Prior Antibiotic Therapy and the Onset of Healthcare-Associated Infections Sustained by Multidrug-Resistant <i>Klebsiella pneumoniae</i> in Intensive Care Unit Patients: A Nested Case–Control Study
Giuseppe Migliara,
Valentina Baccolini,
Claudia Isonne,
Sara Cianfanelli,
Carolina Di Paolo,
Annamaria Mele,
Lorenza Lia,
Angelo Nardi,
Carla Salerno,
Susanna Caminada,
Vittoria Cammalleri,
Francesco Alessandri,
Guglielmo Tellan,
Giancarlo Ceccarelli,
Mario Venditti,
Francesco Pugliese,
Carolina Marzuillo,
Corrado De Vito,
Maria De Giusti,
Paolo Villari
Affiliations
Giuseppe Migliara
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Valentina Baccolini
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Claudia Isonne
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Sara Cianfanelli
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Carolina Di Paolo
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Annamaria Mele
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Lorenza Lia
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Angelo Nardi
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Carla Salerno
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Susanna Caminada
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Vittoria Cammalleri
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Francesco Alessandri
Department of Anesthesia and Intensive Care Medicine Azienda, Universitaria-Ospedaliera Policlinico Umberto I, 00185 Rome, Italy
Guglielmo Tellan
Department of Anesthesia and Intensive Care Medicine Azienda, Universitaria-Ospedaliera Policlinico Umberto I, 00185 Rome, Italy
Giancarlo Ceccarelli
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Mario Venditti
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Francesco Pugliese
Department of Anesthesia and Intensive Care Medicine Azienda, Universitaria-Ospedaliera Policlinico Umberto I, 00185 Rome, Italy
Carolina Marzuillo
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Corrado De Vito
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Maria De Giusti
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Paolo Villari
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Epidemiological research has demonstrated direct relationships between antibiotic consumption and the emergence of multidrug-resistant (MDR) bacteria. In this nested case–control study, we assessed whether prior exposure to antibiotic therapy and its duration affect the onset of healthcare-associated infections (HAIs) sustained by MDR Klebsiella pneumoniae (MDR-Kp) in intensive care unit patients. Cases were defined as patients who developed an MDR-Kp HAI. Controls matched on sex and the length of intensive care unit (ICU) stay were randomly selected from the at-risk population. Any antibiotic agent received in systemic administration before the onset of infection was considered as antibiotic exposure. Multivariable conditional logistic regression analyses were performed to estimate the effect of prior exposure to each antibiotic class (Model 1) or its duration (Model 2) on the onset of HAIs sustained by MDR-Kp. Overall, 87 cases and 261 gender-matched controls were compared. In Model 1, aminoglycosides and linezolid independently increased the likelihood of developing an MDR-Kp HAI, whereas exposure to both linezolid and penicillins reduced the effect of linezolid alone. In Model 2, cumulative exposure to aminoglycosides increased the likelihood of the outcome, as well as cumulative exposures to penicillins and colistin, while a previous exposure to both penicillins and colistin reduced the influence of the two antibiotic classes alone. Our study confirms that aminoglycosides, penicillins, linezolid, and colistin may play a role in favoring the infections sustained by MDR-Kp. However, several double exposures in the time window before HAI onset seemed to hinder the selective pressure exerted by individual agents.
