Kathryn R. Matthias

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.

Effect of Ertapenem Protein Binding on Killing of Bacteria

ABSTRACT 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.

Should tigecycline be considered for urinary tract infections? A pharmacokinetic re-evaluation

platelets plus amphotericin B achieved significantly greater inhibition of the germination rate (P,0.05) than did amphotericin B or platelets alone (Figure 1a). The effect was additive. These results were found with both tested amphotericin B concentrations, although 1 mg/L revealed a better inhibitory effect than the lower concentration (Figure 1a). With caspofun-gin, the germination rate was not significantly reduced (Figure 1b). When azoles were used in combination with plate-lets, the inhibitory effect was found to be additive in comparison with either azole or platelets alone (Figure 1c and d). As found for the germination rate, human platelets plus amphotericin B achieved significantly greater inhibition of hyphal elongation (P,0.05) than amphotericin B or platelets alone. Hyphal elongation was significantly reduced in all tested aspergilli, either under platelet or caspofungin treatment. When used in combination, the effect was found to be additive. The combination of platelets plus either azole at any concentration tested did not significantly enhance the reduction of hyphal elongation. Platelets decreased the ability of hyphae to reduce XTT; however, the combination of platelets plus antimycotics had no additive effect on hyphal damage (data not shown). Our findings indicate that platelets in combination with anti-mycotics exert additive effects in reducing the germination rate and hyphal elongation of A. fumigatus in vitro. Among the tested antimycotic substances, amphotericin B revealed the best results in combination with human platelets. However, platelets plus antimycotics were not additive for hyphal damage. In the immunocompromised patient, inhaled Aspergillus conidia germinate into hyphae, 1 the growing and invading structures of filamentous fungi. Consequently, blocking fungal germination and delaying hyphal growth is crucial in preventing invasive disease. In our study, the combination of platelets plus amphotericin B synergistically enhanced the antifungal activity (P,0.05) in reducing germination rate and hyphal elongation. Amphotericin B is known to complex with sterols in the fungal cell membrane, 4 leading to pore formation and increased cell membrane permeability. This could support the antifungal activity of human platelets, by enabling the penetration of antifungal platelet factors. 5 A clinical study showed that patients with invasive fungal disease had a significantly longer duration of thrombocytopenia compared with those without infection, 6 suggesting that the low platelet count is related to the infection. Our in vitro data suggest that a normal platelet count contributes to overcome fungal infections and that platelets are capable of enhancing the efficacy of antimycotics. 3 Perkhofer S, Kehrel BE, Dierich …

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) × (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.

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.

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.

Urinary Tract Infections Recurrence 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.

Appropriateness of Ciprofloxacin Dosing Based on a Population Pharmacokinetic Model

Purpose Over the past two decades, the minimum inhibitory concentrations (MICs) of ciprofloxacin have been steadily increasing for gram-negative bacteria. One major reason cited for this “MIC creep” is underdosing of ciprofloxacin due to a lack of understanding of its pharmacodynamic properties. The primary objective of this study was to evaluate the frequency of underdosing of ciprofloxacin in a tertiary acute care medical center based on a population pharmacokinetic model. Secondary objectives included evaluation of appropriateness of dosing based on renal function and approved product labeling. Methods Seventy-six patients were included in this single-center, retrospective study. Data collection included demographic, laboratory, and microbiology data along with details on antibiotic administration. Patient-specific predicted 24-hour area under the curve/MIC (AUC24/MIC) values were estimated using a population pharmacokinetic model with a goal predicted AUC24/MIC of at least 100 and a preferred target value of 250. Results Only 8% of the subjects obtained a predicted AUC24/MIC higher than 250, while 34% of the subjects achieved a predicted AUC24/MIC of 100 or less. The majority of patients (79%) received a total daily intravenous-equivalent dose of 800 mg, whereas only 8% of subjects received an initial total daily intravenous-equivalent dose of 1,200 mg, which is the recommended dose for most severe infections. Overall 26% of subjects were prescribed an appropriate initial dose for their estimated renal function based on infection type and severity. Conclusion Ciprofloxacin for acute infection treatment was frequently underdosed based on US Food and Drug Administration–approved labeling and estimated predicted AUC24/MIC at a tertiary acute care medical center.

Significance of bacteriuria in patients with end-stage renal disease on hemodialysis

The significance of bacteriuria in patients with end-stage renal disease (ESRD) on hemodialysis (HD) is unclear. It is not known whether treatment of asymptomatic bacteriuria is associated with lower rates of urinary tract infection or readmission. Adult patients with ESRD on HD were retrospectively evaluated to assess factors associated with the recurrence of bacteriuria and readmission. We included 68 patients in the analysis. There were 20 patients (29.4%) with urinary symptoms. All symptomatic patients received antibiotic therapy, whereas half of the asymptomatic patients received antibiotics. Antibiotic use was not associated with lower rates of readmission or the recurrence of bacteriuria.

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

HIGHLIGHTSUrgent care centers are an emerging source of ambulatory healthcare in the United States.Influenza vaccination is not routinely available at these facilities in Arizona.This is the first study to investigate influenza vaccination at urgent care centers. &NA; 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.