Treatment of Multidrug-resistant Gram-Negative Skin and Soft Tissue Infections

Jean-Francois Jabbour; Sima L. Sharara; Souha S. Kanj

Disclosures

Curr Opin Infect Dis. 2020;33(2):146-154. 

In This Article

Abstract and Introduction

Abstract

Purpose of review:The increase in skin and soft tissue infections (SSTI) because of multidrug-resistant (MDR) pathogens is a global concern. Although MDR Gram-negative bacteria (GNB) are often overlooked as a cause of SSTIs, their burden on the morbidity of many subgroups of patients is high. There is a paucity in the available treatment options and guidelines on how to treat these pathogens. This manuscript reviews the management of SSTIs caused by carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa (CRPA), Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. We also highlight a few novel antibiotics that show promise in the future management of MDR-GNB SSTIs.

Recent findings: Studies on treatment options of MDR-GNB SSTIs are scarce. Most clinical trials investigating new antibiotics have addressed conditions such as complicated intraabdominal infections, complicated urinary infections, and respiratory infections. CREs are a heterogenous group of pathogens with various mechanisms of resistance dictating susceptibility to different antimicrobial agents. Ceftazidime–avibactam, and meropenem–vaborbactam have potent activity against some of the CREs, especially Klebsiella pneumoniae carbapenemase (KPC) producers. Several novel antibiotics have potent activity against CRPA SSTIs, such as ceftazidime–avibactam, ceftolozane–tazobactam, cefiderocol, delafloxacin, finafloxacin, and murepavadin. Cefiderocol may also play an important role in the management of CRAB SSTIs, along with plazomicin and eravacycline.

Summary: MDR-GNB play a major role in SSTIs in patients with underlying immunodeficiency, as well as burn or trauma-related injuries. With the alarming global rise in MDR-GNB resistance, antibiotic therapy for SSTIs is challenging and must be guided by in-vitro susceptibility results. Currently, data extrapolated from other indications and combination therapy can be used empirically pending microbiological data and susceptibilities. Novel antibiotics are currently under development. It is hoped that future clinical trials will be designed to address MDR-GNB SSTIs.

Introduction

Multidrug resistance (MDR) in Gram-negative bacteria (GNB) causing serious infections is a global problem and a major cause of morbidity and mortality.[1] SSTIs caused by MDR-GNB are increasingly seen in clinical practice, especially in patients with diabetes mellitus, severe and chronic infections, immunosuppression, prolonged hospitalization, and following traumatic and war injuries.[1,2] Table 1 summarizes the patients at risk for MDR-GNB SSTI and the most likely infecting pathogens.

The rise of resistance limits the options for effective treatment of SSTIs caused by MDR-GNB. Guidelines for SSTI treatment are set by many societies, and adherence to these recommendations, such as those set by the Infectious Diseases Society of America in 2014, result in a reduction of treatment failure rates.[3] All current guidelines, however, have failed to include specific recommendations on the directed antimicrobial therapy against MDR-GNB causing SSTIs. This review highlights the role of MDR-GNB in SSTIs and offers an update on the suggested current treatment options. Duration of therapy will not be specifically addressed, as this is highly dependent on the underlying host, extent of disease, surgical debridement, and response to therapy.

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