Stefano Di Bella1, Daniele Roberto Giacobbe2, Alberto Enrico Maraolo3, Valentina Viaggi4, Roberto Luzzati5, Matteo Bassetti6, Francesco Luzzaro4, Luigi Principe4. 1. Clinical Department of Medical, Surgical and Health Sciences. Trieste University, Trieste, Italy. Electronic address: stefano932@gmail.com. 2. Clinica Malattie Infettive, Ospedale Policlinico San Martino IRCCS, Genoa, Italy. 3. First Division of Infectious Diseases, Cotugno Hospital, AORN dei Colli, Naples, Italy. 4. Clinical Microbiology and Virology Unit, 'A. Manzoni' Hospital, Lecco, Italy. 5. Clinical Department of Medical, Surgical and Health Sciences. Trieste University, Trieste, Italy. 6. Clinica Malattie Infettive, Ospedale Policlinico San Martino IRCCS, Genoa, Italy; Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
Abstract
OBJECTIVES: Ceftazidime/avibactam (CAZ-AVI), approved in 2015, is an important first-line option for Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC-E). Although still uncommon, resistance to CAZ-AVI has emerged and may represent a serious cause of concern. METHODS: We performed a systematic literature review of clinical and microbiological features of infections and colonisations by CAZ-AVI-resistant KPC-E, focused on the in vivo emergence of CAZ-AVI resistance in different clinical scenarios. RESULTS: Twenty-three papers were retrieved accounting for 42 patients and 57 isolates, mostly belonging to K. pneumoniae ST258 harbouring D179Y substitution in the KPC enzyme. The USA, Greece and Italy accounted for 80% of cases. In one-third of isolates resistance was not associated with previous CAZ-AVI exposure. Moreover, 20% of the strains were colistin-resistant and 80% were extended-spectrum β-lactamase (ESBL)-producers. The majority of infected patients had severe underlying diseases (39% cancer, 22% solid-organ transplantation) and 37% died. The abdomen, lung and blood were the most involved infection sites. Infections by CAZ-AVI-resistant strains were mainly treated with combination therapy (85% of cases), with meropenem being the most common (65%) followed by tigecycline (30%), gentamicin (25%), colistin (25%) and fosfomycin (10%). Despite the emergence of resistance, 35% of patients received CAZ-AVI. CONCLUSION: Taken together, these data highlight the need for prompt susceptibility testing including CAZ-AVI for Enterobacterales, at least in critical areas. Resistance to CAZ-AVI is an urgent issue to monitor in order to improve both empirical and targeted CAZ-AVI use as well as the management of patients with infections caused by CAZ-AVI-resistant strains.
OBJECTIVES:Ceftazidime/avibactam (CAZ-AVI), approved in 2015, is an important first-line option for Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC-E). Although still uncommon, resistance to CAZ-AVI has emerged and may represent a serious cause of concern. METHODS: We performed a systematic literature review of clinical and microbiological features of infections and colonisations by CAZ-AVI-resistant KPC-E, focused on the in vivo emergence of CAZ-AVI resistance in different clinical scenarios. RESULTS: Twenty-three papers were retrieved accounting for 42 patients and 57 isolates, mostly belonging to K. pneumoniae ST258 harbouring D179Y substitution in the KPC enzyme. The USA, Greece and Italy accounted for 80% of cases. In one-third of isolates resistance was not associated with previous CAZ-AVI exposure. Moreover, 20% of the strains were colistin-resistant and 80% were extended-spectrum β-lactamase (ESBL)-producers. The majority of infectedpatients had severe underlying diseases (39% cancer, 22% solid-organ transplantation) and 37% died. The abdomen, lung and blood were the most involved infection sites. Infections by CAZ-AVI-resistant strains were mainly treated with combination therapy (85% of cases), with meropenem being the most common (65%) followed by tigecycline (30%), gentamicin (25%), colistin (25%) and fosfomycin (10%). Despite the emergence of resistance, 35% of patients received CAZ-AVI. CONCLUSION: Taken together, these data highlight the need for prompt susceptibility testing including CAZ-AVI for Enterobacterales, at least in critical areas. Resistance to CAZ-AVI is an urgent issue to monitor in order to improve both empirical and targeted CAZ-AVI use as well as the management of patients with infections caused by CAZ-AVI-resistant strains.
Authors: Gabriel Mendes; João F Ramalho; Ana Bruschy-Fonseca; Luís Lito; Aida Duarte; José Melo-Cristino; Cátia Caneiras Journal: Antibiotics (Basel) Date: 2022-01-27