Lindsay Petty

Cobicistat Significantly Increases Tacrolimus Serum Concentrations in a Renal Transplant Recipient with Human Immunodeficiency Virus Infection

Cobicistat is a pharmacokinetic booster in several fixed‐dose combination products for treatment of human immunodeficiency virus (HIV) infection. As a potent inhibitor of cytochrome P450 (CYP) 3A enzymes, significant drug‐drug interactions are expected between cobicistat and medications that are metabolized primarily through the CYP3A pathway, including calcineurin inhibitors (e.g., tacrolimus and cyclosporine). We describe a case of tacrolimus toxicity due to supratherapeutic tacrolimus concentrations when Stribild (elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate) was initiated for newly diagnosed HIV infection in a 50‐year‐old renal transplant recipient who was previously receiving a stable tacrolimus regimen. Drug‐drug interaction via CYP3A inhibition was acknowledged, and weekly labs were ordered to allow for close monitoring of renal function and tacrolimus serum concentrations as recommended by Stribild prescribing information. The patient reported headache, insomnia, stomachache, and decreased urine output within 1 week of starting Stribild and was found to have acute kidney injury (serum creatinine [Scr]concentration increasing from 1.5–2.3 mg/dl) and a serum tacrolimus concentration of 111.2 ng/ml at 1 week follow‐up (goal trough level 4–6 ng/ml). Both tacrolimus and Stribild were withheld. In 15 days, the patients tacrolimus serum concentration returned to goal. In the interim, he required twice/week clinic visits for laboratory assessments and an emergency department visit for management of hyperkalemia (potassium 6.5 mEq/L). Triumeq (abacavir, dolutegravir, and lamivudine) was started about 4 weeks later after Scr returned to baseline, and his tacrolimus serum trough concentrations subsequently remained stable. To our knowledge, this is the first case report describing the extent, significance, and onset of cobicistat and tacrolimus drug‐drug interaction in clinical practice. As more fixed‐dose combination products including cobicistat as a pharmacokinetic booster come to market, clinicians should be reminded of its multitude of clinically significant drug‐drug interactions.

Human immunodeficiency virus and coinfection with hepatitis B and C.

In HIV-infected individuals, coinfection with HBV and/or HCV is common because of shared modes of transmission. It is known that HIV accelerates progression of liver disease and results in increased morbidity and mortality associated with viral hepatitis, but it is less clear if viral hepatitis has a direct effect on HIV. Treatment of viral hepatitis improves outcomes and should be considered in all HIV-infected patients. Treatment of HBV without concurrent treatment of HIV is risky because resistance can occur in both viruses if regimens are not carefully chosen.

Candida dubliniensis Pneumonia: A Case Report and Review of Literature

Candida dubliniensis is an uncommon species of Candida which has been implicated in fungal pneumonia only very rarely. We present the case of a 75-year-old man with laryngeal cancer undergoing chemotherapy on broad-spectrum antibiotics and tuberculosis therapy with blood and endotracheal cultures positive for C. dubliniensis. Subsequent autopsy was performed with postmortem lung cultures positive for C. dubliniensis and lung histopathology demonstrating an invasive fungal infection. Molecular analysis of the lung tissue confirmed the identity of the fungi as C. dubliniensis. Since its discovery as a pathogen in the oral cavities of HIV-positive patients, C. dubliniensis has been identified in a wide spectrum of clinical scenarios and anatomic locations but manifests only rarely as pneumonia. This report represents a novel case of C. dubliniensis pneumonia confirmed by culture, histopathology, and molecular identification.

Cardiac toxoplasmosis after heart transplantation diagnosed by endomyocardial biopsy

We describe a case of cardiac toxoplasmosis diagnosed by routine endomyocardial biopsy in a patient with trimethoprim‐sulfamethoxazole (TMP‐SMX) intolerance on atovaquone prophylaxis. Data are not available on the efficacy of atovaquone as Toxoplasma gondii prophylaxis after heart transplantation. In heart transplant patients in whom TMP‐SMX is not an option, other strategies may be considered, including the addition of pyrimethamine to atovaquone.

A case of Q fever after liver transplantation

Coxiella burnetii, the causative agent of Q fever, is a zoonosis that causes both acute and chronic disease in humans. Few cases have been reported in solid organ transplant recipients, and this case highlights the need to include Q fever in the differential diagnosis for fever of unknown origin in solid organ transplant hosts.

Repeated Blood Cultures in Pediatric Febrile Neutropenia: Would Following the Guidelines Alter the Outcome?

The Infectious Diseases Society of America (IDSA) guidelines recommend collecting blood cultures for the first 3 days of febrile neutropenia (FN) in the clinically stable oncology patient with persistent fevers. Nonetheless, many physicians send daily blood cultures beyond 3 days, and the impact of that practice is uncertain.

The Importance of a Complete Social History

A 48-year-old man with a history of well-controlled human immunodeficiency virus infection and squamous cell cancer at the base of the tongue in remission presented to the Infectious Diseases Clinic with a lesion on his left hand. He reported noticing the lesion approximately 2 months prior to presentation. It began as a small nodule that slowly increased in size and later developed a central area of skin breakdown. He did not recall any trauma from around the time he first noticed the lesion. He denied any pain or drainage.

Overview of meropenem-vaborbactam and newer antimicrobial agents for the treatment of carbapenem-resistant Enterobacteriaceae

There has been a worldwide increase in infections caused by drug-resistant Gram-negative pathogens, including carbapenem-resistant Enterobacteriaceae (CRE). Meropenem-vaborbactam, a carbapenem antibiotic and novel boronic acid-based beta-lactamase inhibitor, is a fixed-dose combination product with potent in vitro activity against Enterobacteriaceae that are Klebsiella pneumoniae carbapenemase producers. Meropenem-vaborbactam has been studied in two Phase III trials, Targeting Antibiotic Non-susceptible Gram-negative Organisms (TANGO)-I and TANGO-II. TANGO-I was a multicenter, international Phase III, randomized, double-blind, double-dummy, active-control trial to evaluate the efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infection, including acute pyelonephritis. Among patients with complicated urinary tract infection and growth of a baseline pathogen, meropenem-vaborbactam was determined to be superior to piperacillin-tazobactam based on the composite outcome of symptom improvement or resolution and microbial eradication at the end of intravenous therapy. TANGO-II was a multicenter, international, Phase III, randomized, prospective, open-label, comparative trial to evaluate the efficacy and safety of meropenem-vaborbactam vs best available therapy for CRE infections. Treatment with meropenem-vaborbactam resulted in higher rates of clinical cure at the end of therapy (64.3%vs 33.3%, P=0.04). Additionally, 28-day all-cause mortality was 17.9% in the meropenem-vaborbactam group compared to 33.3% in the best available therapy group, a relative risk reduction of 46.5% (P=0.03). In addition to meropenem-vaborbactam, three other agents with activity against CRE are in late-stage development: imipenem-relebactam, plazomicin, and cefiderocol. The data from Phase II and III studies will help to further define the role of these agents. Overall, the recent approval of meropenem-vaborbactam and the active pipeline for other agents with broad Gram-negative activity are encouraging developments on the CRE therapeutic front.

A Multi-Faceted Antimicrobial Stewardship Program (ASP) Intervention Using Clinical Pharmacists Reduces Antibiotic Use and Hospital-Acquired Clostridium difficile Infection (HA-CDI)

Abstract Background ASPs continue to investigate novel ways to improve appropriate antibiotic utilization. The impact of an ASP-led, multi-faceted coaching and real-time feedback model directed towards clinical pharmacists was evaluated. Methods A single-center, pre-post quasi-experimental study was conducted with a four-month historical control period (11/2016–2/2017) and four-month intervention period (4/2016–7/2016) to reduce the use of ceftriaxone, fluoroquinolones, and clindamycin. Clinical pharmacists were responsible for ensuring the appropriate use of these restricted antimicrobials with limited guidance by the ASP in the historical control period. The intervention was multi-faceted: ASP pharmacists provided daily coaching and feedback on use of targeted agents to the clinical pharmacists, clinical pharmacists made recommendations to optimize therapy, and in-person monthly sessions were held where a dashboard consisting of aggregated utilization data and HA-CDI rates was discussed by the ASP pharmacist. Segmented regression analysis was used to determine the significance of this intervention on the utilization of the antibiotics, measured by days of therapy (DOT) per 1000 patient-days (PD). Rates of HA-CDI were also compared between the groups. Results The use of fluoroquinolones (34.4 vs. 26.2 DOT/1000 PD; Δ -23.9%), ceftriaxone (17.7 vs.. 13.6 DOT/1000 PD; ∆ -23.2%), and clindamycin (18.7 vs.. 13.3 DOT/1000 PD; ∆ -28.9%) decreased during the intervention period. Using segmented regression analysis, a significant decreasing rate of antibiotic use of all three agents was observed during the intervention period (Table). A significant decreasing rate of HA-CDI was also seen (rate ratio (RR): 0.787, 95% CI: 0.743–0.833, P < 0.001). Conclusion A multi-faceted coaching and feedback intervention targeting clinical pharmacists with substantial ASP oversight can significantly reduce inappropriate antibiotic use and HA-CDI in a large hospital.Table Segmented Regression Analysis Drug Effect Rate Ratio 95% CI P-value Fluoroquinolones Intervention*time 0.971 0.949–0.995 0.016 Ceftriaxone Intervention*time 0.842 0.795–0.891 <0.001 Clindamycin Intervention*time 0.931 0.904–0.958 <0.001 Disclosures G. Eschenauer, Merck: Grant Investigator, Research grant; V. D. Marshall, Merck: Grant Investigator, Research grant