The relationship of vancomycin 24-hour AUC and trough concentration.

PURPOSE: Prior to the 2020 release of a joint consensus guideline on monitoring of vancomycin therapy for serious methicillin-resistant Staphylococcus aureus (MRSA) infections, clinicians had escalated vancomycin doses for 2 decades while targeting trough concentrations of 15 to 20 µg/mL, leading to an increased frequency of nephrotoxicity. For MRSA infections, the 2020 guideline recommends adjusting doses to achieve a 24-hour area under the concentration-time curve (AUC) of 400 to 600 µg · h/mL; however, monitoring of trough concentrations has been entrenched for 3 decades. Calculating dose regimens based on AUC will require obtaining an increased number of vancomycin serum concentrations and, possibly, advanced software. The aim of this investigation was to determine the relationship between AUC and trough concentration and the influence of dosing regimen on goal achievement. METHODS: The relationship between trough concentration and AUC was explored through derivation of an equation based on a 1-compartment model and simulations. RESULTS: 24-hour AUC is related to dosing interval divided by half-life in a nonlinear fashion. The target trough concentration can be individualized to achieve a desired AUC range, and limiting use of large doses (>15-20 mg/kg) can protect against excessive 24-hour AUC with trough-only monitoring. CONCLUSION: After initially determining pharmacokinetic parameters, subsequent monitoring of AUC can be accomplished using trough concentrations only. Trough concentration may be used as a surrogate for AUC, although the acceptable target trough concentration will vary depending on dosing interval and elimination rate constant. This work included development of an AUC-trough equation to establish a patient-specific target for steady-state trough concentration.

Overprescription of antibiotics in patients with community-acquired pneumonia in the intensive care unit.

PURPOSE: We aimed to assess factors associated with therapy failure in patients with community-acquired pneumonia in the intensive care unit (ICU). METHODS: Electronic charts of patients with International Classification of Diseases, Ninth Revision, codes of pneumonia who were admitted to the ICU at a tertiary academic medical center in Southern Arizona were reviewed. RESULTS: Antipseudomonal coverage and anti-methicillin-resistant Staphylococcus aureus (MRSA) coverage were often prescribed (58.4% and 54.1%, respectively). Antipseudomonal coverage was rarely necessary as pseudomonal pneumonia was found in only one case (0.9%). Antipseudomonal and anti-MRSA coverage was not associated with improved outcomes. CONCLUSION: Overprescription of antibiotics in this population remains a significant problem. More work is needed to further limit unnecessary antibiotic use.

Knowledge, attitude, and practices associated with the diagnosis and management of skin and soft-tissue infections among medical students, residents, and attending physicians.

Skin and soft-tissue infections (SSTIs) are commonly encountered by medical students, residents, and trainees. The Infectious Diseases Society of America (IDSA) has updated its recommendations regarding SSTI diagnosis and management in June 2014. We assessed knowledge, attitude, and practices toward diagnosis and management of SSTIs using an online survey. We disseminated the survey to medical students, residents, and attending physicians practicing in family and internal medicine department at a university-based hospital. A total of 103 surveys were completed out of 121 sent (85.1%) between July 2015 and March 2016. There were nine medical questions in the survey. The mean of correct answers was 4.5/9 ± 2.0. Medical knowledge correlated with the level of education (P < 0.001) but not with subspecialty (P = 0.97). Around 35% were familiar with the updated IDSA guidelines pertaining to SSTIs. The majority (85%) responded that the hospital staff would benefit from additional training and 75% agreed that more antibiotic stewardship education is needed. Our study shows that there are significant opportunities for development among students and physicians who encounter SSTIs.

Influenza vaccine availability at urgent care centers in the state of Arizona.

We surveyed urgent care centers (UCCs) in the state of Arizona to determine whether they offered the influenza vaccine during the 2016-2017 influenza season. Overall vaccine availability was 80.3% at these facilities. During this season, one-third of the UCCs offered influenza vaccination to children 6 months or older; approximately two-thirds offered influenza vaccination to children and young adults 16 years or older. This is the first study of influenza vaccine availability at UCCs.

Recurrence of urinary tract infections and development of urinary-specific antibiogram for kidney transplant recipients.

OBJECTIVES: Urinary tract infection (UTI) recurrence and antimicrobial resistance remain a common problem in kidney transplant recipients. Whilst the use of annual institutional antibiograms may help guide appropriate empirical antibiotic selection, these non-disease specific antibiograms do not always account for patient-specific risk factors or disease-specific resistance patterns. This study determined the frequency of UTI recurrence during the first year after kidney transplantation as well as differences in antimicrobial susceptibility between an institutional antibiogram and the disease-specific antibiogram for patients following kidney transplantation. METHODS: In this study, adult patients with at least one UTI during an inpatient admission within 1 year post kidney transplantation were evaluated. A disease-specific antibiogram for UTIs in kidney transplant recipients was prepared based on culture results and was compared with the annual institutional antibiograms. RESULTS: Of 299 kidney transplants performed during the study period, 66 subjects meet the study inclusion criteria, of whom 47% had two or more UTIs within the first year after kidney transplant. In comparison with the institutional antibiogram, Escherichia coli isolated from urine samples from kidney transplant recipients were significantly more resistant to trimethoprim/sulfamethoxazole, ceftriaxone, cefepime, ciprofloxacin and gentamicin (P<0.0001). CONCLUSIONS: Multiple UTIs are common in kidney transplant recipients during the first year post-transplantation. E. coli urinary isolates were significantly more resistant to multiple antibiotic drug classes in this patient population compared with the general hospital population. Antimicrobial stewardship programmes at transplant centres should consider producing disease-specific antibiograms specifically for transplant recipients to improve empirical antibiotic selection guidance.

Does Everything That's Counted Count? Value of Inflammatory Markers for Following Therapy and Predicting Outcome in Diabetic Foot Infection.

To assess the severity of inflammation associated with diabetic foot infection (DFI), values of inflammatory markers such as white blood count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR) are often measured and tracked over time. It remains unclear if these markers can aid the clinician in the diagnosis and management of DFI, and ensure more rational use of antibiotics. Hospitalized adult patients (n = 379) with DFI were retrospectively assessed for abnormal inflammatory markers, correlation between values of inflammatory markers, and clinical diagnosis on initial admission and on last follow-up. At admission, WBC, ESR and NLR were each elevated in patients with osteomyelitis and only ESR was significantly elevated in patients with soft tissue infection only. Only WBC was significantly elevated in patients with osteomyelitis compared with uninfected diabetic feet on last follow-up. Considering the predictive performance of these inflammatory markers, they demonstrated excellent positive predictive value at admission, and excellent negative predictive value at the last follow-up visit. Moreover, the number of elevated markers was further associated with probability of infection both at admission and last follow-up.

Improving the knowledge of students and physicians regarding appropriate use of antibiotics for respiratory infections through an online educational module.

We developed an interactive online module to improve the knowledge of students and physicians regarding respiratory infections. Our study showed that the completion of this module was associated with substantial improvement in knowledge, with modest retention after 2 months.

Point-of-care testing for infectious diseases: opportunities, barriers, and considerations in community pharmacy.

OBJECTIVES To identify opportunities to perform point-of-care (POC) testing and/or screening for infectious diseases in community pharmacies, provide an overview of such tests and how they are used in current practice, discuss how the Clinical Laboratory Improvement Amendments of 1988 (CLIA) affect pharmacists performing POC testing, and identify and discuss barriers and provide recommendations for those wanting to establish POC testing for infectious diseases services in community pharmacies. DATA SOURCES PubMed and Google Scholar were searched from November 2012 through May 2013 and encompassed the years 2000 and beyond for the narrative review section of this article using the search terms rapid diagnostic tests, POC testing and infectious diseases, pharmacy services, CLIA waiver, and collaborative drug therapy management. All state boards of pharmacy in the United States were contacted and their regulatory and legislative websites accessed in 2012 and January 2013 to review relevant pharmacy practice laws. DATA SYNTHESIS POC testing for infectious diseases represents a significant opportunity to expand services in community pharmacies. Pharmacist education and training are addressing knowledge deficits in good laboratory practices and test performance and interpretation. Federal regulations do not define the qualifications for those who perform CLIA-waived tests, yet few pharmacists perform such services. Fewer than 20% of states address POC testing in their statutes and regulations governing pharmacy. CONCLUSION POC testing for infectious diseases could benefit patients and society and represents an opportunity to expand pharmacy services in community pharmacies. Existing barriers to the implementation of such services in community pharmacies, including deficits in pharmacist training and education along with state regulatory and legislative variance and vagueness in statutes governing pharmacy, are not insurmountable.

Poor absorption of high-dose posaconazole in pediatric bone marrow transplant patients.

OBJECTIVE: To describe the use of high-dose posaconazole in 2 pediatric patients who received bone marrow transplant (BMT) and highlight concerns regarding posaconazole absorption. CASE SUMMARY: We present 2 pediatric BMT patients in whom prescribed high doses of posaconazole (120-300 mg/kg/day for >3 months) provided serum concentrations less than 1 µg/mL. Both patients received posaconazole with other antifungal therapy and surgical debridement for Rhizopus spp. infections after allogeneic BMTs. Various alternative dosing strategies to potentially enhance posaconazole absorption to increase serum concentrations were attempted, including higher daily doses, frequent or continuous oral administration via feeding tube, use of enteral nutrition, and limiting use of acid-blocking agents. During high-dose therapy, frequent posaconazole serum concentration measurement and other monitoring techniques, such as continuous telemetry, were used. While the fungal infections resolved in both patients and no serious adverse effects could be attributed to high-dose posaconazole administration, posaconazole therapy may have contributed to nausea and vomiting in 1 of the patients. DISCUSSION: These 2 cases describe complex circumstances, with several reasons that may have affected the patients' posaconazole serum concentrations. Both patients received significantly higher doses than those recommended in the posaconazole prescribing information, but potentially serious adverse events were not observed since serum concentration measurements were rarely more than 0.5 µg/mL. CONCLUSIONS: The safety of high-dose posaconazole therapy was not determined in these 2 patients. However, given that limited alternative therapy options are available for severely ill patients with suspected posaconazole malabsorption, research regarding dosing strategies should be considered.

Role of posaconazole in the treatment of oropharyngeal candidiasis.

Posaconazole is the newest azole antifungal approved by the US Food and Drug Administration, and possesses a broad spectrum of activity against numerous yeasts and filamentous fungi. It is available as an oral suspension and is generally well tolerated by patients, but gastrointestinal absorption is sometimes inadequate and remains a clinical concern in treating deep-seated infections. It is used routinely and effectively for the prophylaxis of invasive fungal infections in immunosuppressed hosts and is an effective treatment of oropharyngeal candidiasis, including azole-resistant disease.

End-of-procedure cefazolin concentrations after administration for prevention of surgical-site infection.

PURPOSE: The adequacy of end-of-procedure free cefazolin concentrations after administration for the prevention of surgical-site infection (SSI) and compliance with national guidelines for antimicrobial prophylaxis for SSI were assessed. METHODS: Patients undergoing elective surgery and receiving cefazolin for perioperative antimicrobial prophylaxis were prospectively enrolled. Antibiotic administration was controlled by the surgeon and usage was recorded. For each patient, a single blood sample for cefazolin serum free and total concentrations was obtained within 15 minutes of wound closure. A free serum concentration threshold of 4 microg/mL was arbitrarily chosen based on the minimum inhibitory concentration required to inhibit 90% of strains of methicillin-susceptible Staphylococcus aureus and Escherichia coli. RESULTS: Fifty-seven subjects were enrolled, and noncompliance with published guidelines was observed for 26% of patients. Forty-six subjects had serum samples available for assay, 21.7% of whom had end-of-procedure free cefazolin concentrations of <4 microg/mL. Results of multivariate regression and population pharmacokinetic analysis revealed the importance of age and lean body weight in cefazolin clearance. Younger and taller patients had a greater risk of achieving below-threshold end-of-procedure concentrations. Of the patients for whom published guidelines were not followed, 67% had end-of-procedure free cefazolin concentrations below the threshold concentration (4 microg/mL). In contrast, less than 15% of cases where SSI prophylaxis complied with the published guidelines had below-threshold concentrations at the end of surgery. CONCLUSION: Noncompliance with antimicrobial prophylaxis guidelines was associated with low end-of-procedure antibiotic levels. Compliance with guidelines did not guarantee adequate levels.

Estimation of creatinine clearance in end-stage liver disease.

BACKGROUND: Estimation of renal function in patients with end-stage liver disease (ESLD) is complicated by several factors. OBJECTIVE: To develop a practical and relatively inexpensive method for estimating creatinine production and clearance in patients with ESLD. METHODS: Serum creatinine concentrations and urinary excretion of creatinine were measured in 27 patients with moderate-to-severe liver disease with the goal of developing equations to predict creatinine clearance from serum creatinine. Subjects were studied during an initial evaluation for a liver transplant program. Two 24 hour urine specimens were collected along with 3 serum samples over a 2 day evaluation period. Serum and urine creatinine concentrations were determined using both a modified Jaffé (autoanalyzer) method and an HPLC method. The data were analyzed using nonlinear mixed-effects modeling. RESULTS: Considering both statistical criteria and physiological conventions through allometric scaling theory, creatinine clearance (mL/min) in males can be estimated as (80/serum creatinine) x (actual body weight/70)0.75. For females, the same equation is valid, but the result is multiplied by 0.661. A simplified equation without the exponent is presented, along with equations that are appropriate when an HPLC assay is used for greater specificity. CONCLUSIONS: These equations offer potential for improved estimation of creatinine clearance in patients with liver impairment; however, they need further validation using an independent group of subjects.

Effect of ertapenem protein binding on killing of bacteria.

The effect of protein binding on the antimicrobial activity of ertapenem was evaluated using the bacterial kill rate and concentration-response studies. Various proportions of human serum were utilized to determine the total and free-drug concentrations using a validated high-performance liquid chromatography assay. The MICs and kill curves were determined for test isolates of Enterobacter cloacae and Staphylococcus aureus at various percentages of human serum. The killing of bacteria was analyzed in relation to the free and total concentrations of ertapenem at various proportions of human serum. It was determined that unbound ertapenem was responsible for the antimicrobial activity against the test isolates.