Research Article: High prevalence of extended-spectrum beta-lactamase-producing Gram-negative pathogens from patients attending Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Amhara region

Date Published: April 15, 2019

Publisher: Public Library of Science

Author(s): Feleke Moges, Setegn Eshetie, Wondwossen Abebe, Feleke Mekonnen, Mulat Dagnew, Abyot Endale, Azanaw Amare, Tigist Feleke, Mucheye Gizachew, Moges Tiruneh, Patrick Butaye.


Infections caused by extended-spectrum beta-lactamases (ESBL) producing Gram-negative bacteria has emerge as a global threat in clinical practices. The treat is more serious in developing countries due to inappropriate use, poor adherence, use of counterfeit, sub-standard antibiotics and poor infection control practices. Data on ESBL producing Gram-negative bacteria are limited in developing countries including Ethiopia. The aim of this study was therefore, to describe the burden of ESBL producing Gram negative pathogens isolated from patients attending at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Amhara region.

A total of 532 clinical samples of blood, urine, stool, wound, abscess, ear discharge, nasal discharge, cervical discharge and body fluid specimens were aseptically collected and bacteriologically processed. Identification of the bacterial species was performed using an automated system (Vitek-2 Compact 27530, USA) and antibiotic susceptibility test was determined by disk diffusion method and selection of antibiotics were in accordance with CLSI guidelines. The MDR pattern of the Gram-negative pathogens was assessed using phenotypic methods of ESBL and carbapenemase production following standard procedure.

A total of 532 samples were processed and 263 pathogens were isolated. Of these, 185 (70.3%) were Gram-negative and 78 (29.7%) Gram-positive. Of the Gram-negative bacteria the high proportion of the isolates were identified from blood 146/185 (78.9%) and 29/185 (15.7%) were from urine cultures. The most common isolate in all clinical samples was Klebsiella pneumoniae 97/185 (52.4%) followed by Escherichia coli 23/185 (12.4%), Acinetobacter baumannii 15/185 (17.6%) and Enterobacter aerogenes 12/185(6.5%). Of the total Gram negatives, the prevalence of MDR was 148/185 (80.0%). Of the MDR isolates the prevalence of ESBL producers were, 127/148 (85.8%) and 24/148 (16.2%) were carbapenemase producers.

Prevalence of MDR and ESBL producing Gram-negative pathogens in this hospital is alarmingly high. Therefore, continuous monitoring of the problem with effective infection prevention and careful selection of empirical therapy are warranted in the study area.

Partial Text

Antibiotics play a critical role in reducing the burden of communicable diseases all over the world. Among the many classes of antibiotics, the β-lactam antibiotics are the most commonly used because of their broad-spectrum activities and better safety profiles [1]. However, emergence of antibiotic resistance threatens the effectiveness of successful treatment of infections and is a public health issue with national and global dimensions. The problem is more alarming in developing countries, where there is high burden of infectious diseases, lack of surveillance networks, laboratory capacity, and appropriate diagnostics [2,3]. Recent advances in drug resistance revealed that emergence of extended spectrum β-lactamase producing Enterobacteriaceae are increasing from time to time. Gram-negative bacilli like Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. are important pathogens and may cause blood stream, abdominal and urinary tract infections. A few studies in Africa reported high case-fatality rate associated with blood stream infection, mainly caused by Gram-negative bacteria, and being 2-fold higher than that of malaria (43.5% versus 20.2%) [4, 5].

Ethical approval was obtained from the institutional review board of the University of Gondar with reference number O/VIP/RCS/05/478/2015. Informed written consent was obtained from each study participants. Children less than 18 years who are not able to give consent were also asked an assent and/or written consent taken from their parents or guardians.

Of the 532 study participants enrolled in the present study, 290 (54.5%) were male, 263 (49.4%) were children aged less than 6 years and only 8 (1.5%) were greater than 60 years. Three hundred and nine (58.9%) were rural dwellers and 459 (86.3%) were inpatients. As most of the study participants came from rural areas, 99 (18.6%) of the study participants were illiterate. Regarding to patient setting majority of the patients were admitted patients, 459 (86.3%). (Table 1).

Half of the clinical samples processed in our study were culture positive of which the Gram- negative pathogens were in the ratio of 3.3:1 compared with the Gram-positive isolates. This is similar to a study done in Iran that the ratio of Gram-negative to Gram-positive bacteria was 3.2:1 [10]. As pointed out by Abe [11], the reason may be because Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia as a result C-reactive protein and IL-6 levels are significantly higher in Gram-negative bacteremia than in Gram-positive bacteremia. These observations suggest a distinct immuno-pathophysiologic behavior of sepsis in patients with Gram-negative bacteremia that may influence clinical outcomes.

The overall MDR isolates in the present study was 80%. Among phenotypically tested Gram-negative bacteria 85.8% were ESBL producers and 16.2% were carbapenemase producers. The Gram negatives showed high level of drug resistance towards the tested cephalosporin except cefoxitin. Although there is an increasing intermediate resistance in cefoxitin and ciprofloxacin, compared to other antibiotics tested; these antibiotics holds promise as an alternative choice of therapy for Gram-negative bacterial infections. Finding high rate of ESBL production in Gram-negative bacteria require strict infection control measures and careful selection of empirical therapy in the study area.