Bloodstream infection caused by extensively drug-resistant Acinetobacter baumannii in cancer patients: high mortality associated with delayed treatment rather than with the degree of neutropenia

Abstract

This study aimed to describe severe infections with extensively drug-resistant Acinetobacter baumannii-calcoaceticus complex (XDR-ABC), as well as to investigate risk factors for mortality, in cancer patients. It was a retrospective study including all patients diagnosed with XDR-ABC bacteraemia during hospitalization in the intensive care unit of a cancer hospital between July 2009 and July 2013. Surveillance cultures were collected weekly during the study period, and clonality was analysed using pulsed field gel electrophoresis (PFGE). We analysed underlying diseases, oncology therapy, neutrophil counts, infection site and management of infection, in terms of their correlation with 30-day mortality. During the study period, 92 patients with XDR-ABC bacteraemia were identified, of whom 35 (38.0%) were patients with haematological malignancy. We identified XDR-ABC strains with four different profile patterns, 91.3% of patients harbouring the predominant PFGE type. Of the 92 patients with XDR-ABC bacteraemia, 66 (71.7%) had central line-associated bloodstream infections; infection occurred during neutropenia in 22 (23.9%); and 58 (63.0%) died before receiving the appropriate therapy. All patients were treated with polymyxin, which was used in combination therapy in 30 of them (32.4%). The 30-day mortality rate was 83.7%. Multivariate analysis revealed that septic shock at diagnosis of XDR-ABC infection was a risk factor for 30-day mortality; protective factors were receiving appropriate therapy and invasive device removal within the first 48 h. Among cancer patients, ineffective management of such infection increases the risk of death, more so than do features such as neutropenia and infection at the tumour site.

Risk Factors, Clinical Presentation, and Outcome of Acinetobacter baumannii Bacteremia

“…Previous studies have demonstrated that crude mortality rates in patients with AB bacteremia varied between 30 and 76%, and factors associated with worse prognosis include immunosuppression (Gulen et al, 2015; Townsend et al, 2015; Gu et al, 2016), drug resistance (Lee et al, 2007; Sunenshine et al, 2007; Fu et al, 2015; Guo et al, 2016), severity of underlying illness (Seifert et al, 1995; Chopra et al, 2013, 2014; Nutman et al, 2014), inappropriate antimicrobial therapy (Esterly et al, 2011; Huang et al, 2012; Shorr et al, 2014; Freire et al, 2016), septicemia (Huang et al, 2012; Ñamendys-Silva et al, 2015; Freire et al, 2016), and prior antibiotic exposure (Chopra et al, 2013, 2014; Gu et al, 2016; Liu et al, 2016). …”

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

“…The hallmark of the XDR phenotype is carbapenem resistance. CRAB strains tend to be XDR-that is, resistant to all other antibiotics, with the exception of polymyxins, tigecycline, and sometimes aminoglycosides (50,52,53). NHSN and Eurofins surveillance data highlight that carbapenem resistance occurs in more than 50% of A. baumannii ICU isolates in the United States, by far the highest rate of resistance for any pathogen surveyed (27,181,182).…”

“…To circumvent the intrinsic resistance of many mouse strains to A. baumannii infection, artificial models have been used, such as infecting mice intraperitoneally (a clinically irrelevant route of entry) or mixing the inoculum with porcine mucin as a foreign body that inhibits the host's immune system from rapidly clearing the organism (59,60). In addition, mice are often made neutropenic prior to infection even though neutropenia is not a common risk factor for infections caused by A. baumannii, and the vast majority of patients infected with A. baumannii have neither deficiency in leukocyte numbers nor overt defects in leukocyte function (25,(50)(51)(52)(53)(61)(62)(63)(64)(65)(66)(67)(68). Results from such models must be interpreted circumspectly given the unclear applicability to clinical disease.…”

Changes in the early mortality of adult patients with carbapenem-resistant Acinetobacter baumannii bacteremia during 11 years at an academic medical center

“…In the later period, such patients were less frequent and the number of central line infections was more common. Bacteremic pneumonia is one of the most fatal types of bacterial infection [17], whereas central line infection can be controlled relatively easily with early removal of infected devices [18]. In this study, central line infection was independently associated with 14-day survival.…”