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1.  Lack of Change in Susceptibility of Pseudomonas aeruginosa in a Pediatric Hospital Despite Marked Changes in Antibiotic Utilization 
It is assumed that a direct relationship exists between the extent of use of any given antibiotic or antibiotic class and the degree of susceptibility or resistance on the part of various bacteria to that antibiotic or class.
Pseudomonasaeruginosa susceptibility rates and utilization of key antipseudomonal antibiotics in a pediatric hospital, reflected as grams/1,000 patient days, were studied over a 7-year period.
While the volume of use of a number of antibiotics changed dramatically over this time period, susceptibility of Pseudomonas to these same agents remained relatively stable. The use of aminoglycosides decreased 14.5% while that of piperacillin/tazobactam increased 92% over the period of observation while susceptibility generally varied by <10%.
Contrary to popular belief, changes in antibiotic utilization patterns do not always result in changes in susceptibility thus emphasizing the importance of continual institutional monitoring of antibiotic use and susceptibility patterns.
Electronic supplementary material
The online version of this article (doi:10.1007/s40121-014-0028-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4108119  PMID: 25134812
Antibiotic utilization; Infectious disease; Pediatrics; Pseudomonas aeruginosa; Susceptibility
2.  Stable Susceptibility to Aminoglycosides in an Age of Low Level, Institutional Use 
Infectious Diseases and Therapy  2013;2(2):209-215.
The use of aminoglycosides has decreased dramatically over several decades in the United States due to the introduction of safer Gram-negative agents. This study was conducted to assess possibly changing aminoglycoside susceptibility rates between 2006 and 2012 and in reference to 1992 use in the context of aminoglycoside use volume.
Quarterly adult use of amikacin, gentamicin and tobramycin were determined from the Medical University of South Carolina Medical Center, Charleston, South Carolina, USA, pharmacy drug use database and expressed as total aminoglycoside defined daily doses per 1,000 patient days for the years 1992 and 2006 through 2012. Annual susceptibility of Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, for the years 1992, 2006, and 2008 through 2012 were retrieved from our hospital’s clinical microbiology database (duplicate isolates were excluded). Quarterly and annualized aminoglycoside usage rates were compared to the other years of interest. Likewise, susceptibility rates of the target organisms to each aminoglycoside were also compared across the same timeframe.
While total use of aminoglycosides decreased slightly from 1992 to 2006, it increased by about 40% between 2006 and 2008 and then stabilized. Changes in susceptibility rates between 1992 and 2006 were all ≤±9% with the exception of K. pneumoniae susceptibility to amikacin (−17%). Changes in susceptibility from 1992 to 2012 were also all ≤±9%. Tobramycin remained the most active versus P. aeruginosa (% susceptible = 90), while amikacin remained most active versus E. coli and K. pneumoniae (% susceptible = 98 and 98, respectively).
With low level use of aminoglycosides in our institution over the past 2 decades, the susceptibility of key Gram-negative pathogens has remained relatively stable, preserving these agents as potential alternative therapies as resistance arises to other frequently used antibiotics.
PMCID: PMC4108105  PMID: 25134483
Amikacin; Aminoglycosides; Antibiotic usage; Antibiotic resistance; Escherichia coli; Gentamicin; Infectious diseases; Klebsiella pneumoniae; Pseudomonas aeruginosa; Tobramycin
3.  Comparison of Hospitalwide and Custom Antibiograms for Clinical Isolates of Pseudomonas aeruginosa 
Hospital Pharmacy  2013;48(4):295-301.
Hospital antibiograms, which are commonly used to determine empiric antibiotic therapy and as a tool in stewardship in a given institution, are open to bias when combining susceptibility results from various sources, hospital locations, and patient groups.
We assessed such differences, using Pseudomonas aeruginosa as a test case, with susceptibility data from 2008 through 2010 in our institution. Each year’s data were analyzed separately. A variety of specific or subcategorical antibiograms were compared with each other as well as with versions including all tested isolates and those with results from inpatients and outpatients only. Statistical significance was determined at the .01 level using either chi-square or Fisher exact test, and clinical significance was defined as ≥10 percentage points.
A variety of clinically significant differences were found that illustrated important differences within the intensive care unit environment and based on population, specifically adult versus pediatric. Concordance between statistically significant and clinically significant differences was poor.
These results corroborate and extend previous similar observations and point to the potential importance of subanalyses in preparing the annual hospital antibiogram.
PMCID: PMC3839458  PMID: 24421478
antibiogram; antibiotic; bacterial susceptibility
5.  AACP Strategy for Addressing the Professional Development Needs of Department Chairs 
Objectives. Characterize the skills and abilities required for department chairs, identify development needs, and then create AACP professional development programs for chairs.
Methods. A 30-question electronic survey was sent to AACP member department chairs related to aspects of chairing an academic department.
Results. The survey identified development needs in the leadership, management, and personal abilities required for effective performance as department chair. The information was used to prioritize topics for subsequent AACP development programs. Subsequent programs conducted at AACP Interim and Annual Meetings were well attended and generally received favorable reviews from participants. A list of development resources was placed on the AACP website.
Conclusions. This ongoing initiative is part of an AACP strategy to identify and address the professional development needs of department chairs. Survey results may also inform faculty members and other academic leaders about the roles and responsibilities of department chairs.
PMCID: PMC3425939  PMID: 22919099
department chair; leadership; administration; professional development; colleges of pharmacy
6.  Relationship between Vancomycin Trough Concentrations and Nephrotoxicity: a Prospective Multicenter Trial▿ 
Antimicrobial Agents and Chemotherapy  2011;55(12):5475-5479.
Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of >15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of >15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, gender, race, dose, length of therapy, use of other nephrotoxins (including contrast media), intensive care unit (ICU) residence, episodes of hypotension, and comorbidities. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a ≥50% increase from the baseline for two consecutive measurements. MICs of vancomycin for the MRSA isolates were also determined. A total of 288 patients were studied between February 2008 and June 2010, with approximately one-half having initial trough concentrations of ≥15 mg/ml. Nephrotoxicity was observed for 42 patients (29.6%) with trough concentrations >15 mg/ml and for 13 (8.9%) with trough concentrations of ≤15 mg/ml. Multivariate analysis revealed vancomycin trough concentrations of >15 mg/ml and race (black) as risk factors for nephrotoxicity in this population. Vancomycin trough concentrations of >15 mg/ml appear to be associated with a 3-fold increased risk of nephrotoxicity.
PMCID: PMC3232787  PMID: 21947388
8.  Benchmarking in Academic Pharmacy Departments 
Benchmarking in academic pharmacy, and recommendations for the potential uses of benchmarking in academic pharmacy departments are discussed in this paper. Benchmarking is the process by which practices, procedures, and performance metrics are compared to an established standard or best practice. Many businesses and industries use benchmarking to compare processes and outcomes, and ultimately plan for improvement. Institutions of higher learning have embraced benchmarking practices to facilitate measuring the quality of their educational and research programs. Benchmarking is used internally as well to justify the allocation of institutional resources or to mediate among competing demands for additional program staff or space. Surveying all chairs of academic pharmacy departments to explore benchmarking issues such as department size and composition, as well as faculty teaching, scholarly, and service productivity, could provide valuable information. To date, attempts to gather this data have had limited success. We believe this information is potentially important, urge that efforts to gather it should be continued, and offer suggestions to achieve full participation.
PMCID: PMC2987280  PMID: 21179251
benchmarking; pharmacy; academia
9.  Attributable Hospital Cost and Length of Stay Associated with Health Care-Associated Infections Caused by Antibiotic-Resistant Gram-Negative Bacteria▿  
Determination of the attributable hospital cost and length of stay (LOS) are of critical importance for patients, providers, and payers who must make rational and informed decisions about patient care and the allocation of resources. The objective of the present study was to determine the additional total hospital cost and LOS attributable to health care-associated infections (HAIs) caused by antibiotic-resistant, gram-negative (GN) pathogens. A single-center, retrospective, observational comparative cohort study was performed. The study involved 662 patients admitted from 2000 to 2008 who developed HAIs caused by one of following pathogens: Acinetobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., or Pseudomonas spp. The attributable total hospital cost and LOS for HAIs caused by antibiotic-resistant GN pathogens were determined by comparison with the hospital costs and LOS for a control group with HAIs due to antibiotic-susceptible GN pathogens. Statistical analyses were conducted by using univariate and multivariate analyses. Twenty-nine percent of the HAIs were caused by resistant GN pathogens, and almost 16% involved a multidrug-resistant GN pathogen. The additional total hospital cost and LOS attributable to antibiotic-resistant HAIs caused by GN pathogens were 29.3% (P < 0.0001; 95% confidence interval, 16.23 to 42.35) and 23.8% (P = 0.0003; 95% confidence interval, 11.01 to 36.56) higher than those attributable to HAIs caused by antibiotic-susceptible GN pathogens, respectively. Significant covariates in the multivariate analysis were age ≥12 years, pneumonia, intensive care unit stay, and neutropenia. HAIs caused by antibiotic-resistant GN pathogens were associated with significantly higher total hospital costs and increased LOSs compared to those caused by their susceptible counterparts. This information should be used to assess the potential cost-efficacy of interventions aimed at the prevention of such infections.
PMCID: PMC2798544  PMID: 19841152
10.  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.
PMCID: PMC1479119  PMID: 16723572
11.  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 μg/ml. Patients with inadequate clinical responses to linezolid may require more frequent dosing.
PMCID: PMC310170  PMID: 14693551
12.  Determination of Antibiotic Effect in an In Vitro Pharmacodynamic Model: Comparison with an Established Animal Model of Infection 
Antimicrobial Agents and Chemotherapy  2002;46(11):3574-3579.
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>4×MIC) and the change in the log10 CFU per milliliter (Δlog10 CFU/ml) in the central and peripheral compartments. Statistical analysis of the Δlog10 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 Δlog10 CFU/ml values were similar for the in vitro and animal models, but the y intercept was greater with the in vitro model. The Δlog10 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.
PMCID: PMC128701  PMID: 12384367
13.  Pharmacokinetics of Cefepime in Patients with Thermal Burn Injury 
Antimicrobial Agents and Chemotherapy  1999;43(12):2848-2854.
The pharmacokinetics of cefepime following administration of a single 2-g dose were evaluated for 12 adult patients with thermal burn injury and suspected or documented infection. Serial blood and urine samples for cefepime concentration determination were obtained for 24 h following drug administration. Serum and urine cefepime concentrations were determined by high-performance liquid chromatography and serum concentrations were fit to a two-compartment pharmacokinetic model. Mean (standard deviation [SD]) age, actual body weight (ABW), percent total body surface area burned, and days postburn at the time of study were 41 (13) years, 84 (22) kg, 36 (17)%, and 9 (3) days, respectively. Mean (SD) measured creatinine clearance (CLCR), total clearance (CLT), renal clearance (CLR), alpha phase half-life, beta phase half-life, and volume of distribution at steady state (VSS) were 135 (31) ml/min, 8.8 (2.4) liters/h, 8.1 (2.0) liters/h, 0.33 (0.14) h, 2.8 (0.6) h, and 0.43 (0.10) liters/kg ABW, respectively. Cefepime CLT and CLR in burn patients were similar to previously reported values for healthy volunteers when normalized by CLCR. Stepwise multiple regression was used to associate CLT with CLCR and days postburn (r2 = 0.861), CLR with CLCR and days postburn (r2 = 0.773), nonrenal clearance with percent third-degree (% 3°) burn and albumin concentration (r2 = 0.550), and VSS only with % 3° burn (r2 = 0.624). Simulated steady-state serum concentrations obtained by using the patients’ pharmacokinetic parameters exceeded the susceptibility interpretive standard (breakpoint) of cefepime for at least 60% of the dosing interval with dosing regimens of 1 g every 8 h (q8h), 2 g q8h, and 2 g q12h. Despite differences in pharmacokinetic parameters between our patients and healthy volunteers, it appears that these dosing regimens may be adequate in similar burn patients.
PMCID: PMC89575  PMID: 10582870
15.  Anti-Anaerobic Antimicrobial Agents: Cefoxitin, Cefotetan, Clindamycin, and Metronidazole 
Texas Heart Institute Journal  1990;17(2):77-85.
PMCID: PMC326456  PMID: 15227388
Antibiotics; bacteria, anaerobic; cefotetan; cefoxitin; clindamycin; metronidazole

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