Ben Lomaestro

Albany Stratton VA Medical Center, Albany, New York, United States

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Publications (57)217.83 Total impact

  • Joseph J. Carreno · Rachel M. Kenney · Ben Lomaestro
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    ABSTRACT: Vancomycin has been in clinical use for over 60 years, during which time renal toxicity has been well documented. Multiple risk factors and outcomes are associated with vancomycin-related nephrotoxicity. Risk factors include vancomycin exposure (trough levels 15 mg/L or higher, larger area under the curve, duration of therapy), host susceptibility to vancomycin (increased body weight, preexisting renal dysfunction, critical illness), and concurrent nephrotoxin therapy. Nephrotoxicity is associated with prolonged hospital stays, mortality, and the need for renal replacement therapy. To what degree vancomycin-associated nephrotoxicity exacerbates these adverse clinical outcomes remains unclear. This article reviews the current evidence on vancomycin-associated nephrotoxicity and explores future research directions with potential implications for improved patient safety.
    Pharmacotherapy 12/2014; 34(12). DOI:10.1002/phar.1488 · 2.20 Impact Factor
  • Sarah F Hale · Lauren Camaione · Ben M Lomaestro
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    ABSTRACT: To review the immunogenicity and safety of the Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (Hib-MenCY-TT) for infants and toddlers. Studies conducted in humans and limited to publication in English were identified through a MEDLINE (January 2000 to September 2013) search using the terms Hib-MenCY-TT, MenHibrix, and Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine. Clinical trial registries, Web sites, and reference citations from publications identified were reviewed for additional sources. Randomized controlled trials were included to evaluate the safety and immunogenicity of Hib-MenCY-TT. Epidemiological data and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. Hib-MenCY-TT is available for primary vaccination of infants as a 4-dose series at 2, 4, 6, and 12 to 15 months of age. Hib-MenCY-TT has comparable immunogenicity to licensed Hib vaccines and produces high levels of N meningitidis antibodies against serogroups C and Y. The most common adverse events were pain and redness at the injection site, drowsiness, and irritability. Hib-MenCY-TT has been demonstrated to be a safe and immunogenic vaccination for prevention of disease caused by N meningitidis serogroups C and Y and H influenzae type b in healthy infants and toddlers. Currently, the ACIP recommends the use of Hib-MenCY-TT specifically in high-risk infants aged 6 weeks to 18 months. Hib-MenCY-TT provides the first therapeutic option for vaccination of infants as young as 6 weeks of age who are at increased risk for meningococcal disease.
    Annals of Pharmacotherapy 12/2013; 48(3). DOI:10.1177/1060028013514375 · 2.92 Impact Factor
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    ABSTRACT: To compare the likelihood of alternative vancomycin dosing strategies based on weight, height, or body surface area (BSA) in achieving isometric vancomycin area under the serum concentration-time curve (AUC) values across the body size distribution of children and young adults. Maximum a posteriori probability Bayesian (MAP-Bayesian) pharmacokinetic analysis using retrospectively collected medical record data. Children's hospital. A total of 115 patients 1-20 years of age managed outside of the intensive care unit who were treated with vancomycin between May 1, 2011, and August 31, 2012, and had a minimum of two serum vancomycin concentration measurements. Vancomycin dosing and concentration-time information along with demographic and laboratory data related to kidney function estimation were extracted from the patients' medical records. A previously structured one-compartment model was used to derive MAP-Bayesian estimates of pharmacokinetic system parameters for each patient. Post hoc linear and power function regression were used to compare clearance (Cl) and the volume of distribution of the central compartment (Vc) to body size descriptors (weight, height, and BSA). The relationship of the body size descriptor-indexed parameter across the body size distribution was assessed. The AUC from time 0 to 24 hours (AUC24 ) values associated with vancomycin dosing regimens based on weight, height, and BSA were estimated. The 115 patients (56.5% male) had a mean ± SD age, height, and weight of 9.7 ± 5.4 years, 133 ± 32.3 cm, and 38.0 ± 24.2 kg, respectively. Each patient received a minimum of four doses of vancomycin and had two to nine serum vancomycin concentration measurements, for a total of 313 measurements for all patients. Vancomycin Cl was a nonlinear function of weight and a linear-proportionate function of BSA, whereas the volume of distribution of the central compartment (Vc) was a linear-proportionate function of weight. The expected median (5th-95th percentile) AUC24 values with weight-based dosing of vancomycin 60-70 mg/kg/day were 446 (315-834) mg·hour/L and 649 (385-1165) mg·hour/L in patients weighing less than 40 kg (n=72) and those weighing 40 kg or more (n=43), respectively. In contrast, isometric AUC24 values were predicted with BSA-based dosing across the body size distribution. BSA-based dosing is more likely than weight-based (mg/kg) dosing of vancomycin to achieve isometric AUC24 values across the body size distribution of children and young adults. Pharmacokinetic studies that compare these two vancomycin dosing strategies in children are clearly needed to validate these findings.
    Pharmacotherapy 12/2013; 33(12). DOI:10.1002/phar.1345 · 2.20 Impact Factor
  • Article: Vancomycin
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    ABSTRACT: Study Objective To compare the likelihood of alternative vancomycin dosing strategies based on weight, height, or body surface area (BSA) in achieving isometric vancomycin area under the serum concentration–time curve (AUC) values across the body size distribution of children and young adults. DesignMaximum a posteriori probability Bayesian (MAP‐Bayesian) pharmacokinetic analysis using retrospectively collected medical record data. SettingChildren's hospital. PatientsA total of 115 patients 1–20 years of age managed outside of the intensive care unit who were treated with vancomycin between May 1, 2011, and August 31, 2012, and had a minimum of two serum vancomycin concentration measurements. Measurements and Main ResultsVancomycin dosing and concentration‐time information along with demographic and laboratory data related to kidney function estimation were extracted from the patients' medical records. A previously structured one‐compartment model was used to derive MAP‐Bayesian estimates of pharmacokinetic system parameters for each patient. Post hoc linear and power function regression were used to compare clearance (Cl) and the volume of distribution of the central compartment (Vc) to body size descriptors (weight, height, and BSA). The relationship of the body size descriptor‐indexed parameter across the body size distribution was assessed. The AUC from time 0 to 24 hours (AUC24) values associated with vancomycin dosing regimens based on weight, height, and BSA were estimated. The 115 patients (56.5% male) had a mean ± SD age, height, and weight of 9.7 ± 5.4 years, 133 ± 32.3 cm, and 38.0 ± 24.2 kg, respectively. Each patient received a minimum of four doses of vancomycin and had two to nine serum vancomycin concentration measurements, for a total of 313 measurements for all patients. Vancomycin Cl was a nonlinear function of weight and a linear‐proportionate function of BSA, whereas the volume of distribution of the central compartment (Vc) was a linear‐proportionate function of weight. The expected median (5th–95th percentile) AUC24 values with weight‐based dosing of vancomycin 60–70 mg/kg/day were 446 (315–834) mg·hour/L and 649 (385–1165) mg·hour/L in patients weighing less than 40 kg (n=72) and those weighing 40 kg or more (n=43), respectively. In contrast, isometric AUC24 values were predicted with BSA‐based dosing across the body size distribution. ConclusionBSA‐based dosing is more likely than weight‐based (mg/kg) dosing of vancomycin to achieve isometric AUC24 values across the body size distribution of children and young adults. Pharmacokinetic studies that compare these two vancomycin dosing strategies in children are clearly needed to validate these findings.
    Pharmacotherapy 01/2013; 33(12). · 2.20 Impact Factor
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    ABSTRACT: While extended infusions of piperacillin-tazobactam (TZP) are increasingly used in practice, the effect of infusion on the pharmacokinetic (PK) profile of TZP has not been widely assessed. To assess its effect on the pharmacokinetic profile of TZP, seven serum samples were collected from 11 hospitalized patients who received 3.375 g TZP intravenously for 4 h every 8 h. Population pharmacokinetic models were fit to the PK data utilizing first-order, Michaelis-Menten (MM), and parallel first-order/MM clearance. A population PK model with first-order clearance was fit to the tazobactam PK data. Monte Carlo simulations (MCSs) were used to determine the most effective administration schedule to ensure that free piperacillin concentrations were above the MIC for at least 50% of the dosing interval (50% fT>MIC) and to quantify the extent of the nonlinear clearance. The model incorporating parallel linear/MM clearance best fit the piperacillin PK data. The MCSs demonstrated that approximately 50% of the administered piperacillin is cleared by the nonlinear clearance mechanism. The results of the MCSs also revealed that more intensive TZP extended infusion dosing schemes (3.375 to 4.5 g intravenously [3-h infusion] every 6 h) than those commonly used in clinical practice were needed to maximize the 50% fT>MIC for MICs of ≥8 mg/liter. This study suggests that extended infusion of TZP is the most effective method of administration for patients with nosocomial infections. Due to the hyperclearance nature of the hospitalized patient populations studied, more intensive TZP dosing regimens may be needed to maximize fT>MIC in certain hospitalized populations.
    Antimicrobial Agents and Chemotherapy 05/2012; 56(8):4087-94. DOI:10.1128/AAC.00521-12 · 4.45 Impact Factor
  • Ben M Lomaestro
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    ABSTRACT: Administration of vancomycin continues to be common despite perceived concerns of increased MICs, treatment failures and toxicity. In 2009, a consensus guideline was published in an effort to optimize dosing and monitoring of this useful agent. It was unique in targeting a specific antibiotic rather than a disease state or organism. However, a lack of prospective randomized double-blinded trials upon which to base guidelines was noted. In addition, several questions were raised and remain unanswered. Since guideline publication, new data has added to our understanding of the implications of aggressive dosing and subsequent monitoring. The following article discusses research published within the last 2 years.
    Expert Review of Anticancer Therapy 06/2011; 9(6):657-67. DOI:10.1586/eri.11.46 · 3.06 Impact Factor
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    ABSTRACT: We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L. At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%(.) At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered. This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin.
    Clinical Infectious Diseases 04/2011; 52(8):969-74. DOI:10.1093/cid/cir078 · 9.42 Impact Factor
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    Clinical Infectious Diseases 12/2009; 49(12):1965-1966. DOI:10.1086/648507 · 9.42 Impact Factor
  • Pharmacotherapy 11/2009; 29(11):1275-1279. DOI:10.1592/phco.29.11.1275 · 2.20 Impact Factor
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    ABSTRACT: Vancomycin is a commonly used antibiotic due to its effectiveness in treating serious gram-positive infections caused by methicillin-resistant Staphylococcus aureus. As commercial drug assays and a multitude of pharmacokinetic data from a variety of patient populations are widely available, therapeutic monitoring of serum vancomycin concentrations is frequently performed by clinicians, with the expectation that targeting the concentrations within a relatively narrow range can minimize toxicity yet still achieve therapeutic success. Much debate exists, however, over the value of routine therapeutic monitoring of vancomycin levels because of conflicting evidence regarding the ability of serum concentrations to predict effectiveness or prevent toxicity. In addition, studies have suggested that the potential for nephrotoxicity or ototoxicity with vancomycin monotherapy is minimal at conventional dosages of 1 g (15 mg/kg) every 12 hours. However, increased rates of nephrotoxicity have recently been reported with doses of 4 g/day or higher. The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists published a consensus statement on therapeutic monitoring of serum vancomycin levels in adults. These organizations established an expert panel to review the scientific data and controversies associated with vancomycin monitoring and to make recommendations based on the available evidence. As the members of this panel, we summarize the conclusions and highlight the recommendations from the consensus statement. We determined that the area under the concentration-time curve (AUC): minimum inhibitory concentration (MIC) ratio is the most useful pharmacodynamic parameter to predict vancomycin effectiveness and suggested a target ratio of 400 or greater to eradicate S. aureus. In addition, trough serum concentration monitoring is the most accurate and practical method to monitor vancomycin serum levels. Increasing trough concentrations to 15-20 mg/L to attain the target AUC:MIC ratio may be desirable but is currently not supported by clinical trials. Alternative therapies should be considered in patients with S. aureus infections that demonstrate a vancomycin MIC of 2 mg/L or greater because the target AUC:MIC ratio ( 400) is unlikely to be achieved in this setting. Increasing the dosage to result in higher trough concentrations may increase the potential for toxicity; however additional clinical experience is required to determine the extent.
    Pharmacotherapy 11/2009; 29(11):1275-9. · 2.20 Impact Factor
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    ABSTRACT: Data suggest that higher doses of vancomycin can increase the risk of nephrotoxicity. No study has been undertaken to determine the pharmacodynamic index (ie, the area under the curve [AUC] or the trough value) that best describes the relationship between vancomycin exposure and onset of nephrotoxicity. A retrospective study was conducted among patients who received vancomycin for a suspected or proven gram-positive infection during the period from 1 January 2005 through 31 December 2006 at Albany Medical Center Hospital. Patients were included in our study if they (1) were > or =18 years old, (2) had an absolute neutrophil count of > or =1000 cells/mm(3), (3) received vancomycin for >48 h, (4) had 1 vancomycin trough level collected within 96 h of vancomycin therapy, and (5) had a baseline serum creatinine level of <2.0 mg/dL. Patients were excluded if they (1) had a diagnosis of cystic fibrosis, (2) received intravenous contrast dye within 7 days of starting vancomycin or during therapy, or (3) required vasopressor support during therapy. Demographics, comorbid conditions, and treatment data were collected. The highest observed vancomycin trough value within 96 h of initiation of vancomycin therapy and the estimated vancomycin AUC were analyzed as measures of vancomycin exposure. The vancomycin AUC value from 0 to 24 h at steady state (in units of mg x h/L) for each patient was estimated by use of the maximum a posteriori probability Bayesian procedure in ADAPT II. Nephrotoxicity was defined as an increase in serum creatinine level of 0.5 mg/dL or 50%, whichever was greater, following initiation of vancomycin therapy. Logistic and Cox proportional hazards regression models identified the vancomycin pharmacodynamic index that best describes the relationship between vancomycin exposure and toxicity. During the study period, 166 patients met the inclusion criteria. Both initial vancomycin trough values and 0-24-h at steady state AUC values were associated with nephrotoxicity in the bivariate analyses. However, the vancomycin trough value, modeled as a continuous variable, was the only vancomycin exposure variable associated with nephrotoxicity in the multivariate analyses. The results indicate that a vancomycin exposure-toxicity response relationship exists. The vancomycin trough value is the pharmacodynamic index that best describes this association.
    Clinical Infectious Diseases 09/2009; 49(4):507-14. DOI:10.1086/600884 · 9.42 Impact Factor
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    ABSTRACT: Practice guidelines for therapeutic monitoring of vancomycin treatment for Staphylococcus aureus infection in adult patients were reviewed by an expert panel of the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. A literature review of existing evidence regarding vancomycin dosing and monitoring of serum concentrations, in addition to patient outcomes combined with expert opinion regarding the drug's pharmacokinetic, pharmacodynamic, and safety record, resulted in new recommendations for targeting and adjustment of vancomycin therapy.
    Clinical Infectious Diseases 08/2009; 49(3):325-7. DOI:10.1086/600877 · 9.42 Impact Factor
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    ABSTRACT: Vancomycin is a glycopeptide antibiotic that has been in clinical use for nearly 50 years as a penicillin alternative to treat penicillinaseproducing strains of Staphylococcus aureus. It is one of the most widely used antibiotics in the United States for the treatment of serious gram-positive infections involving methicillin-resistant S. aureus (MRSA). 1 Early use of vancomycin was associated with a number of adverse effects, including infusionrelated toxicities, nephrotoxicity, and possible ototoxicity. Upon further
    American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 02/2009; 66(1):82-98. DOI:10.2146/ajhp080434 · 2.21 Impact Factor
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    ABSTRACT: There is growing concern that vancomycin has diminished activity for methicillin-resistant Staphylococcus aureus (MRSA) infections, with vancomycin MICs at the high end of the CLSI susceptibility range. Despite this growing concern, there are limited clinical data to support this notion. To better elucidate this, a retrospective cohort study was conducted among patients with MRSA bloodstream infections who were treated with vancomycin between January 2005 and May 2007. The inclusion criteria were as follows: at least 18 years old, nonneutropenic, with an MRSA culture that met the CDC criteria for bloodstream infection, had received vancomycin therapy within 48 h of the index blood culture, and survived >24 h after vancomycin administration. Failure was defined as 30-day mortality, bacteremia >or=10 days on vancomycin therapy, or a recurrence of MRSA bacteremia within 60 days of vancomycin discontinuation. Classification and regression tree (CART) analysis identified the vancomycin MIC breakpoint associated with an increased probability of failure. During the study period, 92 patients met the inclusion criteria. The vancomycin MIC breakpoint derived by CART analysis was >or=1.5 mg/liter. The 66 patients with vancomycin MICs of >or=1.5 mg/liter had a 2.4-fold increase in failure compared to patients with MICs of <or=1.0 mg/liter (36.4% and 15.4%, respectively; P = 0.049). In the Poisson regression, a vancomycin MIC of >or=1.5 mg/liter was independently associated with failure (adjusted risk ratio, 2.6; 95% confidence interval, 1.3 to 5.4; P = 0.01). These data strongly suggest that patients with MRSA bloodstream infections with vancomycin MICs of >or=1.5 mg/liter respond poorly to vancomycin. Alternative anti-MRSA therapies should be considered for these patients.
    Antimicrobial Agents and Chemotherapy 06/2008; 52(9):3315-20. DOI:10.1128/AAC.00113-08 · 4.45 Impact Factor
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    Thomas P Lodise · Ben Lomaestro · Jeffrey Graves · G L Drusano
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    ABSTRACT: Recent guidelines recommend vancomycin trough concentrations between 15 and 20 mg/liter. In response, some clinicians increased vancomycin dosing to >or=4 g/day. Scant data are available regarding toxicities associated with higher vancomycin doses. The purpose of this study was to examine vancomycin-associated nephrotoxicity at >or=4 g/day. To accomplish the study objective, a cohort study among a random selection of patients receiving vancomycin or linezolid between 2005 and 2006 was performed. Patients were included if they (i) were >or=18 years of age, (ii) were nonneutropenic, (iii) were on therapy for >48 h, (iv) had baseline serum creatinine levels of <2.0 mg/dl, (v) did not suffer from cystic fibrosis, and (vi) had no intravenous contrast dye within the previous 7 days. For drug exposure, three treatment strata were created: standard vancomycin dose (<4 g/day), high vancomycin dose (>or=4 g/day), and linezolid. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/dl or 50%, whichever was greater, after therapy initiation. Stratified Kaplan-Meier analysis and Cox modeling were used to compare times to nephrotoxicity across groups. During the study, 246 patients on vancomycin (26 patients taking >or=4 g/day and 220 patients taking <4 g/day) and 45 patients on linezolid met the criteria. A significant difference in nephrotoxicity between patients receiving >or=4 g vancomycin/day, those receiving <4 g vancomycin/day, and those receiving linezolid was noted (34.6%, 10.9%, and 6.7%, respectively; P = 0.001), and Kaplan-Meier analysis identified significant differences in time to nephrotoxicity for the high-vancomycin-dose cohort compared to those for groups taking the standard dose and linezolid. In the Cox model, patients taking >or=4 g vancomycin/day, a total body weight of >or=101.4 kg, estimated creatinine clearance of </=86.6 ml/min, and intensive care unit residence were independently associated with time to nephrotoxicity. The data suggest that higher-dose vancomycin regimens are associated with a higher likelihood of vancomycin-related nephrotoxicity.
    Antimicrobial Agents and Chemotherapy 05/2008; 52(4):1330-6. DOI:10.1128/AAC.01602-07 · 4.45 Impact Factor
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    ABSTRACT: 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. Retrospective cohort study. Integrated Veterans Administration (VA) health care system. Nine hundred thirty-seven elderly (>or= 65 yrs) patients with documented blood glucose levels of 65-140 mg/dl before receiving a fluoroquinolone. 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. Higher rates of both hypoglycemia and hyperglycemia were noted among elderly hospitalized patients who received gatifloxacin compared with those receiving levofloxacin, irrespective of dosing.
    Pharmacotherapy 11/2007; 27(11):1498-505. DOI:10.1592/phco.27.11.1498 · 2.20 Impact Factor
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    ABSTRACT: Although a growing number of studies have found a relationship between delayed appropriate antibiotic therapy and mortality, few have attempted to quantify the temporal association between delayed appropriate antibiotic therapy and mortality. This study was designed to measure the elapsed time associated with an increased risk of 30-day mortality among patients with Pseudomonas aeruginosa bacteremia. The retrospective cohort study was conducted among immunocompetent, adult patients with P. aeruginosa bacteremia onset at least 2 days after hospital admission between 1 January 2001 and 30 September 2006. Classification and regression tree analysis (CART) was used to identify the delay in appropriate antibiotic therapy that was associated with an increased risk of 30-day mortality. During the study period, 100 patients met the inclusion criteria. The CART-derived breakpoint between early and delayed treatment was 52 h. The delayed treatment group experienced a >2-fold significant increase in 30-day mortality compared to the early treatment group (44 and 19%, respectively, P = 0.008). Delayed appropriate therapy of >52 h (odds ratio [OR] = 4.1; 95% confidence interval [CI] 1.2 to 13.9, P = 0.03) was independently associated with 30-day mortality in the multivariate analysis. Antibiotic resistance > or =3 classes (adjusted OR [AOR] = 4.6; 95% CI = 1.9 to 11.2, P = 0.001) and chronic obstructive pulmonary disease (AOR = 5.4; 95% CI = 1.5 to 19.7, P = 0.01) were independently associated with delayed appropriate therapy of >52 h. The data strongly suggest that delaying appropriate therapy for approximately 2 days significantly increases the risk of 30-day mortality in patients with P. aeruginosa bloodstream infections.
    Antimicrobial Agents and Chemotherapy 11/2007; 51(10):3510-5. DOI:10.1128/AAC.00338-07 · 4.45 Impact Factor
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    ABSTRACT: Background: Recent HCAP guidelines recommend considerably higher V target troughs (15-20 mg/L). The incidence of N associated with the higher V doses used to achieve this new target is largely unknown. Objective: To examine the relationship between V dosing and incidence of N in hospitalized patients. We also included linezolid (L), a drug known to not cause N, in the analysis to serve as a non-V control group and as a measure of the non-V N in the study population. Methods: Study period: 1/05-1/06. Inclusion criteria: (1) ≥ 18 yrs, (2) non-neutropenic, (3) received V or L for > 48 h, (4) baseline serum creatinine <2 mg/dL, (5) non-cystic fibrosis pts, and (6) did not received IV contrast dye within 7 d. Demographics, co-morbid conditions, microbiology, and treatment data were collected. V AUCss (mg*hour/L) was calculated from a V demographics model. CART was used to identify the range of V AUCs associated with an increased probability of N. N was defined as an increase in serum creatinine of 0.5mg/dl or 50%, whichever was greater, 48 h after the initiation of V or L. Results: During the study period, 246 randomly selected V patients and 45 randomly selected L patients met criteria. Age was different between groups. No other baseline differences were seen across groups. Stratified Cox modeling demonstrated that V AUC had a significant impact on N (P=0.002). Weight and ICU residence also had a significant impact on N. Conclusions: A significant relationship between V AUC and N was observed. Larger V doses that have a higher likelihood of attaining target troughs are associated with V exposures (AUC) that have a higher probability of V-related N.
    Infectious Diseases Society of America 2007 Annual Meeting; 10/2007
  • Andrea Kwa · Ben Lomaestro · George Drusano · Thomas Lodise
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    ABSTRACT: Background: Based on a Monte Carlo Simulation (MCS) that used healthy subject PK data, EI-PIP (3.375 G infused (inf) over 4 hours Q8H) was adopted as the preferred PIP dosing regimen at our institution. It has been shown that healthy subject PK data often provides a biased estimate of the probability of target attainment (PTA). The purpose of this study was to describe the PD profile of EI-PIP using PK data from hospitalized patients (pts) that received EI-PIP. Methods: Plasma PIP samples were collected in 13 pts receiving EI-PIP. Plasma concentration-time profiles were modeled using a 2-com model with zero-order inf & 1st order elimination & transfer. Model parameters were identified in a population PK analysis (NPAG). A MCS (ADAPT II) of 9999 subjects was performed to estimate the PTA of f50% T>MIC for PIP 3.375 G IV Q8H (4 hr inf), PIP 3.375 G IV Q6H (0.5 hr inf) & PIP 4.5 G IV Q6H (0.5 hr inf). The P. aeruginosa isolates from the SENTRY North America Bloodstream Infections Program (2003-05) were used as the distribution of MICs for the P. aeruginosa 50% fT>MIC PTA analysis. Results: After the Bayesian step, the overall fit of the model to the data was good and plots of predicted vs. observed plasma concentrations showed a slope and intercept very close to the ideal values of 1.0 and 0.0, respectively In the P. aeruginosa 50% fT>MIC PTA analysis, the PTA for PIP 3.375 G IV Q8H (4-hr inf) was 80.4%. For PIP 3.375 G IV Q6H (0.5 hr inf) & PIP 4.5 G IV Q6H (0.5 hr inf), the PTA was 62.8% and 66.5%, respectively. Conclusions: Using EI-PIP PK data for hospitalized pts, EI-PIP was found to have a superior PD profile when compared to standard PIP intermittent inf regimens.
    Infectious Diseases Society of America 2007 Annual Meeting; 10/2007
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    Thomas Lodise · Ben Lomaestro · George Drusano
    Clinical Infectious Diseases 07/2007; 45(2):269-270. DOI:10.1086/518979 · 9.42 Impact Factor

Publication Stats

3k Citations
217.83 Total Impact Points

Institutions

  • 1994–2013
    • Albany Stratton VA Medical Center
      Albany, New York, United States
  • 2012
    • Singapore General Hospital
      • Department of Pharmacy
      Tumasik, Singapore
  • 1992–2011
    • Albany Medical College
      • • Division of Clinical Pharmacology
      • • Department of Medicine
      Albany, New York, United States
  • 2009
    • Wayne State University
      Detroit, Michigan, United States
  • 2007
    • Albany College of Pharmacy and Health Sciences
      • Department of Pharmacy Practice
      Albany, New York, United States
    • Oregon State University
      • College of Pharmacy
      Corvallis, Oregon, United States