus pneumoniae.

OBJECTIVES: Most in vitro investigations of fluoroquinolone resistance involving Streptococcus pneumoniae have described genotypic changes in quinolone resistance-determining regions (QRDRs) that occur as the result of exposure to fluoroquinolones obtained with static antimicrobial concentrations. The objectives of this study were to determine whether differences exist between moxifloxacin, sparfloxacin and levofloxacin antimicrobial effect (AME) and their ability to select out stepwise mutations with wild-type, efflux-expressing and parC-mediated fluoroquinolone resistance while simulating the in vivo dosing and pharmacokinetics of the respective agents. METHODS: A one-compartment pharmacodynamic model simulated fluoroquinolone dosing regimens. Duplicate 24 h experiments were carried out in Mueller-Hinton broth with 3% horse blood at 1 x 10(8) cfu/mL. Reserpine (10 mg/L) was added to select experiments conducted with efflux-expressing strains. AME was expressed as the area under the time-concentration kill curve (AUEC24). Strains expressing increased MIC post-time-concentration kill curve (TCKC) were evaluated for changes in QRDR. RESULTS: Moxifloxacin exhibited a greater AME against all isolates. Efflux was generally associated with partial loss of AME for all fluoroquinolones, and levofloxacin retained no AME against parC-expressing S. pneumoniae. Increased fluoroquinolone MIC post-TCKC was more common with efflux expression. The addition of reserpine was associated with enhanced AME for levofloxacin and moxifloxacin, but was not associated with altered resistance selection. Isolates recovered post-TCKC from experiments involving efflux- or parC mutation-containing isolates generally exhibited a more than four-fold increase in MIC, which was associated with commonly reported substitutions in both parC and gyrA. CONCLUSION: The results of this study generally indicate that resistance selection under pharmacodynamic conditions is similar to results reported with static fluoroquinolone concentrations. While moxifloxacin AME was greater than levofloxacin and sparfloxacin, the overall selection of resistant isolates did not differ.

Anti-Infective Agents↗

PubMed2002

Clinical outcomes of ambulatory acute exacerbations of chronic bronchitis with older versus newer antimicrobials.

OBJECTIVE: To determine whether the cure rate was similar between traditional and newer antibiotics in the treatment of acute exacerbations of chronic bronchitis (AECB), to determine whether antibiotic selection during the first AECB of the season influences the frequency of subsequent AECB, and to identify variables associated with poor short- and long-term treatment outcome. METHODS: A retrospective analysis of subjects seen for management of their first seasonal AECB was conducted. Subjects were stratified into traditional therapies (n = 95) or newer therapies (n = 101) by antibiotic prescription. RESULTS: There was no difference in initial cure rates between older versus newer antibiotics (93% vs. 95%; p = 0.48). There was no difference in the number of subjects that remained AECB-free for 6 months after initial treatment with older versus newer antibiotic regimens (34% vs. 28%; p = 0.37). Oxygen initiation or increased dose (OR 10.9; 95% CI 1.4 to 84.2; p = 0.02) was the only variable independently associated with lack of AECB resolution. Nonsmoking status trended toward an association with remaining AECB-free at 180 days (OR 0.39; 95% CI 0.15 to 1.01; p = 0.053). CONCLUSIONS: The use of older versus newer antibiotics did not independently predict short-term outcome or future AECB.

Acute Disease↗