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Manjunath P Pai

Publications and source records attributed to Manjunath P Pai.

At least 19 recordsLinked to original sources
PubMed2006

Association of fluconazole area under the concentration-time curve/MIC and dose/MIC ratios with mortality in nonneutropenic patients with candidemia.

The present study tested in vitro susceptibility of Candida bloodstream isolates to fluconazole to determine if the ratio of the fluconazole area under the concentration-time curve (AUC) or weight-normalized daily dose (dose(wn)) to MIC correlated with mortality. Fluconazole susceptibility and outcome data were determined for 77 patients with a positive Candida blood culture between 2002 and 2005. The most commonly isolated Candida species were C. albicans (64%), C. glabrata (14%), C. parapsilosis (8%), C. tropicalis (6%), and C. lusitaniae (4%). Only two isolates were classified as fluconazole resistant by the CLSI M27-A2 method. Fluconazole MICs were highest against C. glabrata relative to other Candida species. Overall the crude mortality assessed at hospital discharge was 19.4% (n = 15). Mortality rates by species were as follows: C. albicans, 16.3%; C. glabrata, 36.4%; C. parapsilosis, 0%; C. tropicalis, 0%; C. lusitaniae, 33.3%. A mortality rate of 50% was noted among patients infected with nonsusceptible isolates (MIC > or = 16 microg/ml) compared to 18% for patients infected with susceptible (MIC < or = 8 microg/ml) isolates (P = 0.17). The fluconazole dose(wn)/MIC (24-h) values were significantly higher for the 62 survivors (13.3 +/- 10.5 [mean +/- standard deviation]) compared to the 15 nonsurvivors (7.0 +/- 8.0) (P = 0.03). The fluconazole AUC/MIC (24 h) values also trended higher for survivors (775 +/- 739) compared to nonsurvivors (589 +/- 715) (P = 0.09). These data support the dose-dependent properties of fluconazole. Underdosing fluconazole against less-susceptible Candida isolates has the potential to increase the risk of mortality associated with candidemia.

Adult↗
PubMed2006

Non-transferrin-bound iron is associated with enhanced Staphylococcus aureus growth in hemodialysis patients receiving intravenous iron sucrose.

BACKGROUND: Hemodialysis vascular access infections are most frequently caused by Staphylococcus spp. The purpose of this study was to determine if S. aureus growth is enhanced after administration of IV iron sucrose and to establish a relationship between the appearance of non-transferrin-bound iron (NTBI) and S. aureus growth. METHODS: Serum samples were obtained from 12 hemodialysis patients receiving maintenance doses of 100 mg of iron sucrose at baseline and 5, 30, 90, 220 min and 48 h after iron administration. Assays for NTBI and transferrin saturation were performed. S. aureus isolates were used to inoculate patient serum samples. Bacterial growth was determined by optical density. RESULTS: Six of 12 patients had NTBI present within 30 min of the iron dose. NTBI was present more frequently in patients with baseline transferrin saturation values >30% (p < 0.05). Bacterial growth was significantly greater in patients who had NTBI present at 5, 90 and 220 min after iron administration compared to those who did not have NTBI present. CONCLUSIONS: Doses of 100 mg of iron sucrose are associated with the presence of NTBI and enhanced S. aureus growth.

Female↗
PubMed2006

Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study.

BACKGROUND: Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality. METHODS: We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast. RESULTS: A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05). CONCLUSION: A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, are needed.

Adult↗
PubMed2006

Using vancomycin concentrations for dosing daptomycin in a morbidly obese patient with renal insufficiency.

OBJECTIVE: To report a case in which vancomycin clearance was used to determine the daptomycin dosing interval in a morbidly obese patient with renal impairment. CASE SUMMARY: A 46-year-old man (209 kg; 178 cm) failed a 42 day course of vancomycin therapy for treatment of a methicillin-resistant Staphylococcus aureus-infected wound and cellulitis. The median trough vancomycin concentration was 12.6 microg/mL (range 7.3-24.1) through his course of therapy. Estimation of creatinine clearance (Cl(cr)) was confounded in this clinical scenario, given the patient's weight and a lack of valid equations in this patient population. Daptomycin was administered empirically at 6 mg/kg dosed every 48 hours based on estimated clearance from measured vancomycin concentrations. Steady-state plasma concentrations of daptomycin were determined, and the daptomycin half-life in this patient was more accurately estimated using vancomycin clearance as a surrogate. In addition, a 4 mg/kg dose of daptomycin would have been sufficient based on plasma concentrations. The patient demonstrated rapid clinical improvement and remained free of cellulitis for 6 months after completion of daptomycin and a 12 week course of trimethoprim/sulfamethoxazole. DISCUSSION: The dosing interval of daptomycin is adjusted based on Cl(cr). However, estimation of Cl(cr) is difficult in morbidly obese patients with renal impairment, given a lack of valid equations. In this clinical scenario, vancomycin concentrations were used to estimate Cl(cr) and served as a surrogate measure to determine the daptomycin dosing interval. Measured daptomycin concentrations validated this approach and confirmed the inadequacy of commonly used Cl(cr) equations. CONCLUSIONS: In this clinical scenario, vancomycin concentrations more accurately estimated Cl(cr), thereby facilitating determination of the daptomycin dosing interval.

Anti-Bacterial Agents↗
PubMed2006

Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

BACKGROUND: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. METHODS: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. RESULTS: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. CONCLUSIONS: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.

Adolescent↗
PubMed2006

Epidemiology of vancomycin-induced neutropenia in patients receiving home intravenous infusion therapy.

BACKGROUND: Vancomycin is frequently used to manage serious resistant gram-positive infections. Neutropenia, whose epidemiology has not been well characterized, is a potentially serious adverse event associated with the use of vancomycin. OBJECTIVE: To characterize the incidence and risk factors for development of vancomycin-induced neutropenia in patients treated with home intravenous vancomycin therapy. METHODS: A retrospective chart review was conducted of adult patients receiving vancomycin therapy through the University of New Mexico Home Intravenous Infusion Clinic between January 1998 and December 2004. Data collection included demographics, comorbid conditions, dose and duration of vancomycin therapy, indications for vancomycin use, vancomycin concentrations, all concurrent medications, laboratory data, culture and susceptibility data, reasons for antibiotic alteration or discontinuations, all other recorded adverse events, management of adverse events, and outcomes of adverse events. RESULTS: A total of 372 charts of patients managed through the clinic were reviewed and 114 patients treated with vancomycin were identified. Fourteen (12%) cases of vancomycin-induced neutropenia were identified; 4 (3.5%) cases included a reduction in absolute neutrophil count to 500 cells/mm3 or less. The mean +/- SD duration of vancomycin therapy and time to neutropenia were 32 +/- 29 and 26 +/- 15 days, respectively. Laboratory monitoring was performed on a weekly basis and resolution of vancomycin-induced neutropenia occurred promptly after discontinuation. Total vancomycin doses used and serum concentrations were not associated with the development of neutropenia. CONCLUSIONS: Vancomycin-induced neutropenia may occur at a higher frequency than previously reported. Clinicians should monitor hematologic parameters at least weekly in patients receiving home intravenous vancomycin therapy.

Adult↗
PubMed2006

Antibiotic drug interactions.

Drug-drug interactions in the field of infectious diseases continue to expand as new drugs are approved, metabolic enzymes and transporters are identified, and recommendations for co-administration of drugs are revised. This article provides an overview of the principles and mechanisms of drug-drug interactions and describes pharmacokinetic-pharmacodynamic interactions commonly associated with antibacterial therapy, antiviral agents (non-retroviral), and drugs for tuberculosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Optimizing antimicrobial therapy for gram-positive bloodstream infections in patients on hemodialysis.

Infections with gram-positive organisms are highly prevalent in hemodialysis patients and are a major cause of morbidity and mortality in this population. Antimicrobial therapy is widely used to treat these infections, and prolonged therapy with these agents is often necessary. Extensive use of antimicrobials in hemodialysis patients has resulted in a growing threat of resistance, especially among gram-positive bacteria such as Enterococcus spp and Staphylococcus aureus. Vancomycin-resistant enterococci and S. aureus isolates with reduced susceptibility to vancomycin are increasingly being reported in hemodialysis patients. Additionally, resistance of these organisms to newer agents, such as linezolid and daptomycin, has been documented. Appropriate utilization of antimicrobial therapy to treat these organisms requires an understanding of the pharmacokinetic and pharmacodynamic principles to optimize therapy and avoid adverse drug events. The pharmacokinetic and pharmacodynamic profile of antimicrobial agents can be significantly altered in patients with chronic kidney disease. This review will describe mechanisms of antimicrobial resistance among common gram-positive organisms. The pharmacokinetic and pharmacodynamic principles of cephalosporins, vancomycin, aminoglycosides, linezolid, and daptomycin and applications for use of these agents in the treatment of patients with bloodstream infections on hemodialysis are discussed.

Anti-Bacterial Agents↗
PubMed2005

Assessment of effective renal plasma flow, enzymuria, and cytokine release in healthy volunteers receiving a single dose of amphotericin B desoxycholate.

The present study assessed potential subclinical markers of amphotericin B (AmB)-related nephrotoxicity and infusion-related reactions (IRR). Subjects were pretreated with diphenhydramine and acetaminophen and received a 500-ml bolus infusion of 0.9% sodium chloride prior to each effective renal plasma flow (ERPF) assessment. ERPF was measured before and after administration of a single 0.25-mg/kg intravenous AmB dose using technetium-99m mercaptoacetyltriglycine. Blood was collected before and 3 h after AmB infusion for tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) plasma concentrations. Overnight 12-h urine collections were performed before administration of AmB and for 2 nights after administration of AmB and analyzed for alpha and pi glutathione-S-transferases (GSTalpha and GSTpi, respectively) and N-acetyl-beta-d-glucosaminidase (NAG). Six men and six women with mean +/- standard deviation (SD) ages of 24.8 +/- 5.3 and 28.0 +/- 8.5 years, respectively, were studied. Baseline serum creatinine values were within the normal range and were unaltered after administration of AmB. The mean +/- SD decrease in ERPF after administration of AmB was significant (P < 0.05) in males (15.7 +/- 8.1%) but not females (9.5 +/- 14.0%). The GSTpi and GSTalpha indices increased significantly (P < 0.05) by two to fourfold and returned to baseline in males but were unaltered in females. NAG indices were unaffected by AmB. Six patients experienced an IRR that was associated with increased TNF-alpha (P < 0.05) but not IL-1beta (P = 0.09). These results suggest a potential sex-related difference in AmB-induced nephrotoxicity and provide a rationale for use of ERPF, urine GST, and TNF-alpha as subclinical markers of polyene-induced toxicity.

Adolescent↗
PubMed2004

Treatment of a chronic Scedosporium apiospermum vertebral osteomyelitis. Case report.

Scedosporium apiospermum is a rare cause of fungal vertebral osteomyelitis that may result in chronic infection requiring multiple surgical interventions and long-term medical therapy. This case is the seventh one reported in the literature and is the first to include salvage surgery of a previous major spinal reconstruction. This report is also the first to describe the use of the new antifungal agent voriconazole. In treating this case of chronic vertebral osteomyelitis, several principles are emphasized from both the surgical and medical perspectives. From a surgical perspective, the use of salvage surgery, temporary avoidance of spinal instrumentation, and an appropriate choice of graft materials are emphasized. From a medical perspective, confirmation of the diagnosis, the need for long-term antifungal therapy, the need for long-term patient compliance, and the use of the new antifungal agent voriconazole are emphasized. Application of these principles has led to an adequate 2-year outcome.

Adult↗
PubMed2004

Adjunctive granulocyte colony-stimulating factor therapy for diabetic foot infections.

OBJECTIVE: To evaluate the role of granulocyte colony-stimulating factor (G-CSF) as adjunctive therapy for the treatment of diabetic foot infections in non-neutropenic patients. DATA SOURCES: Clinical literature was accessed through MEDLINE (1965-April 2004). Key search terms included G-CSF, infection, and diabetes. In addition, relevant references from primary and secondary article bibliographies were extracted. DATA SYNTHESIS: Three clinical trials evaluating G-CSF for diabetic foot infections were identified. These data demonstrated positive effects of G-CSF on improvement of foot infections and risk of amputations. CONCLUSIONS: Controlled trials are necessary to validate the role of adjunctive G-CSF at reducing amputations in patients with diabetic foot infections.

Anti-Infective Agents↗
PubMed2004

Vancomycin dosing in high flux hemodialysis: a limited-sampling algorithm.

PURPOSE: The feasibility of using a limited-sampling algorithm for administration of vancomycin for treatment of vascular-access-related bacteremia in outpatient high flux hemodialysis was investigated. METHODS: The original vancomycin-dosing algorithm used at our hemodialysis unit required stat orders for serum vancomycin concentrations before each hemodialysis session to determine the dose of vancomycin to be administered posthemodialysis. Vancomycin concentration data obtained using this original algorithm from January through September 2001 were retrospectively analyzed to determine how many vancomycin concentrations measured 5-20 microg/mL and identify potential clinical predictors of vancomycin removal. RESULTS: A total of 409 serum vancomycin concentrations were drawn during the study period. Ninety-seven percent of concentrations drawn were within 5-20 microg/mL. Twenty-eight patients had data evaluable to determine pharmacokinetic parameters. Mean +/- S.D. vancomycin removal was 39% +/- 13%. Body weight and duration of dialysis alone, blood flow rate, and dialysate flow rate were not predictive of vancomycin removal. Based on these data, a revised algorithm with limited vancomycin sampling data was initiated in December 2002. Retrospective analysis of concentrations obtained and achieved by this algorithm demonstrated a 70% reduction in the number of vancomycin concentration determinations, with 93% of these concentrations within 5-20 microg/mL. The estimated annual cost saving to the hemodialysis unit with the revised algorithm was 7552 dollars. CONCLUSION: A vancomycin-dosing algorithm using limited concentration monitoring for hemodialysis patients achieved comparable vancomycin concentrations to those found with more frequent monitoring and resulted in significant cost savings.

Algorithms↗
PubMed2004

Extended-interval aminoglycoside dosing for treatment of enterococcal and staphylococcal osteomyelitis.

BACKGROUND: Gram-positive osteomyelitis requires long-term antibiotic therapy, much of which is often administered in the outpatient setting. Historically, synergistic aminoglycoside use in these infections requires multiple daily doses, which can be inconvenient. Data regarding extended-interval aminoglycoside dosing (EIAD), also known as once-daily dosing, in this setting are lacking. OBJECTIVE: To evaluate the safety and efficacy of EIAD in the treatment of gram-positive osteomyelitis. METHODS: Retrospective chart review of adult patients treated for documented, gram-positive osteomyelitis with EIAD at the University of New Mexico Home IV Antibiotic Clinic was conducted. The patients' medical records were reviewed by an infectious diseases clinical pharmacist. Clinical and microbiologic outcomes and the incidence of nephrotoxicity and ototoxicity were the main outcome measures. RESULTS: Fifteen patients (16 events) were included. Enterococcus spp. was the most common organism isolated. Nine patients had infected equipment or devices; 6 of these had removal of these devices in conjunction with antibiotic therapy. The median duration of antibiotic therapy was 6 weeks (range 6-31). The median duration of aminoglycoside therapy was 28 days (range 6-43). Seven patients developed nephrotoxicity, 5 of whom received an aminoglycoside in combination with vancomycin. Male patients had a higher risk of developing nephrotoxicity compared with females (p = 0.04). The mean +/- SD duration of EIAD before the development of nephrotoxicity was 34 +/- 8 days. Clinical cure was achieved in 12 (75%) patients. Three patients achieved clinical cure without hardware removal. CONCLUSIONS: Most of the patients with gram-positive osteomyelitis were successfully managed with EIAD. However, nephrotoxicity developed in a high proportion of patients and was likely related to prolonged aminoglycoside use.

Adult↗
PubMed2004

Altered susceptibility of Candida glabrata bloodstream isolates to triazoles at clinically relevant pH values: comparison of the NCCLS M27-A2, Sensititre YeastOne, and Etest methods.

We studied the MICs of triazoles against 15 Candida glabrata clinical isolates by the NCCLS M27-A2, Sensititre YeastOne, and Etest methods by using media at pHs 6.0, 7.0, and 7.4. Thirteen isolates were less susceptible to triazoles at pH 6.0 and more susceptible to triazoles at pH 7.4 compared to pH 7.0.

Antifungal Agents↗
PubMed2004

Sex-related differences in the pharmacokinetics of once-daily saquinavir soft-gelatin capsules boosted with low-dose ritonavir in patients infected with human immunodeficiency virus type 1.

STUDY OBJECTIVES: To compare the steady-state pharmacokinetics and safety of saquinavir soft-gelatin capsules (SGC) plus low-dose ritonavir administered once/day in antiretroviral-naive adult patients infected with the human immunodeficiency virus type 1 (HIV-1) and to evaluate any sex-related differences. DESIGN: Single-center, open-label, pharmacokinetic study. SETTING: University-affiliated outpatient HIV clinic. PATIENTS: Six men and seven women with HIV-1. INTERVENTION: Each patient received saquinavir SGC 1600 mg and ritonavir 100 mg for a 14-day course of therapy. Nine serial blood samples during 24 hours were collected on day 14 of therapy MEASUREMENTS AND MAIN RESULTS: Plasma saquinavir and ritonavir concentrations were measured by high-performance liquid chromatography. Standard noncompartmental methods were used to calculate the pharmacokinetic parameters. The unpaired Student t test was used for the statistical comparison of pharmacokinetic parameters between male and female patients. Once-daily saquinavir SGC plus ritonavir was generally well tolerated. Pharmacokinetic data from five men and five women were evaluable. The median saquinavir area under the concentration-time curve from 0-24 hours (AUC0-24) in the female patients (82,300 ng x hr/ml) was significantly (p=0.036) higher than that in the male patients (47,400 ng x hr/ml). This relationship remained significant for weight-adjusted saquinavir AUC0-24 values. Ritonavir's apparent oral clearance in the women was significantly (p=0.023) lower than that in the men. CONCLUSION: Significantly higher plasma concentrations of saquinavir were achieved in female compared with male HIV-infected patients receiving once-daily saquinavir SGC 1600 mg plus ritonavir 100 mg.

Adult↗
PubMed2003

Antifungal susceptibility testing in teaching hospitals.

BACKGROUND: An assessment of antifungal susceptibility testing (AST) has not been conducted since the introduction of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A document. OBJECTIVE: To determine AST practices in teaching hospitals. METHODS: A questionnaire was mailed to the heads of 386 randomly assigned microbiology departments from teaching hospitals identified through the 2000 American Hospital Association Guide. Identifiers were used to delineate responders from nonresponders. A reminder letter was mailed 3 weeks after the initial mailing to all nonresponders. The hospital bed-size and number of inpatient days for respondents were obtained through the American Hospital Directory. RESULTS: The questionnaire was returned by 171 (44.3%) institutions. The total and median (range) number of candida isolates were 137,088 and 8.5 (1-145)/1000 inpatient days for the year 2000, respectively. Approximately 1% (1300) of candida isolates, from predominantly blood specimens, underwent AST. AST was reported by 115 (67.2%) hospitals, with testing on site at 27 hospitals and off site for 88 hospitals. NCCLS methodology (80% broth microdilution) was used by 75% of the hospitals performing on-site AST. The median time to obtain AST results was significantly lower when testing was performed on site (3 d) compared with off site (7-10 d). SUMMARY: A large number of candida bloodstream isolates undergoes AST annually. AST results are obtained sooner when performed on site compared with off site.

Candida↗