Demographic characteristics of the population
A total of 142 consecutive hospitalised cancer participants with clinical diagnosis of sepsis were recruited into the study, with females 76 (53.5%) and paediatric patients 86 (60.6%) being the majority. The age ranged between 1 – 85 years, with an overall median age 10 (interquartile range [IQR]: 5 – 24) years and a median in-patient hospital stay of 7 (IQR: 4 – 15) days before diagnosis of sepsis was suspected. One hundred and ten (77.5%) participants had haematological neoplasms which comprised mostly of leukaemias and lymphomas whilst 32 (22.5%) had solid tumours such as Wilms tumour, rhabdomyosarcoma and hepatocellular carcinoma. Neutropenia, one of the major sepsis risk factors, was assessed from the patients’ absolute neutrophil counts. The absolute neutrophil count of patients on blood culture sample collection ranged between 20 – 102 700 cells/µl. Neutropenia (< 1000 cells/µl) as previously defined in other studies (7,14) was observed in 43 (39.1%) of the participants with haematological neoplasm and one participant with a solid tumour giving a total of 44 (31.0%) neutropenic patients. There was a strong association between having a haematological neoplasm and being neutropenic (Odds Ratio, 19.9; 95%CI 3.0 – 829.2; p-<0.001). Participants’ demographic characteristics are summarised in Table 1.
Blood cultures and pathogens isolated
Of the 142 participants, fifty (35.2%) had positive blood cultures. Thirty-nine of the 110 patients with haematological malignancies had positive blood cultures with a positive isolation rate of 35.5% contributing 78% of the total number of isolates. Gram-positive bacterial pathogens were the predominant 28 (56.0%) of the causative agents of sepsis in this population with coagulase negative Staphylococcus spp. (CoNS) being the majority contributing 22.0% of the pathogens isolated. E. coli was the second most abundant 8 (16.0%) species isolated. Candida albicans was the only fungal pathogen isolated from one participant with sepsis in this study. Table 2 summarises our findings.
Exposure to antimicrobials and antimicrobial susceptibility profiles
One hundred and twenty-nine 129(90.8%) of our participants were exposed to at least one antimicrobial agent at least 48-hours prior to blood culture collection. The most commonly prescribed antibiotic was ceftriaxone 100/129 (77.5%) followed by gentamicin 75/129 (58.1%) and ciprofloxacin 33 (25.6%). Twenty-seven (20.9%) participants were on fluconazole therapy. At least 3 antibiotics had been administered to 58.0% of the participants prior to blood culture collection.
After performing AST on the isolates, Staphylococci spp. had the highest resistance to penicillin 14 (93.7%), with methicillin resistance observed in 10 (66.7%) of the Staphylococci isolates. Based on CLSI 2017 guideline, the same results can be applied to cloxacillin, augmentin and cefazolin. However, all the isolates were fully susceptible to vancomycin and linezolid.
Among the Gram-negative bacterial isolates, antibiotics such as levofloxacin (52.4%), cefepime (61.9%), cefoxitin (66.7%), piperacillin-tazobactam (71.9%), amikacin (85.7%) and meropenem (95.2%) exhibited moderate to high potency against all Gram-negative isolates. Ampicillin and trimethoprim-sulfamethoxazole were least effective with only 4.8% of the isolates being sensitive. High level of resistance was observed among K. pneumoniae followed by E. coli isolates. Among K. pneumoniae isolates, resistance was observed in ampicillin (100%), trimethoprim-sulfamethoxazole (85.7%) and third generation cephalosporins (71.4%) respectively. Resistance to gentamicin, one of the first line empiric antimicrobial in our setting, was 57.1% among K. pneumoniae isolates. Against third generation cephalosporins that is ceftriaxone, an empiric antimicrobial in the local Essential Medicines List and Standard Treatment Guidelines for Zimbabwe (EDLIZ), and ceftazidime, resistance was observed in 71.4% of these isolates. However, isolates were fully sensitive to amikacin and meropenem and moderately sensitive to cefoxitin (85.7%). E. coli isolates were also fully susceptible to meropenem and amikacin while 75.0% of the isolates were resistant to ceftriaxone, ceftazidime, gentamicin, ciprofloxacin and levofloxacin (see table 4). Trimethoprim-sulfamethoxazole and ampicillin displayed the least activity against E. coli isolates with sensitivities of 0.0% and 12.5% respectively. Other isolates were few to make inferences as they were only a single isolate of each species. These included Serratia odorifera, Acinetobacter species, Salmonella enteritidis, Enterobacter intermedium and Hafnia alvei. Of note, the S. odorifera was only sensitive to levofloxacin and resistant to meropenem and ertapenem. Overall, the proportions of isolates resistant to empiric antimicrobial agents in Zimbabwe (gentamicin and ceftriaxone) among Enterobacteria species were 61.9% and 71.4 respectively.
When we investigated the Enterococcus species, the isolates were fully susceptible to linezolid and vancomycin, while they showed high resistance to tetracycline 2 (20.0%) and ciprofloxacin 4 (40.0%). E. gallinarum was resistant to the majority of drugs with the two isolates being sensitive to vancomycin and linezolid. Streptococcus species on the other hand were all resistant (66.7%) to tetracycline, ampicillin and penicillin. One Streptococcus species, which was identified as Streptococcus bovis, showed resistance to vancomycin. Overall, 69.2% isolates of Enterococcus and Streptococcus species were susceptible to the empiric antimicrobial agents, high dose gentamicin and penicillin.
Finally, a single isolate of C. albicans was the only fungal pathogen isolated from the blood cultures. It proved to be resistant to terbinafine, itraconazole and fluconazole. However, the isolate was sensitive to other antifungals such as micafungin, caspofungin, voriconazole, ketoconazole, miconazole, amphotericin B and flucytosine. Tables 3 to 5 summarises the antimicrobial susceptibility patterns of all the isolates.
Incidence of ESBL production among E. coli and K. pneumoniae isolates
Fifteen isolates of both E. coli and K. pneumoniae obtained in this study were screened for ESBL enzyme production and 10 (66.7%) were phenotypically confirmed to be ESBL producers. E. coli isolates were the main ESBL producers with 6/8 (75.0%). Four (57.1%) of the total K. pneumoniae isolates were also confirmed ESBL producers.