key: cord-0269113-6zjlnrew authors: Mwansa, T. N.; Mulemena, J. A.; Kamvuma, k.; Phiri, C. N.; Chanda, W. title: Antibiotic susceptibility patterns of pathogens isolated from laboratory specimens at Livingstone Central Hospital in Zambia date: 2022-05-20 journal: nan DOI: 10.1101/2022.05.19.22275336 sha: a00a127ea249070c15e26b072838b93e0247ab2e doc_id: 269113 cord_uid: 6zjlnrew Background. Antibiotics are essential commodities in managing bacterial infections in humans, animals and plants but are hampered by the development of antibiotic resistance which is one of the most serious public health threats of the twenty-first century. Moreover, the rate at which novel antibiotics are discovered is slower that the rate of emerging antibiotic resistance. Therefore, the few remaining potent antibiotics in clinical setting should be safeguarded by closer monitoring of their effectiveness via periodic antibiogram studies. This study aimed to evaluate the antibiotic susceptibility patterns of routinely isolated bacteria at Livingstone Central Hospital (LCH). Methods. A cohort retrospective study with secondary information collected from electronic laboratory system generated reports on all isolated organisms at LCH microbiology laboratory for three years (January 2019 to December 2021) was used. Study variables such as age, gender, patients location, name of the organism and the antibiotic susceptibility were considered. Descriptive statistics was used to describe our data and a chi-square test was used for categorical variables where a p-value of <=0.05 was considered as statistically significant. Results . A total of 765 specimens were processed from January 2019 to December 2021 and only 500 (65.4%) met the inclusion criteria for this study. Of the 500, 291(58.2%) specimens were received from female and from the age-group 17-39 years (253, 50.6%) and 40-80 years (145, 29%) in form of blood (331, 66.2%), urine (165, 33%) and sputum (4, 0.8%). The out-patient department (323, 64.6%) had a higher number of specimen culture requests that reduced from 175 (35%) for the year 2019 and 2020 to 150 (30%) for year 2021. Amongst the common bacterial isolates identified, Staphylococcus aureus (142, 28.4%) was the commonest isolate followed by Escherichia coli (91, 18.2%), Enterobacter agglomerans (76, 15.2%), and Klebsiella pneumoniae (43, 8.6%). The resistance pattern indicated that ampicillin (93%) was the least effective drug followed by oxacillin (88%), penicillin (85.6%), co-trimoxazole (81.5%), erythromycin (71.9%), nalidixic acid (68%), ceftazidime (60%), tetracycline (55.1%), and ciprofloxacin (45.9%) whereas the most effective antibiotics were imipenem (14.5%), piperacillin/tazobactam (16.7%) and clindamycin (34.5%). The resistance levels were affected by patient gender, location, and specimen type. However, the screening of methicillin resistant Staphylococcus aureus (MRSA) with cefoxitin showed 76.3% (29/38) susceptibility and 23.7% (9/38) resistance. Conclusion . The commonest bacterial isolates were Staphylococcus aureus, Escherichia coli, Enterobacter agglomerans, Klebsiella pneumoniae and Klebsiella oxytoca. The least effective antibiotics were ampicillin, penicillin, oxacillin, cotrimoxazole, and erythromycin whereas the most effective antibiotics were imipenem, piperacillin/tazobactam, and clindamycin. Therefore, re-establishing of the empiric therapy is needed for proper patient management, studies to determine the levels of extended spectrum beta lactamase- and carbapenemase- producing bacteria are warranted. Antibiotics are essential commodities in managing bacterial infections in humans and 60 animals. However, the spread of antibiotic-resistant bacteria had been increased by the 61 overuse and misuse of antibiotics as well as social and economic factors (1). Therefore, 62 antibiotic resistance is a public health concern that has been recognized globally. 63 Studies have indicated that a lot of lives are lost due to antimicrobial resistance related . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) 64 illnesses every year, and almost 100% β-lactams and some 3rd generation 65 cephalosporins and carbapenems have recorded resistance by some organisms (2) . 66 Prior to the development of the first β-lactam (penicillin) and its release in medical 67 practice, emergence of resistance had been reported and the first β-lactamase enzyme 68 was identified in Escherichia coli (3) . Extended Spectrum β-lactamases (ESBLs) are 69 enzymes that deactivate a variety of β-lactam antibiotics including penicillins, 70 cephalosporins (3rd and 4th generations) and monobactams but less likely to 71 deactivate cephamycins like cefoxitin (3) (4) (5) . Furthermore, the production of 72 carbapenemase enzymes by some Enterobacteriaceae is alarming as these enzymes can 73 break down antibiotics including carbapenem antibiotics, which are typically reserved 74 to treat multidrug-resistant bacterial infections (6). Carbapenem-resistant 75 Enterobacteriaceae (CRE) causes very hard to treat infections because of being resistant 76 to carbapenems that are used on multidrug resistant strains (7). It is sufficed to note 77 that the more bacteria get exposed to antimicrobial agents the more resistance 78 develops. Therefore, there is need to preserve the current antimicrobial agents by using 79 them judiciously otherwise, we risk having pandemic AMR infections that will devastate 80 the global community. 81 In Africa, especially in low and medium-income countries (LMIC), antimicrobial 82 resistance monitoring is inadequate, but the extensive usage of antibiotics to prevent 83 and treat infectious diseases has led to the emergence and spread of antibiotic 84 resistance which has influenced a particular force on susceptible bacteria leading to 85 resistant strain survival, consequently increasing medical costs, illnesses and deaths of 86 patients (8). Therefore, antibiogram studies in LMIC are important to closely monitor 87 the trends of AMR at hospital and national levels. This retrospective study aimed to . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Eligibility criteria. This study included all specimens having information on the 100 patient's gender, age, location (ward/clinic), name of organism and antibiotic 101 susceptibility testing. However, any isolated organism without a species name, and with 102 unknown source (i.e., lack of age-, location-, and gender of patient, and sample type) 103 were excluded from the study. Data collection and analysis. Data from electronic laboratory system generated 105 reports on all isolated organisms at LCH microbiology laboratory for three years 106 (January 2019 to December 2021) was used from which information such as age, 107 gender, patient's location, name of the organism and the antibiotic susceptibility were 108 considered. The collected data was entered, assorted, and coded using Microsoft Excel 109 2019 and then exported to Statistical Package for Social Science (SPSS) version 20 for 110 analysis. Descriptive statistics was used to describe our data. Graph prism 5 was used . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 for graph generation. A chi-square test was used for categorical variables and a p-value 112 of ≤0.05 was considered statistically significant. Ethical consideration. This is a retrospective study that analysed secondary data 114 generated from routine laboratory specimens from both adult and paediatric 115 departments. There was no human interaction, and no personal identifiers were 116 included in this study. However, ethical waiver was granted by Mulungushi University Staphylococcus aureus (142, 28.4%) was the commonest isolate followed by Escherichia . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The association of patient gender, age group, location, and year of isolation with 158 resistant pattern of bacteria isolates. 159 We conducted a chi-square test to determine the link between resistance pattern of 160 bacteria and independent variables. We found that the potency of both nitrofurantoin 161 and cefuroxime were affected by gender. Specifically, the effectiveness of nitrofurantoin (Table 1 ). Further analysis revealed that the Enterobacter aerogenes resistance to co-168 trimoxazole (p=0.005) varied with year of isolation, and so was Staphylococcus aureus 169 resistance to tetracycline (p=0.009), chloramphenicol (p=0.002) and co-trimoxazole . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 20, 2022. Klebsiella oxytoca (4, 3.9%; Fig. 3B ). Antibiotic susceptibility testing was conducted with 187 a panel of antibiotics that are commonly used at LCH. The resistance pattern revealed 188 that ampicillin (95.5%) was the least effective drug followed by oxacillin (87.5%), . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 20, 2022. However, Staphylococcus aureus resistance to chloramphenicol had a significant 239 reduction from 2019 to 2021 (p=0.006) whereas its resistance to penicillin was the 240 highest in 0-16years age group (p=0.012, Table 2 ). is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 20, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 Generally, our study revealed that blood specimens were the most frequently processed 261 specimen with 66.2% followed by urine (33%) and sputum (0.8%) indicating 262 bacteraemia and urinary tract infections as the commonly managed infections at LCH. A . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 20, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 similar study conducted in Ndola, Zambia found urine and blood specimens as the 264 common processed specimens at Ndola Teaching Hospital (12). Furthermore, many 265 specimens came from out-patient department (64.7%), and we further noted that the 266 influx of specimens to the laboratory reduced from 35% (for 2019 and 2020) to 30% 267 (for 2021), conceivably because of the COVID19 pandemic that caused Government to 268 put the country on periodic lockdown, thereby reducing the number of patients that 269 accessed health services. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 20, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 288 Several studies reveal that sepsis due to bacterial infections emanates from urinary 289 tract infections which are more prevalent in women (17) (18) (19) . So, we expected to observe producing ESBLs, whereas piperacillin/tazobactam is the combination of a fourth 308 generation, extended-spectrum penicillin and a beta-lactamase inhibitor that is also 309 effective against β-lactamase producing penicillin-resistant bacterial species (24, 25) . Due to the wide spread of antibiotic resistance resulting from ESBL producing 311 Enterobacteriaceae, carbapenems should normally be reserved as alternative treatment 312 for such infections (26) but our study found that both imipenem and . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 20, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 Characterization of bacterial pathogens from paediatric department. Antimicrobial resistance impacts all population and the increasing trend of drug Characterization of bacterial isolates from in-patient department 345 Hospital acquired infections (HAIs) are of major safety concern for both health care 346 providers and the patients (31). These infections are usually acquired after 347 hospitalization and manifest 48-72 hours after admission to the hospital. Even though it 348 was difficult to determine whether the infections were hospital-acquired or not, due to 349 the retrospective nature of our study, we thought of having a glimpse on the resistant 350 levels of bacteria isolated from IPD. We noticed that more blood and urine specimens 351 came from female patients. The most isolated bacterium was Staphylococcus aureus 352 (28.2%), followed by Escherichia coli (18.1%), Enterobacter agglomerans (14.7%), Klebsiella pneumoniae (6.8%), CoNS (4.5%), and Klebsiella oxytoca (4.5%). The study 354 revealed that ampicillin (93.4%) was the least effective drug followed by penicillin 355 (83%), co-trimoxazole (82.5%), oxacillin (80%), erythromycin (74.4%), nalidixic acid 356 (70.7%), cefuroxime (60%), and tetracycline (48.5%) whereas the most effective 357 antibiotics were norfloxacin (18.2%), imipenem (18.5%) and clindamycin (28.6%). The 358 picture of multidrug resistant strains was observed amongst IPD specimens and this 359 calls for an in-depth analysis of antibiotic susceptibility patterns of nosocomial 360 pathogens. The prevalence of gram-negative HAI-and carbapenem resistant-pathogens . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 20, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 have been reported across the globe (32, 33) and the cases are steadily increasing, 362 posing a risk on the cost and effective management of HAIs. Therefore, antimicrobial 363 stewardship programs (27, 31) should be implemented in referral hospitals in Zambia 364 and beyond. In conclusion, our study has revealed the importance of periodic monitoring of 366 antibiotic resistance patterns in hospitals. The study discovered Staphylococcus aureus, 367 Escherichia coli, Enterobacter agglomerans and Klebsiella pneumoniae as frequently 368 isolated bacteria from blood and urine specimens with highly resistance to ampicillin, 369 penicillin, oxacillin, co-trimoxazole, and erythromycin but imipenem was the most 370 effective antibiotic. Similarly, paediatric and IPD isolated strains presented with 371 multidrug resistance to commonly used antibiotics at LCH. Therefore, more studies to 372 establish the prevalence of ESBL-and carbapenemase-producing bacteria for empiric 373 therapy redesigning are warranted as monitoring data on antimicrobial susceptibility of 374 common bacterial organisms is crucial for decision-making and quick detection of AMR 375 at hospital levels. 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