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John A Bosso

Publications and source records attributed to John A Bosso.

14 recordsLinked to original sources
PubMed2006

Consequences of combining cystic fibrosis- and non-cystic fibrosis-derived Pseudomonas aeruginosa antibiotic susceptibility results in hospital antibiograms.

BACKGROUND: In preparing hospital antibiograms for individual organisms and antibiotics, laboratories often combine susceptibility data for isolates from a variety of sources and patient types. If results from patients with known resistance patterns that vary from normal are included, the overall susceptibility value for the institution could be misleadingly skewed. OBJECTIVE: To assess the degree of bias introduced into a hospital antibiogram by combining cystic fibrosis (CF) and non-CF isolates of Pseudomonas aeruginosa to produce one hospital-wide percent susceptible figure for each tested antibiotic. METHODS: A retrospective analysis was conducted of an academic, tertiary care medical center's microbiology database. We examined quarterly and annual susceptibility data from 2004, comparing non-CF data with combined susceptibility data for 10 antibiotics within each quarter, as well as those reported in the annual antibiogram. Differences were assessed for statistical significance using chi(2) testing with Bonferroni correction. RESULTS: Large differences were observed between non-CF and combined percent susceptible data in the 4 quarters (aminoglycosides 3% vs 20%, fluoroquinolones 2% vs 18%, respectively) and when comparing annual non-CF (n = 191) with annual combined (n = 266) data. With the annual figures, these differences were frequently statistically significant (70% vs 58%, 91% vs 83%, 85% vs 70%, and 72% vs 60% for gentamicin, tobramycin, amikacin, and gatifloxacin/levofloxacin, respectively; all p< or =0.01). CONCLUSIONS: Combining CF and non-CF P. aeruginosa susceptibility into one percent susceptibility value for all isolates may produce figures that underestimate the activity of some antibiotic classes against non-CF isolates. Clinicians may make less than optimal empiric antibiotic selection choices based on such data.

Anti-Bacterial Agents↗
PubMed2006

Using interrupted time series analysis to assess associations of fluoroquinolone formulary changes with susceptibility of gram-negative pathogens and isolation rates of methicillin-resistant Staphylococcus aureus.

The use of fluoroquinolones has been linked to increasing bacterial resistance and infection and/or colonization with already resistant pathogens both as a risk factor and based on volume of use. Changes in individual fluoroquinolones used in an institution may also be related to these clinical problems. Interrupted time series analysis, which allows for assessment of the associations of an outcome attributable to a specific event in time, was used to study the effect of changes in our hospital's fluoroquinolone formulary on fluoroquinolone susceptibility rates in select gram-negative pathogens and the methicillin-resistant Staphylococcus aureus (MRSA) isolation rate. Susceptibility rates to ciprofloxacin were considered for the period of 1993 through 2004, while the MRSA isolation rate was assessed from 1995 through 2004. Levofloxacin was added to the formulary in 1999, and gatifloxacin was substituted for levofloxacin in 2001. Statistically significant changes in the already declining rates of susceptibility of Pseudomonas aeruginosa (P, 0.042) and Escherichia coli (P, 0.004) to ciprofloxacin and in the already rising MRSA isolation rate (P, 0.001) were associated with the addition of levofloxacin to the formulary. Substitution of gatifloxacin for levofloxacin on the formulary was associated with reversals in the downward trend in E. coli susceptibility to ciprofloxacin and the upward trend in MRSA isolation rate. No associations were detected on susceptibility of Klebsiella pneumoniae or Proteus mirabilis to ciprofloxacin. These findings suggest that potential changes in susceptibility to fluoroquinolones and isolation of MRSA may vary by both drug and organism.

Anti-Bacterial Agents↗
PubMed2005

The antimicrobial armamentarium: evaluating current and future treatment options.

The development and introduction of new antibiotics has, unfortunately, not kept pace with the development of bacterial resistance, and the need for new agents is becoming acute. Although some currently marketed agents remain valuable tools in the treatment of infectious diseases, few new drugs have reached the market in the last decade. In recent years, antibiotics with activity against certain problematic resistant bacteria such as methicillin-resistant Staphylococcus aureus, including linezolid and daptomycin, have been approved for clinical practice. Recently, tigecycline, a minocycline derivative, received approval by the United States Food and Drug Administration for treatment of complicated skin and skin structure and intraabdominal infections; the agent is also active against a variety of multidrug-resistant bacteria. Of the other agents in phase III development, ceftobiprole--a cephalosporin, and faropenem and doripenem--both carbapenems, have wide antibacterial spectra. Antimicrobial agents in the pipeline with marked gram-positive activity include dalbavancin, telavancin, and oritavancin.

Anti-Bacterial Agents↗
PubMed2004

Linezolid pharmacokinetics in adult patients with cystic fibrosis.

The pharmacokinetics of many drugs are altered in patients with cystic fibrosis (CF), often necessitating different dosage requirements than those used in non-CF patients. The objective of this study was to determine the pharmacokinetics of linezolid, an antibiotic with good activity against gram-positive organisms such as methicillin-resistant Staphylococcus aureus, in patients with CF so that dosage requirements could be established. Twelve adult patients (6 male) ranging in age from 22 to 39 years were studied. A single 600-mg dose was administered intravenously over 0.5 h, and plasma samples were collected at 0 (predose), 0.5, 0.75, 1, 2, 4, 8, and 24 h. Linezolid concentrations were determined with a validated high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using standard noncompartmental methods. Blood chemistry and hematologic indices were determined before and after the study for safety purposes. All patients completed the study without encountering any adverse reactions. The pharmacokinetic parameters, while variable, with half-lives varying from 1.76 to 8.36 h, were similar to those previously described in other populations. Mean (+/- standard deviation) values for pharmacokinetic parameters of interest were as follows: elimination rate constant, 0.21 (0.11) h(-1); half-life, 4.41 (2.43); volume of distribution at steady state, 0.87 (0.19) liters/kg of body weight; and total body clearance, 0.12 (0.06) liters/h/kg. No patient would have achieved the pharmacodynamic target of an area under the concentration-time curve/MIC ratio of 83 h for pathogens for which the MIC was 4 micro g/ml. Patients with inadequate clinical responses to linezolid may require more frequent dosing.

Acetamides↗
PubMed2004

The impact of antibiotic management on resistance.

The misguided presumption that a simple inverse relationship exists between the use of antibiotics and the emergence of bacterial resistance (i.e., increasing antibiotic use equals decreasing susceptibility and vice versa) has handicapped a full understanding of this relationship and perhaps efforts to bring resistance under control. In fact, this relationship is complicated. This article reviews factors that obscure detection of associations between antibiotic use and the emergence of resistance. It also provides a sample of the extensive data on this subject in the hope of encouraging the conduct of more sophisticated studies of the relationship between antibiotic use and the emergence of resistance. Such studies are necessary to provide institutions with the data they need to make informed decisions regarding antibiotic use.

Anti-Bacterial Agents↗
PubMed2003

Assessment of differences in antimicrobial effect determined with two in vitro pharmacodynamic models: impact of surface area to volume ratio.

STUDY OBJECTIVE: To measure the influence of different surface area:volume ratios (SA:Vs) on antibiotic penetration and subsequent antibacterial effect. DESIGN: In vitro laboratory experiment. SETTING: Two academic research laboratories. INTERVENTION: The two models with effective SA:Vs of 5.34 and 4.80 cm(-1) were evaluated by conducting a time-kill experiment with Pseudomonas aeruginosa ATCC 27853 and ceftazidime. MEASUREMENTS AND MAIN RESULTS: Ceftazidime was administered by constant infusion into the central compartment. Its penetration into the peripheral compartment and bacterial counts were determined over 24 hours, and antibacterial effect was quantified. Antibiotic penetration, calculated using central compartment and peripheral compartment area under the concentration-time curves, and effect, quantified as the relationship between the areas under growth and kill curves, differed between the models. Antibiotic penetration into the peripheral compartment was 53% greater over the first 4 hours of the experiment in the model with the larger SA:V. This was associated with antibacterial effects that were 64% and 38% greater in the 0-4-hour and 0-24-hour time periods, respectively. CONCLUSION: Differences in antibiotic penetration and effect observed between these models are likely explained by differences in SA:V

Anti-Bacterial Agents↗
PubMed2003

A novel method of estimating cost of therapy by using patient population characteristics: analysis of fluoroquinolones in various populations with different distributions of renal function.

INTRODUCTION: Formulary decisions regarding a given drug class are often made in the absence of patient outcome and/or sophisticated pharmacoeconomic data. Analyses that consider factors beyond simple acquisition costs may be useful in such situations. For example, the cost implications of using manufacturers' recommendations for dosing in patients with renal dysfunction may be important, depending on the distribution of various levels of renal function within a patient population. METHODS: Using four 1000-patient populations representing different renal function distributions and a fifth population of our medical center's distribution, we determined the costs of therapy for intravenous and oral levofloxacin, gatifloxacin, and moxifloxacin for a 10-day course of therapy for community-acquired pneumonia. Costs considered were average wholesale prices (AWPs), 50% of AWP, or same daily price, plus intravenous dose preparation and administration costs when applicable. Costs for each renal function distribution were examined for significant differences with an analysis-of-variance test. Also, costs of failing to adjust dosing regimens for decreased renal function were determined. RESULTS: Differences in fluoroquinolone costs (AWP, 50% AWP, or when matched as the same daily price) among the populations were found. When considering same daily prices, differences among populations ranged from about 35,000 dollars with intravenous gatifloxacin to more than 51,000 dollars for intravenous levofloxacin (all fluoroquinolones, p>0.05). Within a population, differences in costs among the intravenous fluoroquinolones ranged from 47,000-99,000 dollars. Rank orders of the drugs and population costs of therapy were affected by the pricing structure used and varied by the specific population and drug. Differences among the fluoroquinolones or populations were much smaller (<2100 dollars) when considering oral regimens. Costs potentially incurred by failing to adjust dosing for renal function were substantial. CONCLUSION: Formulary decisions can be facilitated by considering factors such as patient characteristics and related dosing in addition to simple acquisition costs. In our example, consideration of the distribution of renal function within a given patient population and related dosing for these fluoroquinolones revealed potentially important differences within the class.

Administration, Oral↗
PubMed2002

Comparative activity of gatifloxacin and other antibiotics against 4009 clinical isolates of Streptococcus pneumoniae in the United States during 1999-2000.

The susceptibility of 4009 recent clinical isolates of Streptococcus pneumoniae to gatifloxacin, levofloxacin, ciprofloxacin, penicillin, ceftriaxone and azithromycin was determined. Overall rates of susceptibility to these agents were 99.4, 98.7, 71.2, 55.2, 80.9, and 71.3%, respectively. Resistance to all tested agents was associated with penicillin resistance. Of penicillin nonsusceptible isolates, 36% were resistant. Resistance to the fluoroquinolones was unusual and gatifloxacin generally appeared to be four-fold more active than levofloxacin or ciprofloxacin. Multidrug resistant S. pneumoniae accounted for 6.2% of this sample. The lowest rate of susceptibility to non-fluoroquinolone antibiotics was observed in isolates from the South region of the United States, which appeared to be explained by both the proportion of and the inherently higher MICs of certain types of isolates.

Adolescent↗
PubMed2002

Comparison of methods of interpretation of checkerboard synergy testing.

Four different methods for interpreting the results of checkerboard synergy testing were compared by applying each to a set of synergy study data. Statistically significant differences in synergy were detected among methods (% synergy ranged from 10 to 83%). As interpretations were found to vary widely based upon method, one should be aware of this in interpreting the relevant literature.

Acinetobacter baumannii↗
PubMed2002

Determination of antibiotic effect in an in vitro pharmacodynamic model: comparison with an established animal model of infection.

Animal infection models have historically been used to study pharmacodynamic relationships. Similar results could theoretically be produced by using an in vitro pharmacodynamic model as an alternative to animal models. We compared the antibiotic effects of ticarcillin administered in various doses and dosing regimens against Pseudomonas aeruginosa ATCC 27853 under conditions analogous to those previously employed in a neutropenic-mouse thigh infection model (B. Vogelman et al., J. Infect. Dis. 158:831-847, 1988). Ticarcillin dosages of either 96, 192, or 384 mg/day were administered at 1-, 2-, 3-, 4-, 8-, 12-, or 24-h intervals into a two-compartment model in order to duplicate the concentration-time profiles of the animal model. Colony counts were enumerated at 0 and 24 h. Linear regression and sigmoidal maximum-effect (Emax) model fitting were used to assess the relationship between the percentage of time that the concentration remained above the MIC (%T>MIC) or above four times the MIC (%T>4xMIC) and the change in the log(10) CFU per milliliter (Deltalog(10) CFU/ml) in the central and peripheral compartments. Statistical analysis of the Deltalog(10) CFU/ml values was performed for matched regimens of the in vitro and animal models based on the %T>MICs. The slopes of the regression equations of %T>MICs relative to Deltalog(10) CFU/ml values were similar for the in vitro and animal models, but the y intercept was greater with the in vitro model. The Deltalog(10) CFU/ml values of the 0- to 24-h colony counts at equivalent %T>MICs in the two models were not statistically different (P = 0.087). Overall, the peripheral compartment of the in vitro model was a better predictor of effect than the central compartment. This study, which compares pharmacodynamic principles between an in vitro and an animal model, demonstrated similar relationships between %T>MICs and effects.

Animals↗
PubMed2002

Differences in antimicrobial drug exposure in patients with various degrees of renal function based on recommendations from dosing references.

STUDY OBJECTIVE: To calculate and compare 24-hour area under the unbound drug concentration-time curves (AUC(0-24)) of antimicrobials with dosing recommendations from six commonly used dosing references. INTERVENTION: Unbound plasma concentration-time profiles of 13 antimicrobial agents (4 penicillins, 3 cephalosporins, 2 carbapenems, aztreonam, 3 fluoroquinolones) were simulated at steady state using a one-compartment open model for a 70-kg adult based on pharmacokinetic parameters obtained from peer-reviewed literature. Simulations were performed at five levels of creatinine clearance (Cl(cr)). MEASUREMENTS AND MAIN RESULTS: Differences in AUC(0-24) for each antimicrobial agent were noted among the six references at each level of Cl(cr) as well as within references across the range of Cl(cr). In addition, up to 16-fold and 3-fold ranges in AUC(0-24) values were observed for beta-lactams and fluoroquinolones, respectively, in one reference based on dosing recommendations at a single level of Cl(cr) (due to more than one dose and/or dosing interval). CONCLUSION: Clinicians should be aware of differences among common references when selecting dosages of antimicrobial agents, especially for patients with moderate-to-severe renal impairment.

Adult↗