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      Treatment outcomes, antibiotic use and its resistance pattern among neonatal sepsis patients attending Bahawal Victoria Hospital, Pakistan

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          Abstract

          Background

          Sepsis is one of the major causes of neonatal mortality in Pakistan. This study aimed to investigate the treatment outcomes, antibiotic use and its resistance pattern among neonatal sepsis patients attending a tertiary care hospital in Pakistan. We also aimed to identify the factors affecting mortality in neonatal sepsis patients.

          Methods

          A descriptive, cross-sectional study was conducted in the pediatric wards of the Bahawal Victoria Hospital, Bahawalpur, Pakistan. All eligible neonatal sepsis patients who were registered at the study site from January 1, 2019 to June 30, 2019 were included in the study. The data collection form included information on patient’s characteristics, antibiotic use and its sensitivity pattern, laboratory and microbiological data, and final treatment outcomes. Treatment outcomes included, discharged (with treatment success), leave against medical advice (LAMA), discharged on request (DOR) and death. Multivariable binary logistic regression analysis was used to find the independent factors associated with death. A p-value of less than 0.05 was considered statistically significant.

          Results

          Among the total 586 patients, 398 (67.9%) were male, 328 (56%) were preterm, 415 (70.8%) were diagnosed with early onset sepsis, 299 (51%) were born with low birth weight. Most of the patients (n = 484, 82.6%) were treated with amikacin+cefotaxime at the start of treatment. Culture was positive in 52 (8.9%) patients and the most commonly identified bacteria included, Klebsiella species (n = 19, 36.5%) followed by E. coli (n = 15, 28.5%) and Staphylococcus aureus (n = 8, 15.4%). The identified bacterial isolates showed high level of resistance against the antibiotics initiated at the start of the treatment, while resistance against piperacillin+tazobactam, imipenem, vancomycin and linezolid was very low. Just under half of the patients (n = 280, 47.8%) successfully completed the treatment (i.e., discharged with treatment success), while 123 (21%) patients died during treatment. In multivariable binary logistic regression, the factors which still remained significantly associated with neonatal death included, preterm delivery (AOR 9.59; 95% CI 4.41, 20.84), sub-optimal birth weight (AOR 5.13; 95% CI 2.19, 12.04), early onset sepsis (AOR 2.99; 95% CI 1.39, 6.41) and length of hospital stay (AOR 0.76; 95% CI 0.67, 0.88).

          Conclusion

          The mortality rate associated with sepsis was high in our study cohort. The bacterial isolates showed high level of resistance against the antibiotics started as the empiric therapy. Rational use of antibiotics can decrease the adverse outcomes in neonatal sepsis patients.

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          Most cited references55

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          Every Newborn: progress, priorities, and potential beyond survival.

          In this Series paper, we review trends since the 2005 Lancet Series on Neonatal Survival to inform acceleration of progress for newborn health post-2015. On the basis of multicountry analyses and multi-stakeholder consultations, we propose national targets for 2035 of no more than 10 stillbirths per 1000 total births, and no more than 10 neonatal deaths per 1000 livebirths, compatible with the under-5 mortality targets of no more than 20 per 1000 livebirths. We also give targets for 2030. Reduction of neonatal mortality has been slower than that for maternal and child (1-59 months) mortality, slowest in the highest burden countries, especially in Africa, and reduction is even slower for stillbirth rates. Birth is the time of highest risk, when more than 40% of maternal deaths (total about 290,000) and stillbirths or neonatal deaths (5·5 million) occur every year. These deaths happen rapidly, needing a rapid response by health-care workers. The 2·9 million annual neonatal deaths worldwide are attributable to three main causes: infections (0·6 million), intrapartum conditions (0·7 million), and preterm birth complications (1·0 million). Boys have a higher biological risk of neonatal death, but girls often have a higher social risk. Small size at birth--due to preterm birth or small-for-gestational-age (SGA), or both--is the biggest risk factor for more than 80% of neonatal deaths and increases risk of post-neonatal mortality, growth failure, and adult-onset non-communicable diseases. South Asia has the highest SGA rates and sub-Saharan Africa has the highest preterm birth rates. Babies who are term SGA low birthweight (10·4 million in these regions) are at risk of stunting and adult-onset metabolic conditions. 15 million preterm births, especially of those younger than 32 weeks' gestation, are at the highest risk of neonatal death, with ongoing post-neonatal mortality risk, and important risk of long-term neurodevelopmental impairment, stunting, and non-communicable conditions. 4 million neonates annually have other life-threatening or disabling conditions including intrapartum-related brain injury, severe bacterial infections, or pathological jaundice. Half of the world's newborn babies do not get a birth certificate, and most neonatal deaths and almost all stillbirths have no death certificate. To count deaths is crucial to change them. Failure to improve birth outcomes by 2035 will result in an estimated 116 million deaths, 99 million survivors with disability or lost development potential, and millions of adults at increased risk of non-communicable diseases after low birthweight. In the post-2015 era, improvements in child survival, development, and human capital depend on ensuring a healthy start for every newborn baby--the citizens and workforce of the future. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Neonatal sepsis.

            Neonatal sepsis is the cause of substantial morbidity and mortality. Precise estimates of neonatal sepsis burden vary by setting. Differing estimates of disease burden have been reported from high-income countries compared with reports from low-income and middle-income countries. The clinical manifestations range from subclinical infection to severe manifestations of focal or systemic disease. The source of the pathogen might be attributed to an in-utero infection, acquisition from maternal flora, or postnatal acquisition from the hospital or community. The timing of exposure, inoculum size, immune status of the infant, and virulence of the causative agent influence the clinical expression of neonatal sepsis. Immunological immaturity of the neonate might result in an impaired response to infectious agents. This is especially evident in premature infants whose prolonged stays in hospital and need for invasive procedures place them at increased risk for hospital-acquired infections. Clinically, there is often little difference between sepsis that is caused by an identified pathogen and sepsis that is caused by an unknown pathogen. Culture-independent diagnostics, the use of sepsis prediction scores, judicious antimicrobial use, and the development of preventive measures including maternal vaccines are ongoing efforts designed to reduce the burden of neonatal sepsis.
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              Access to effective antimicrobials: a worldwide challenge.

              Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: ValidationRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 January 2021
                2021
                : 16
                : 1
                : e0244866
                Affiliations
                [1 ] Department of Pharmacy Practice, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Punjab, Pakistan
                [2 ] Department of Pharmacy Practice, Faculty of Pharmacy and Health Sciences, University of Balochistan, Quetta, Balochistan, Pakistan
                [3 ] Department of Pulmonology, Bahawal Victoria Hospital, Bahawalpur, Punjab, Pakistan
                Nitte University, INDIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-6866-8152
                https://orcid.org/0000-0001-8029-7163
                Article
                PONE-D-20-09960
                10.1371/journal.pone.0244866
                7806133
                33439876
                45cf8258-4bb0-4e3b-bdcb-164bcec622d0
                © 2021 Atif et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 April 2020
                : 17 December 2020
                Page count
                Figures: 1, Tables: 7, Pages: 16
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Sepsis
                Neonatal Sepsis
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobial Resistance
                Antibiotic Resistance
                Medicine and Health Sciences
                Pharmacology
                Antimicrobial Resistance
                Antibiotic Resistance
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Birth Weight
                Biology and Life Sciences
                Developmental Biology
                Neonates
                Medicine and Health Sciences
                Pediatrics
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Death Rates
                Biology and Life Sciences
                Microbiology
                Bacteriology
                Gram Negative Bacteria
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information Files.

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                Uncategorized

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