Mechanisms of Bacterial Drug Resistance with Special Emphasis on Phenotypic and Molecular Characterization of Extended Spectrum Beta-lactamase.

Antibiotics are designed to effectively treat bacterial infections while minimizing harm to the human body. They work by targeting specific components of bacteria or by disrupting essential processes such as cell wall synthesis, membrane function, protein production, and metabolic pathways. However, the misuse and overuse of antibiotics have led to the emergence of drug resistance in humans, animals, and agriculture, contributing to the global spread of this problem. Drug resistance can be either innate or acquired, with acquired resistance involving changes in the bacterial chromosomes or transferable elements. Bacterial species employ various mechanisms of drug resistance, including modifying the antibiotic targets, inactivating the drug, reducing uptake or increasing efflux, overexpressing the target, utilizing alternative pathways, and forming biofilms. One significant concern in the realm of drug resistance revolves around the emergence and proliferation of extended-spectrum beta-lactamases (ESBLs), a gene that is found in most gram-negative bacteria, primarily carried by Escherichia coli and Klebsiella pneumoniae in healthcare settings. ESBL-mediated resistance poses challenges for diagnosis, treatment, infection control, and antibiotic stewardship. Accurate detection of ESBL genes is crucial, and phenotypic methods are commonly used for initial screening. However, these methods have limitations, and confirmatory molecular techniques such as PCR and DNA sequencing are employed to accurately identify ESBL genes. Despite the significant global concerns surrounding ESBLs, they have spread worldwide, mainly facilitated by healthcare settings, inappropriate antimicrobial use, and host susceptibility. Addressing this issue requires implementing comprehensive measures, including enhanced surveillance, strict infection control practices, antibiotic stewardship programs, rapid diagnostic methods, alternative therapies, public education initiatives, and research focused on developing new drugs. Furthermore, collaboration among the healthcare, public health, and research sectors is pivotal in effectively combating the escalating threat posed by ESBL-mediated resistance. Antibiotics have revolutionized medical care by effectively treating bacterial infections. However, the emergence of ESBL gene resistance poses a global challenge that requires an integrated approach to prevent a threatening future.

A Prospective Study of Causes of Illness and Death in Preterm Infants in Ethiopia: The SIP Study Protocol.

BACKGROUND: With nearly 15 million annual preterm births globally, preterm birth is the most common cause of neonatal death. Forty to 60 % of neonatal deaths are directly or indirectly associated with preterm mortality. As countries aim to meet the Sustainable Development Goals to reduce neonatal mortality, significant reductions in preterm mortality are needed. This study aims to identify the common causes of preterm illness and their contribution to preterm mortality in low-resource settings. This article will describe the methods used to undertake the study. METHODS: This is a prospective, multi-centre, descriptive clinical study. Socio-demographic, obstetric, and maternal factors, and clinical and laboratory findings will be documented. The major causes of preterm mortality will be identified using clinical, laboratory, imaging, and autopsy methods and use the national Ethiopian guidelines on management of preterm infants including required investigations to reach final diagnoses. The study will document the clinical and management protocols followed in these settings. The approach consists of clinical examinations and monitoring, laboratory investigations, and determination of primary and contributory causes of mortality through both clinical means and by post-mortem examinations. An independent panel of experts will validate the primary and contributory causes of mortality. To obtain the estimated sample size of 5000 preterm births, the study will be undertaken in five hospitals in three regions of Ethiopia, which are geographically distributed across the country. All preterm infants who are either born or transferred to these hospitals will be eligible for the study. Three methods (last menstrual period, physical examination using the New Ballard Score, and ultrasound) will be used to determine gestational age. All clinical procedures will be conducted per hospital protocol and informed consent will be taken from parents or caretakers prior to their participation in the study as well as for autopsy if the infant dies. DISCUSSION: This study will determine the major causes of death and illness among hospitalized preterm infants in a low-resource setting. The result will inform policy makers and implementers of areas that can be prioritized in order to contribute to a significant reduction in neonatal mortality.

Hierarchical Predictors of Mortality in Neonatal Sepsis at Jimma Medical Center, Ethiopia: A Case-Control Study.

Background: Neonatal sepsis made the neonatal period the most perilous time for child survival, and it continued to cause preventable mortalities worldwide. These mortalities stem from the interaction of several factors that have not been sufficiently studied and, in some cases, remain overlooked. Thus, the study aims to investigate the predictors of mortality that arise from the interaction of these factors and quantitatively determine their etiologic fraction. Methods: A case-control study with hierarchical data input was conducted at Jimma Medical Center (JMC) in Oromia, Ethiopia, spanning from May 2022 to July 2023. It employed logistic regression to calculate adjusted odds ratios (AORs) and their corresponding 95% confidence intervals (CI) at a significance level of p ≤ 0.05. The model adjusted odds ratios (ORs) for variables within each level and farther levels and presented an etiologic fraction (EF), indicating the proportion of neonatal mortality attributable to specific factors. Results: The analysis of 67 cases and 268 controls unveiled significant predictors of mortality in sepsis that emerged from distal, intermediate, and proximal levels. In the final model, thus, rural residence [AOR 3.1; 95% CI (1.5, 6.3), p ≤ 0.01], prolonged labor [AOR 4.5; 95% CI (2.2, 9.3), p ≤ 0.01], prematurity [AOR 3.9; 95% CI (1.9, 7.9), P ≤ 0.0], gram-negative bacteremia [AOR 3.8; 95% CI (1.9, 7.6); P ≤ 0.01], convulsion [AOR 3.2; 95% CI (1.6, 6.4); P ≤ 0.03], low birth weight [AOR 2.7; 95% CI (1.3, 5.4); P≤0.01], and delayed breastfeeding [AOR 2.5; 95% CI (1.2, 4.9); P ≤ 0.01] attributed a variable percentage of mortality. Conclusion: Factors emerging and interacting at distal (residence), intermediate (prolonged labor), and proximal (prematurity, birth weight, convulsion, bacterial etiology, and feeding) levels influence neonatal mortality in sepsis at JMC. Therefore, concurrently improving rural family characteristics, managing labor duration, strengthening diagnostic stewardship, and promoting essential newborn care can actively prevent and reduce these mortalities.

Neonatal Sepsis Due to Multidrug-resistant Bacteria at a Tertiary Teaching Hospital in Ethiopia.

BACKGROUND: The burden of multidrug-resistant bacterial infections in low-income countries is alarming. This study aimed to identify the bacterial etiologies and antibiotic resistance patterns among neonates in Jimma, Ethiopia. METHODS: An observational longitudinal study was conducted among 238 presumptive neonatal sepsis cases tested with blood and/or cerebrospinal fluid culture. The bacterial etiologies were confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrometry. The antibiotic resistance patterns were determined using the automated disc diffusion method (Bio-Rad) and the results were interpreted based on the European Committee on Antimicrobial Susceptibility Testing 2021 breakpoints. Extended-spectrum ß-lactamases were detected using a double disc synergy test and confirmed by Mast discs (Mast Diagnostica GmbH). RESULTS: A total of 152 pathogens were identified. Of these, Staphylococcus aureus (18.4%) was the predominant isolate followed by Klebsiella pneumoniae (15.1%) and Escherichia coli (10.5%). All the isolates exhibited a high rate of resistance to first- and second-line antibiotics ranging from 73.3% for gentamicin to 93.3% for ampicillin. Furthermore, 74.4% of the Gram-negative isolates were extended-spectrum ß-lactamase producers and 57.1% of S. aureus strains were methicillin resistant. The case fatality rate was 10.1% and 66.7% of the deaths were attributable to infections by multidrug-resistant pathogens. CONCLUSIONS: The study revealed a high rate of infections with multidrug-resistant pathogens. This poses a significant challenge to the current global and national target to reduce neonatal mortality rates. To address these challenges, it is important to employ robust infection prevention practices and continuous antibiotic resistance testing to allow targeted therapy.

Epidemiologic features of neonatal sepsis and its COVID-19 associated temporal patterns in Jimma Medical Center, Ethiopia: A Joinpoint regression analysis.

BACKGROUND: Neonatal sepsis remains a leading cause of morbidity and mortality in neonates across all regions, including Africa. Compared to developed and some developing countries, there are relatively few epidemiological trends for neonatal sepsis and associated patterns with COVID-19 in Ethiopia. We modeled an epidemiological trend and pattern to aid in the monitoring of changes in neonatal sepsis. METHODS: Retrospective data were collected from all admissions to the Neonatal Intensive Care Unit (NICU) in Ethiopia at Jimma Medical Center between May 2019 and April 2022. We analyzed the monthly neonatal sepsis incidence, mortality, and case-fatality rates using STATA software. Finally, we modeled a monthly time series of neonatal sepsis incidence trends and patterns associated with the COVID-19-impacted period using Joinpoint software. For all analyses, a P value of 0.05 was considered statistically significant at the 95% confidence interval (CI). RESULTS: In the 36 months, 6796 cases were admitted to the NICU, with a 9.5% (95% CI: 9.1, 10.0) incidence rate of neonatal sepsis. The overall admission mortality rate was 16.5% (95% CI: 13.6, 19.8), while sepsis-attributed mortality was 7.1% (95% CI: 5.8, 8.5). The data showed an unstable decreasing trend for three Joinpoints (August 2020, December 2020, and August 2021). Notably, a decrease in the incidence trend was observed from May 2019 to August 2020 (MPC, -4.1; 95% CI: -7.6, -0.5; P = 0.03), followed by a sharp increase (MPC, 23.7; 95% CI: -13.8, 77.7; P = 0.24) from August 2020 to December 2020. From December 2020 to August 2021, there was again a decreasing trend (MPC, -13.8; 95% CI: -23.3, -3.5; P = 0.01), followed by a slight increase from August 2021 to April 2022 (MPC, 4.2; 95% CI: -8.4, 18.6; P = 0.52). Finally, the study revealed an association between patterns of neonatal sepsis incidence trends and COVID-19, with a Joinpoint jump model comparability ratio (CR = 0.43) between pre- and COVID-19-impacted periods. CONCLUSIONS: Neonatal sepsis was prevalent at Jimma Medical Center, but it was on an unstably declining trend. The current results suggest a potential temporal association between the intensity of COVID-19 containment measures and a change in the incidence trend and patterns of neonatal sepsis. However, the quantified contribution of a particular containment measure requires further investigation.

A cross-sectional study design to assess the sexual experiences and contraceptive use of adolescents and youths attending high school and college in Jimma town.

BACKGROUND: Adolescents and youths in Ethiopia have limited access to reproductive health services designed to address their needs. Therefore, the study aims to assess adolescents' and youth's sexual practice, contraceptive use, and behavioral patterns towards safe sexual exercise. METHODS: A quantitative cross-sectional study design was used on 374 students selected from high school and vocational colleges to assess their sexual experience and contraceptive use and related perceptions using pre-tested self-administered semi-structured questionnaires. We used descriptive analyses to report their sexual and reproductive health status and logistic regression to examine the association between contraceptive use and other variables. RESULTS: The results show that 52.7% of the respondents (students) migrated or moved from rural to urban to continue their high school and college education at urban. 41.7% of the respondents were with less than 18 years, of which 75.9% of them already initiated sexual intercourse. Of all the students who started sexual intercourse (51.1%), only 30.9% used contraceptives, but condom use accounts for 49.2%. Overall, 84.8% of those who practiced sexual intercourse were at risk of acquiring sexually transmitted diseases due to not using a condom. About 3% of the respondents reported unwanted pregnancy experiences, of which 64% of these pregnancies were reported to be aborted. CONCLUSION: Adolescents and youths attending high schools and College are at increased risk of acquiring HIV and unwanted pregnancy due to low levels of contraceptive use. Specifically, a designed youths-friendly reproductive health service is needed to avert related problems and contribute to sustainable development goals.

Cystic echinococcosis, a food-borne zoonotic neglected tropical disease in slaughtered cattle at Jimma Town municipal abattoir, Southwest Ethiopia.

Cystic echinococcosis (CE), also called hydatid disease (HD) is a parasitic disease caused by larval stage of Echinococcus granulosus and is considered as a food-borne zoonotic, neglected tropical disease (NTD). Backyard slaughtering and inadequate veterinary services are major risk factors for high prevalence of the disease in developing countries. Here, we determined the prevalence of HD in the cattle slaughtered in the municipal abattoir of Jimma Town, Southwest Ethiopia by an abattoir based cross-sectional study, which included 389 randomly selected cattle. The source of cattle, age, sex, breed, the body condition and any acute illness were assessed in ante-mortem investigations. Moreover, during post-mortem examination, vital organs suspected for hydatid cysts (HCs) were carefully examined by close inspection, digital palpation and sharp incision. Fertility and viability were tested for all HCs containing hydatid fluid. The overall prevalence of HC among the cattle was 52.9% (206/389). Lungs were the most affected organ 70.9% (146/206), and 29.6%, 62.1%, and 8.7% of the HCs were fertile, sterile and calcified, respectively. The HC abundance and viability had statistically significant association with the organs affected, and fertile HCs were most common at lung. Collectively, our study revealed that CE is highly prevalent in slaughtered cattle at the Jimma area, Ethiopia and lungs are the major affected organs. An integrated prevention and control strategies from various sectors through 'One Health' approach are essential to tackle the problem, and proper awareness must be built up among people about the devastating effects of the disease.

Major causes of death in preterm infants in selected hospitals in Ethiopia (SIP): a prospective, cross-sectional, observational study.

BACKGROUND: Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia. METHODS: We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data. FINDINGS: Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 [45%]); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 [30%]), and asphyxia (151 [14%]). Hypothermia was the most common contributory cause of preterm mortality (770 [69%]). The highest mortality occurred in infants younger than 28 weeks of gestation (89 [86%] of 104), followed by infants aged 28-31 weeks (512 [54%] of 952), 32-34 weeks (349 [18%] of 1975), and 35-36 weeks (159 [8%] of 1888). INTERPRETATION: Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death. FUNDING: Bill & Melinda Gates Foundation.

Efficacy and Safety of a Single-Dose Mebendazole 500 mg Chewable, Rapidly-Disintegrating Tablet for Ascaris lumbricoides and Trichuris trichiura Infection Treatment in Pediatric Patients: A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study.

This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of a new chewable, rapidly-disintegrating mebendazole (MBZ) 500 mg tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment. Pediatric patients (1-15 years; N = 295; from Ethiopia and Rwanda) excreting A. lumbricoides and/or T. trichiura eggs were enrolled. The study had a screening phase (3 days), a double-blind treatment phase (DBP, 19 days), and an open-label phase (OLP, 7 days). Patients received MBZ or placebo on day 1 of DBP and open-label MBZ on day 19 ± 2 after stool sample collection. Cure rates (primary endpoint), defined as species-specific egg count of 0 at the end of DBP, were significantly higher in the MBZ group than placebo for A. lumbricoides (83.7% [72/86; 95% CI: 74.2%; 90.8%] versus 11.1% [9/81; 95% CI: 5.2%; 20.1%], P < 0.001) and for T. trichiura (33.9% [42/124; 95% CI: 25.6%; 42.9%] versus 7.6% [9/119; 95% CI: 3.5%; 13.9%], P < 0.001). Egg reduction rates (secondary endpoint) were significantly higher in the MBZ group than placebo for A. lumbricoides (97.9% [95% CI: 94.4; 99.9] versus 19.2% [95% CI: -5.9; 41.5]; P < 0.001) and T. trichiura (59.7% [95% CI: 33.9; 78.8] versus 10.5% [95% CI: -16.8; 32.9]; P = 0.003). Treatment-emergent adverse events (TEAEs) in MBZ group occurred in 6.3% (9/144) of patients during DBP and 2.5% (7/278) during OLP. No deaths, serious TEAEs, or TEAEs leading to discontinuations were reported. A 500 mg chewable MBZ tablet was more efficacious than placebo for the treatment of A. lumbricoides and T. trichiura infections in pediatric patients, and no safety concerns were identified.

Prevalence and intensity of soil-transmitted helminth infections among pre-school age children in 12 kindergartens in Jimma Town, southwest Ethiopia.

BACKGROUND: Pre-school age children (preSAC) remain difficult to reach in mass drug administration (MDA) programmes to control soil-transmitted helminth (STH) infections. Kindergartens provide a unique platform to increase the coverage of MDA in preSAC in Ethiopia, but surveys assessing STHs among preSAC in kindergartens are scarce. METHODS: We report the prevalence and intensity of STH infections among 622 preSAC in 12 kindergartens in Jimma, Ethiopia. RESULTS: STHs were found in all kindergartens, with prevalence exceeding 50% in 8 kindergartens. The majority of the infections were of low intensity. CONCLUSIONS: This study highlights the importance of kindergartens as an additional opportunity for MDA in Ethiopia.