Plazomicin is a novel aminoglycoside antibiotic that binds to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis in a concentration‐dependent manner. Plazomicin displays a broad spectrum of activity against aerobic gram‐negative bacteria including extended‐spectrum β‐lactamase–producing Enterobacteriaceae, carbapenem‐resistant Enterobacteriaceae, and organisms with aminoglycoside‐modifying enzymes. In a large phase III clinical trial, plazomicin was shown to be noninferior to meropenem in the treatment of complicated urinary tract infections (cUTIs) with respect to the coprimary efficacy end points of the microbiologically modified intent‐to‐treat composite cure rate at day 5 (plazomicin 88% [168/191 subjects] vs meropenem 91.4% [180/197]) and at the test‐of‐cure visit (plazomicin 81.7% [156/191] vs meropenem 70.1% [138/197]). In a small phase III clinical trial, plazomicin was shown to be effective in the treatment of infections caused by carbapenem‐resistant Enterobacteriaceae. It was associated with a lower all‐cause mortality or significant disease‐related complication rate (23.5% [4/17]) compared with colistin (50% [10/20]). The most common adverse reactions associated with plazomicin are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting, and hypotension. As with other aminoglycosides, plazomicin may cause neuromuscular blockade, ototoxicity, and fetal harm in pregnant women. Due to limited efficacy and safety data, plazomicin is indicated for the treatment of cUTIs in adults with limited or no alternative treatment options, using a dosage regimen of 15 mg/kg intravenously every 24 hours for 4–7 days. Dosage reductions and therapeutic drug monitoring are warranted in patients with moderate or severe renal impairment. Plazomicin is not recommended in patients with severe renal impairment including those receiving renal replacement therapy. With the approval of plazomicin, clinicians now have an additional option for the treatment of adults with cUTIs, particularly those caused by multidrug‐resistant gram‐negative rods.
M/V has a valuable role in the treatment of CRE and should be used judiciously to preserve its use for resistant infections.
Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.
Background- Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection seen in immunosuppressed patients, including solid-organ transplant recipients. Sulfamethoxazole/trimethoprim (SMX/TMP) has long been considered first-line therapy for PCP prophylaxis. Optimal dosing regimens in solid-organ transplant recipients have not been fully defined. Objective-To examine the tolerability of a 1-year, 3-times weekly, prophylactic regimen of a single-strength SMX/TMP tablet. Study Design-Single-center, retrospective cohort study. Setting-A tertiary-care medical center, including inpatient hospitalizations and outpatient transplant clinic visits. Patients-Adult patients who received a kidney transplant between December 1, 2010, and November 30, 2012, at Hartford Hospital. Patients receiving a concurrent extrarenal transplant were excluded. Patients' charts were reviewed for up to 1 year after transplant. Results-A total of 88 patients were included in the analysis. Sixty-seven patients finished a full year of SMX/TMP after transplant, 10 patients discontinued SMX/TMP less than 1 year after transplant, and 11 patients started taking atovaquone instead of SMX/TMP after transplant. Documented reasons for discontinuation included hyperkalemia, leukopenia, diarrhea, and simplification of medication regimen. Patients without a documented reason for discontinuation did not have any obvious anomalies in laboratory values that would account for the discontinuation. Patients who received atovaquone for PCP prophylaxis had higher rates of recurrent urinary tract infections than did patients who received SMX/TMP for prophylaxis (33% vs 7%, P = .02). A longer postoperative stay (median [interquartile range, IQR] 13 [8.25-26] days vs 7 [6-9.5] days, P = .02), higher rates of delayed graft function (50% vs 10%, P = .004), as well as higher serum creatinine levels on postoperative day 7 (6.25 [2.4-10.1] mg/dL vs 1.8 [1.2-4.2] mg/dL, P= .01), postoperative month 1 (1.9 [0.8] mg/dL vs 1.4 [0.5] mg/dL, P = .002), and postoperative month 12 (1.6 [0.5] mg/dL vs 1.3 [0.3] mg/dL, P = .04) were associated with early SMX/TMP discontinuation. Conclusion-A low-dose prophylactic SMX/TMP regimen of 1 single-strength tablet 3 times weekly is well tolerated. Discontinuation rates were lower than other rates reported for higher-dose regimens.
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