Prevalence of multidrug-resistant Gram-negative pathogens isolated from febrile neutropenic cancer patients with bloodstream infections in Egypt and new synergistic antibiotic combinations

Abstract

IntroductionBloodstream infections with multidrug-resistant (MDR) Gram-negative bacteria (GNB) are among the most frequent complications in immunocompromised cancer patients because of their considerable morbidity and mortality. Several guidelines on antimicrobial therapy have addressed empirical treatment for such serious infections; however, the emergence of microbial resistance has become a significant problem worldwide.Materials and methodsIn this study, starting from November 2015 to October 2016, a total of 529 blood specimens were collected from febrile neutropenic cancer patients at a tertiary care cancer hospital in Egypt.ResultsOn examination for positive bacterial growth, it was found that 334 specimens showed no growth, while 195 were positive. Out of the 195 positive culture specimens, 102 (102/195, 52.3%) were Gram-negative and 93 (93/195, 47.7%) were Gram-positive. Out of the 102 GNB, 70 (70/102, 68.6%) were MDR, including Escherichia coli (27/70, 38.6%), Klebsiella pneumoniae (24/70, 34.3%), Acinetobacter baumannii (9/70, 12.8%), Enterobacter cloacae (4/70, 5.7%), Pseudomonas aeruginosa (2/70, 2.8%), Klebsiella oxytoca (2/70, 2.8%), and Klebsiella ornithinolytica (2/70, 2.8%). All MDR GNB showed high resistance to ampicillin, cefepime, ceftriaxone, and cephradine (minimum inhibitory concentration at which 50% of the isolates were inhibited [MIC50] >512 μg/mL for each). However, they showed good susceptibility to colistin (MIC50 <1 μg/mL). The most common extended-spectrum β-lactamases (ESBLs) genes detected were ctx-m (39/70, 55.7%), shv (31/70, 44.3%), and tem (22/70, 31.4%). The most common aminoglycoside-resistant gene detected was aac(6′)-Ib (42/70, 60%) followed by the plasmid-mediated quinolone resistance determinants; qnrA (2/70, 2.8%), qnrB (9/70, 12.8%), and qnrS (19/70, 27.1%). ESBL determinants were significantly associated with resistance to ciprofloxacin, levofloxacin, amikacin, and carbapenems (P-value <0.005). The fractional inhibitory concentration index for ampicillin/sulbactam plus ceftriaxone, ampicillin/sulbactam plus amikacin, and amikacin plus levofloxacin showed synergism against 29 (29/70, 41.4%), 19 (19/70, 27.1%), and 11 (11/70, 15.7%) isolates of the tested MDR GNB isolates, respectively.ConclusionAccordingly, new empirical antibiotics should be administered including the use of colistin or meropenem alone or both against the MDR GNB in neutropenic cancer patients.

The Role of Gut Microbiome Perturbation in Fatigue Induced by Repeated Stress from Chemoradiotherapy: A Proof of Concept Study

“…E. coli and Salmonella commonly proliferate in the blood cultures of hospitalized cancer patients with fever [31]. Some strains of E. coli particularly in immunocompromised cancer patients have been linked to potentially severe and life-threatening infections such as UTI [32], both acute and chronic diarrhea (e.g., Enteropathogenic and enterohaemorrhagic E. coli diarrhea [33], or bloodstream infections) [34]. For example, one study (using real-time PCR to quantify bacteria) observed that the microflora composition of the majority of patients experiencing chemotherapy-induced diarrhea showed increase in E. coli and a decrease in Lactobacillus spp.…”

<p>Carbapenemase Producers Among Extensive Drug-Resistant Gram-Negative Pathogens Recovered from Febrile Neutrophilic Patients in Egypt</p>

“…Accordingly, out of the 342 GNB; 188 (54.9%) isolates were MDR which is in accordance with previous studies and imposes weak infection control strategies. 26 , 27 Despite the fact that the antibiogram analysis of recovered GNB is raising concerns, yet, the overall sensitivity patterns of amikacin, doxycycline and tigecycline ranging from 70% to 85% rise as a promising hope.…”

The relationship between mortality and microbiological parameters in febrile neutropenic patients with hematological malignancies

“…Nowadays, the development of intensive chemotherapy protocols and interventional procedures have resulted a serious increase in cure rates of the patients, while immunosuppression caused by these treatments also enhances incidence rates of infection. 1 , 2 The relationship between fever and infection in neutropenic patients was defined during the 1960s. Initially, this rarely encountered relationship was described as a serious clinical entity after more widespread and intensive use of cytotoxic drugs and its treatment was started thanks to developed guidelines.…”

“…The body temperature of ≥38.3°C was measured once from the oral or axillary route or body temperature of 38.0-38.2°C persisting for one hour was defined as neutropenic fever. 1 - 4 Since pathogenic agents are frequently of endogenous origin and polymicrobial in neutropenic patients, foci or agents of infection cannot be identified. 7 , 8 …”