Bloodstream infections in adult patients with malignancy, epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance

Abstract

Background: This study aimed to investigate the epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance bacterial bloodstream infections (BSIs) among adult cancer patients in Shiraz, Iran. We also report a four-year trend of antimicrobial resistance patterns of BSIs.

Methods: We conducted a retrospective study at a referral oncology hospital from July 2015 to August 2019, which included all adults with confirmed BSI.

Results: 2393 blood cultures tested during the four-year study period; 414 positive cultures were included. The mean age of our patients was 47.57 ± 17.46 years old. Central Line-Associated BSI (CLABSI) was more common in solid tumors than patients with hematological malignancies. Gram-negative (GN) bacteria were more detected (63.3%, 262) than gram-positive bacteria (36.7%, 152). Escherichia coli was the most common gram-negative organism (123/262, 47%), followed by Pseudomonas spp. (82/262, 31%) and Klebsiella pneumoniae (38/262, 14.5%). Coagulase-negative staphylococci (CoNS) was the most frequently isolated pathogen among gram-positive bacteria (83/152, 54.6%). Acinetobacter spp., Pseudomonas spp., E. coli, and K. pneumoniae were the most common Extended-Spectrum Beta-Lactamase (ESBL) producers (100, 96.2, 66.7%, and 60.7, respectively). Acinetobacter spp., Pseudomonas spp., Enterobacter spp., E. coli, and K. pneumoniae were the most common carbapenem-resistant (CR) isolates (77.8, 70.7, 33.3, 24.4, and 13.2%, respectively). Out of 257 Enterobacterales and non-fermenter gram-negative BSIs, 39.3% (101/257) were carbapenem-resistant. Although the incidence of multi-drug resistance (MDR) gram-negative BSI increased annually during 2015-2018, the mortality rate of gram-negative BSI remains unchanged at about 20% (p-value = 0.55); however, the mortality rate was significantly greater (35.4%) in those with resistant gram-positive BSI (p-value = 0.001). The overall mortality rate was 21.5%. Early (7-day mortality) and late mortality rate (30-day mortality) were 10 and 3.4%, respectively.

Conclusions: The emergence of MDR gram-negative BSI is a significant healthcare problem in oncology centers. The high proportion of the most frequently isolated pathogens were CR and ESBL-producing Enterobacterales and Pseudomonas spp. We have few effective choices against MDRGN BSI, especially in high-risk cancer patients, which necessitate newer treatment options.

Keywords: Bloodstream infection; Cancer; Carbapenem-resistant isolates; Extended-Spectrum Beta-lactamase producing pathogens; Mortality; Multidrug-resistant gram-negative infection.

Fig. 1

Flow chart of study population screened and enrolled associated with bloodstream infections caused by gram-negative and gram-positive bacteria in patients treated at the Amir oncology hospital between July 2015 to August 2019

Fig. 2

Incidence of febrile neutropenia, bloodstream infections, mortality rate/10000 cases, and hospitalized adults with cancer during 2015–2019. FN: febrile neutropenia episodes; BSI: bloodstream infection

Fig. 3

The percentage frequency distribution of different gram-negative and gram-positive bacteria isolated from blood cultures

Fig. 4

The annual frequency of ESBL and CRE-associated BSI, in addition to MRCoNS, associated BSI (labels represent case numbers). CRGN includes carbapenem resistance Enterobacterales and non-fermenter spp.

Fig. 5

Antimicrobial susceptibility results of 123 E. coli (A) and 81 Pseudomonas spp. (B) isolates recovered from blood cultures during 2015–2019

Fig. 6

Antimicrobial susceptibility results of 38 K. pneumonia (A) and of 80 coagulase-negative staphylococci (CoNS) isolates (B) recovered from blood cultures during 2015–2019

Fig. 7

Comparative analysis for antibiotic resistance rate between E. coli, K. pneumoniae, and Pseudomonas spp. with all gram-negative isolates (A, B, and C, respectively)