Double-carbapenem therapy in the treatment of multidrug resistant Gram-negative bacterial infections: a systematic review and meta-analysis

Abstract

Background: To compare the efficacy and safety of double-carbapenem therapy (DCT) with other antibiotics for the treatment of multidrug resistant (MDR) Gram-negative bacterial infections. Methods: Cochrane Library, PubMed, Embase and Web of Science as well as Chinese databases were searched from database establishment to February 2019. All types of studies were included if they had evaluated efficacy and safety of DCT regimens in patients with MDR Gram-negative bacterial infections. Clinical response, microbiological response, adverse events and mortality were the main outcomes. The protocol was registered with PROSPERO No. CRD42019129979. Results: Three cohort or case-control studies consisting of 235 patients and 18 case series or case reports consisting of 90 patients were included. The clinical and microbiological responses were similar between DCT and other regimens in patients with carbapenem-resistant Enterobacteriaceae (CRE) infection. DCT achieved a lower mortality than comparators in patients with CRE infection (OR = 0.44, 95% CI = 0.24-0.82, P = 0.009). Ertapenem was the most reported antibiotic in DCT regimens in case series or case reports. Moreover, clinical and microbiological improvements were found in 59 (65.6%) and 63 (70%) in total 90 cases, respectively. Conclusions: DCT was as effective as other antibiotics in treating MDR Gram-negative bacterial infections, with similar efficacy response and lower mortality. DCT could be an alternative therapeutic option in the treatment of MDR Gram-negative bacterial infections. High-quality randomized controlled trials were required to confirm the beneficial effects of DCT.

Risk Factors and Outcomes for Multidrug-resistant Gram-negative Bacterial Infection in Adult Patients with Abdominal Surgery Requiring Intensive Care

“…The agents of last resort against MDR organisms include the tigecycline, aminoglycosides and polymyxins particularly carbapenem-resistant isolates, but it can be also associated with more signi cant adverse effects (i.e., nephrotoxicity, ototoxicity, and neurotoxicity) [44][45][46][47][48][49][50]. Consideration of therapeutic effectiveness and adverse effects, combination therapy, at least in the empirical phase of treatment, is the higher probability that a MDR isolate will be susceptible to at least one agent in combination regimens and minimize the adverse effects [51,52]. Before the development of novel antimicrobials that could provide clinical e cacy towards MDR organisms, multiple interventions should be employed to control the spreading of MDR organisms including antimicrobial stewardship policies and appropriate infection control measures [13,14].…”

Perfil de utilização e custos de carbapenêmicos em uma unidade de terapia intensiva de um hospital público do Distrito Federal – Brasil

“…Os efeitos da terapia com duplo carbapenêmico são descritos por vários estudos in vitro apesar de ainda haver pouca literatura que fundamente e discuta desfechos clínicos resultantes dessa associação in vivo (White et al, 2019). Li et al (2020) em revisão sistemática referem que, devido à resposta clínica semelhante a outras alternativas e menor mortalidade, a terapia de duplo carbapenêmico pode corresponder a uma opção para tratamento de infecções causadas por bactérias gram-negativas resistentes (Li et al, 2020). Entretanto, mais estudos são necessários, principalmente com ensaios clínicos de maior qualidade que abordem desfechos relacionados à efetividade, segurança do paciente e risco de resistência do microrganismo (Li et al, 2020).…”

Ceftolozane/Tazobactam and Ceftazidime/Avibactam for Multidrug-Resistant Gram-Negative Infections in Immunocompetent Patients: A Single-Center Retrospective Study

“…Actual therapeutic strategies are to increase the doses of carbapenem, colistin, and tigecycline or to combine these drugs. Double-carbapenem therapy was adopted as a salvage therapy for critically ill patients with CRE or CPE infections [ 19 , 20 ], but the evidence about this therapeutic option is low [ 21 , 22 ]. Ceftazidime/avibactam and ceftolozane/tazobactam could be useful in the management of carbapenem-sparing programs in settings with a high prevalence of ESBL-producing Enterobacterales and DTR Gram-negative infections.…”