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

Management of Carbapenem-resistant Acinetobacter Baumannii Skin and Soft Tissue Infections

CRAB can cause complicated SSTIs in the setting of burns or combat-related wounds, as well as in patients with morbid obesity, cirrhosis, immunosuppression, and diabetes mellitus.[59,60] A. baumannii has a number of resistance mechanisms including all four classes of β-lactamases, AMEs, and efflux pumps.[61] CRAB is associated with a significantly higher risk of mortality than patients with carbapenem-susceptible isolates, which is in part because of the inappropriate antimicrobial treatment.[62]

Despite the diminishing antibacterial options for CRAB SSTIs, there are no specific guidelines for their management. The first-line agents are polymyxins; however, colistin-resistant A. baummanii can be found in as high as 50% of CRAB.[63,64] Tetracyclines, such as minocycline and tigecycline, have been used,[65] although rising resistance and increased mortality associated with tigecycline have made it a last resort option for CRAB.[66]

Combination therapy in the management of CRAB was shown to improve patient outcomes in some clinical studies.[67–70] However, a recent randomized controlled trial (RCT) showed that monotherapy with colistin was noninferior to a combination therapy with a carbapenem and colistin with regard to mortality in severe CRAB infections.[71] Moreover, a subgroup analysis of colistin-resistant CRAB isolates in this study found that the colistin–meropenem arm was associated with a higher mortality compared with the colistin arm.[72] Another recent study of CRAB bacteremia found that the combined therapy with high-dose colistin and standard-dose tigecycline was not associated with a reduction in mortality compared to colistin monotherapy.[73] However, the use of colistin results in challenges including renal toxicity, difficulty achieving adequate and consistent plasma levels, and rising resistance rates, which emphasize the need for alternative therapeutic options.[66]

Cefiderocol is likely to be the first new agent active against CRAB that is expected to be approved for clinical use.[74,75] A study on cUTIs showed noninferiority of intravenous cefiderocol to imipenem–cilastatin in patients with MDR-GNB infections[14] and another found that it exhibited more potent in vitro activity than ceftolozane–tazobactam and ceftazidime–avibactam against CRAB.[76]

Other novel agents include eravacycline, which has shown in-vitro activity against tetracycline-resistant A. baumannii isolates, with limited activity against isolates expressing the efflux pump AdeABC. A recent study found that the addition of sulbactam to cefoperazone could increase the in-vitro antibacterial activity against CRAB.[77] Lastly, plazomicin may play a role in combination therapy with carbapenems against CRAB.[78]

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