Efficacy and safety of intravenous fosfomycin for the treatment of difficult-to-treat Gram-negative bacterial infections.

We reviewed the efficacy and safety of intravenous (IV) fosfomycin for the treatment of infections caused by Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR). Data were retrospectively retrieved for all hospitalized patients who received IV fosfomycin for ≥48 h for the treatment of a DTR GNB between September 27, 2017 and January 31, 2020. A total of 30 patients were included, of which 63.3% were males, and the median age was 63.5 years (IQR 46-73). The median Charlson Comorbidity Score was 6 (IQR 3.8-9). The urinary tract (56.7%) was the most frequent site of infection, and the most frequent target organisms were Klebsiella pneumoniae (56.7%), and Escherichia coli (23.3%). The majority (76.%) received IV fosfomycin in combination with other antibacterial agents. Clinical improvement was observed in 22 (73.3%), eradication of baseline pathogens in 20 (66.7%), 30-day all-cause mortality in 7 (23.3%), and documented emergent resistance to fosfomycin in 5 (16.7%) patients. Treatment-related adverse events were infrequent and generally mild or moderate in severity. In conclusion, IV fosfomycin is a potentially efficacious and safe treatment option for the treatment of DTR GNB infections. Randomized trials are urgently required to confirm the utility of IV fosfomycin as monotherapy and in combination with other agents.

Successful Use of Rifamycin-Sparing Regimens for the Treatment of Active Tuberculosis in Lung Transplant Recipients.

OBJECTIVES: Tuberculosis is an important opportunist infection that can complicate the posttransplant course of solid-organ transplant recipients. Lung transplant recipients are at higher risk of tuberculosis after transplant than are other solid-organ transplant recipients. Significant drug-drug interactions between antituberculous medications, especially rifampin, and immunosuppressant medications render treatment in this patient population especially challenging. Data on the management of tuberculosis in lung transplant recipients with rifamycin-sparing regimens are so far limited. Therefore, we evaluated the incidence, clinical features, treatment, and outcomes of active tuberculosis in lung transplant patients from a single center in Riyadh, Saudi Arabia. MATERIALS AND METHODS: Cases of active tuberculosis in lung transplant recipients diagnosed between January 2005 and December 2017 at our center were included. Data on patient demographics, clinical presentations, diagnosis, treatment regimens, and outcomes were collected. RESULTS: Seven of 133 lung transplant recipients (5.3%) were diagnosed with active tuberculosis during the study period, corresponding to an incidence rate of 2147/100 000 person-years. Patients were diagnosed at median time of 94 days posttransplant. Fever and weight loss were the most common presenting symptoms. All patients were initially treated with a regimen consisting of isoniazid, ethambutol, pyrazinamide, and moxifloxacin. Isoniazid was later substituted with rifabutin in 2 patients with isoniazid-resistant tuberculosis. All patients were treated for a total of 9 to 12 months, without any adverse event-related interruptions. All patients were alive at 12 months after the diagnosis of tuberculosis. There was no evidence of relapse in any of the patients after a median of 32 (range, 9-51) months of follow-up after treatment. CONCLUSIONS: Rifamycin-sparing regimens appear to be safe and highly efficacious in the treatment of active tuberculosis in lung transplant recipients.

Update on colistin in clinical practice.

Considerable progress has been made in the last decade towards better understanding of the optimal clinical use of colistin. It has become evident that higher intravenous (iv) colistin methanesulfonate (CMS) doses are important, probably with the addition of a loading dose in critically ill patients. Higher CMS doses lead to increased risk of nephrotoxicity, which seems reversible in most cases. Intravenous colistin is reasonably efficacious, but should continue to be considered only in the absence of safer alternatives. Although theoretically appealing, there is insufficient evidence to support inhaled colistin mono-therapy in non-cystic fibrosis patients. Moreover, the balance of evidence available at present is not in favor of adjunctive inhaled colistin therapy. Intrathecal or intra-ventricular colistin administration are appropriate options for neurosurgical meningitis caused by colistin-susceptible, multidrug resistant gram-negative bacteria. Ongoing randomized, controlled trials will hopefully help decide if combining colistin with a carbapenem, fosfomycin, or rifampicin is of clinical advantage.