The Threat of Carbapenem-Resistant Gram-Negative Bacteria in Patients with Hematological Malignancies: Unignorable Respiratory Non-Fermentative Bacteria-Derived Bloodstream Infections

Abstract

Background Carbapenem-resistant Gram-negative bacteria (CRGNB) bloodstream infection (BSI) pose a significant threat to the prognosis of hematologic malignancies (HM) patients. Understanding the distribution of pathogenic bacteria, changes in carbapenem-resistant trends, risk factors for CRGNB infections, and exploring the early detection measures can help reduce mortality. Methods We conducted a multicenter retrospective study of Gram-negative bacteria (GNB) BSI in patients with HM in three university-affiliated hospitals in Hunan Province, China, from January 2010 to December 2020. Demographic and clinical data were collected from the hospital electronic medical records system. Results CRGNB caused 138 (15.3%) of 902 GNB BSI. The detection rate of CRGNB increased from 6.4% in 2010–2012 to 35.4% in 2019–2020. The 7-day mortality rate was significantly higher in patients with CRGNB BSI than in patients with carbapenem-susceptible Gram-negative bacteria (CSGNB) BSI [31.9% (44/138) vs 9.7% (74/764), P < 0.001], and the mortality rate in patients with carbapenem-resistant non-fermenting bacteria (CRNFB) bloodstream infections was generally higher than that of carbapenem-resistant Enterobacteriaceae (CRE). Urinary catheter (OR, 2.814; CI=1.395–5.680; P=0.004) and prior exposure to carbapenem (OR, 4.372; CI=2.881–6.635; P<0.001) were independent risk factors for CRGNB BSI. Analysis of co-infections showed that 50%–85% of patients with CRGNB BSI had pulmonary infections, sputum culture results suggested that sputum culture positivity rate was as high as 57.1%–66.7% in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) and Stenotrophomonas maltophilia BSI, and the results of antimicrobial susceptibility testing of sputum cultures were consistent with the blood cultures. Conclusion Carbapenem resistance has dramatically increased in HM patients with GNB BSI in recent years and is associated with a worse outcome, especially for non-fermenting bacteria. In high-risk patients, early screening of the respiratory tract specimens may help to detect CRNFB colonization and protect patients from breakthrough BSI.

Impact of Infection Patterns on the Outcomes of Patients with Hematological Malignancies in Southwest China: A 10-Year Retrospective Case-Control Study

“… 37 It was deduced that our result of irrelevance between sources of infection and in-hospital mortality was more convincing for precluding selection bias, as the aforementioned prospective study was limited to carbapenem-resistant Klebsiella pneumoniae , the most frequent but hard to treat causative pathogen in hospital-acquired pneumonia. However, it should be noted that multi-drug resistant bacteria has been linked to poor outcomes of patients with HM, especially carbapenem-resistant Gram negative bacteria, 38 , 39 despite that our study failed to record the antimicrobial susceptibility phenotypes of bacteria strains due to the limited resources.…”

Upraising Stenotrophomonas maltophilia in Critically Ill Patients: A New Enemy?

“…This was not very prevalent in our study, since only 40% of the studied population had recent exposure to carbapenems. Carbapenem resistance has dramatically increased in hemato-oncology patients with gram negative bacilli BSI in recent years and is associated with a worse outcome, especially for non-fermenting bacteria including Acinetobacter and Stenotrophomonas [ 35 ]. In a real-world, multicenter, retrospective case-control study from five centers in the southeast United States assessing 325 patients, S. maltophilia non-susceptibility had a prevalence of ∼50% to at least one first-line or commonly used agent [ 36 ].…”

“…At the same time, analysis of co-infections showed that 50%–85% of patients with carbapenem-resistant gram-negative bacilli bloodstream infections (BSI) had also pulmonary infections. Sputum culture results suggested that sputum culture positivity rate was as high as 57.1%–66.7% in patients with carbapenem-resistant A.baumannii and S. maltophilia BSI [ 35 ]. The latter underlies the need for infections control bundle implementation against HAP/VAP [ 38 ], but also the need for early screening of the respiratory tract specimens, in order to timely detect multidrug-resistant pathogen colonization and protect patients from breakthrough BSI.…”

Current viewpoint on the epidemiology of nonfermenting Gram-negative bacterial strains

“…In patients receiving chemotherapy for haematological malignancy, S. maltophilia along with A. baumannii contributed independently towards the 30-day mortality during BSIs, surpassing common pathogens, such as Enterobacterales [63]. Moreover, in a retrospective Chinese study of BSIs in patients with hematologic malignancies, the early (7-day) mortality of NFGNB was higher than Enterobacterales (22.6% vs. 9.7%, P < 0.001, respectively), while another Chinese study on BSIs by carbapenem-resistant Gram-negative bacteria, also in patients with hematologic malignancy, had similar results regarding early mortality [64,65]. Finally, another NFGNB associated with infections and increased mortality in haematological malignancies is B. cepacia, with the respiratory tract as the most frequent site of infection [66 ▪ ].…”