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1.
Antibiotics (Basel) ; 12(5)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37237826

RESUMO

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

2.
J Virus Erad ; 9(4): 100355, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38213904

RESUMO

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the WHO African Region (AFRO). This means the full extent of HBV infection is not well described, leading to a lack of investment in diagnostics, treatment and disease prevention. Clinical trials in the WHO AFRO region have been increasing over time and many test for infectious diseases including hepatitis B virus (HBV) to determine baseline eligibility for participants, however these screening data are not reported. Here we review data from six clinical trials completed at the KEMRI-Wellcome Trust Research Programme between 2016 and 2023 that screened for HBV using hepatitis B surface antigen (HBsAg) as part of the trial exclusion criteria. 1727 people had HBsAg results available, of which 60 tested positive. We generated a crude period HBV prevalence estimate of 3.5% (95% CI 2.6-4.5%), and after standardisation for sex and age to account for the population structure of the Kilifi Health Demographics Surveillance System (KHDSS), the prevalence estimate increased to 5.0% (95% CI 3.4-6.6%). The underrepresentation of women in these trials was striking with 1263/1641 (77%) of participants being male. Alanine aminotransferase (ALT) was significantly higher in the HBsAg positive group but was not outside the normal range. We argue that routine collation and publishing of data from clinical trials could increase precision and geographical representation of global HBV prevalence estimates, enabling evidence-based provision of clinical care pathways and public health interventions to support progress towards global elimination targets. We do acknowledge when using clinical trials data for seroprevalence estimates, that local population structure data is necessary to allow standardisation of results, and the point of care tests used here are limited in sensitivity and specificity.

3.
Wellcome Open Res ; 7: 3, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600002

RESUMO

Background: Early onset neonatal sepsis (EONS) typically begins prior to, during or soon after birth and may be rapidly fatal. There is paucity of data on the aetiology of EONS in sub-Saharan Africa due to limited diagnostic capacity in this region, despite the associated significant mortality and long-term neurological impairment. Methods: We compared pathogens detected in cord blood samples between neonates admitted to hospital with possible serious bacterial infection (pSBI) in the first 48 hours of life (cases) and neonates remaining well (controls). Cord blood was systematically collected at Kilifi County Hospital (KCH) from 2011-2016, and later tested for 21 bacterial, viral and protozoal targets using multiplex PCR via TaqMan Array Cards (TAC). Results: Among 603 cases (101 [17%] of whom died), 179 (30%) tested positive for ≥1 target and 37 (6.1%) tested positive for multiple targets. Klebsiella oxytoca, Escherichia coli/Shigella spp., Pseudomonas aeruginosa, and Streptococcus pyogenes were commonest. Among 300 controls, 79 (26%) tested positive for ≥1 target, 11 (3.7%) were positive for multiple targets, and K. oxytoca and P. aeruginosa were most common. Cumulative odds ratios across controls: cases (survived): cases (died) were E. coli/Shigella spp. 2.6 (95%CI 1.6-4.4); E. faecalis 4.0 (95%CI 1.1-15); S. agalactiae 4.5 (95%CI 1.6-13); Ureaplasma spp. 2.9 (95%CI 1.3-6.4); Enterovirus 9.1 (95%CI 2.3-37); and Plasmodium spp. 2.9 (95%CI 1.4-6.2). Excluding K. oxytoca and P. aeruginosa as likely contaminants, aetiology was attributed in 9.4% (95%CI 5.1-13) cases using TAC. Leading pathogen attributions by TAC were E. coli/Shigella spp. (3.5% (95%CI 1.7-5.3)) and Ureaplasma spp. (1.7% (95%CI 0.5-3.0)). Conclusions: Cord blood sample may be useful in describing EONS pathogens at birth, but more specific tests are needed for individual diagnosis. Careful sampling of cord blood using aseptic techniques is crucial to minimize contamination. In addition to culturable bacteria, Ureaplasma and Enterovirus were causes of EONS.

4.
Front Immunol ; 13: 971866, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203568

RESUMO

Shigella is associated with a significant burden of disease worldwide among individuals of all ages and is the major cause of moderate and severe diarrhea in children under five years of age in low- and middle-income countries. Several candidate vaccines against Shigella species are currently under clinical development. The investigational 1790GAHB vaccine against Shigella sonnei is based on GMMA (Generalized Modules for Membrane Antigens) technology. The vaccine was well tolerated and induced high antibody levels in early-phase clinical trials in both Shigella-endemic and non-endemic settings. The present analysis assessed the bactericidal activity of antibodies induced by 1790GAHB in healthy Kenyan adults during a phase 2a, controlled, randomized study (NCT02676895). Participants received two doses of 1790GAHB 4 weeks apart containing either 1.5/25 µg or 6/100 µg O antigen/protein, or active comparator vaccines (Control). Serum bactericidal activity (SBA) against S. sonnei was assessed at pre-vaccination (D1), 28 days post-first dose (D29) and 28 days post-second dose (D57), using a luminescence-based assay. Most participants had SBA titers above the lower limit of quantification of the assay at D1. SBA geometric mean titers increased 3.4-fold in the 1.5/25 µg group and 6.3-fold in the 6/100 µg group by D29 and were maintained at D57. There was no increase in SBA geometric mean titers in the Control group. A strong correlation was observed between SBA titers and anti-S. sonnei lipopolysaccharide serum immunoglobulin G antibody concentrations (Pearson correlation coefficient = 0.918), indicating that SBA can effectively complement enzyme-linked immunosorbent assay data by indicating the functionality of 1790GAHB-induced antibodies.


Assuntos
Disenteria Bacilar , Shigella , Vacinas , Adulto , Anticorpos Antibacterianos , Criança , Pré-Escolar , Disenteria Bacilar/prevenção & controle , Humanos , Imunoglobulina G , Quênia , Lipopolissacarídeos , Metilmetacrilatos , Antígenos O , Shigella sonnei
6.
Arch Dis Child ; 107(9): 802-810, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35078765

RESUMO

OBJECTIVE: To assess pharmacokinetics and changes to sodium levels in addition to adverse events (AEs) associated with fosfomycin among neonates with clinical sepsis. DESIGN: A single-centre open-label randomised controlled trial. SETTING: Kilifi County Hospital, Kenya. PATIENTS: 120 neonates aged ≤28 days admitted being treated with standard-of-care (SOC) antibiotics for sepsis: ampicillin and gentamicin between March 2018 and February 2019. INTERVENTION: We randomly assigned half the participants to receive additional intravenous then oral fosfomycin at 100 mg/kg two times per day for up to 7 days (SOC-F) and followed up for 28 days. MAIN OUTCOMES AND MEASURES: Serum sodium, AEs and fosfomycin pharmacokinetics. RESULTS: 61 and 59 infants aged 0-23 days were assigned to SOC-F and SOC, respectively. There was no evidence of impact of fosfomycin on serum sodium or gastrointestinal side effects. We observed 35 AEs among 25 SOC-F participants and 50 AEs among 34 SOC participants during 1560 and 1565 infant-days observation, respectively (2.2 vs 3.2 events/100 infant-days; incidence rate difference -0.95 events/100 infant-days (95% CI -2.1 to 0.20)). Four SOC-F and 3 SOC participants died. From 238 pharmacokinetic samples, modelling suggests an intravenous dose of 150 mg/kg two times per day is required for pharmacodynamic target attainment in most children, reduced to 100 mg/kg two times per day in neonates aged <7 days or weighing <1500 g. CONCLUSION AND RELEVANCE: Fosfomycin offers potential as an affordable regimen with a simple dosing schedule for neonatal sepsis. Further research on its safety is needed in larger cohorts of hospitalised neonates, including very preterm neonates or those critically ill. Resistance suppression would only be achieved for the most sensitive of organisms so fosfomycin is recommended to be used in combination with another antimicrobial. TRIAL REGISTRATION NUMBER: NCT03453177.


Assuntos
Fosfomicina , Sepse Neonatal , Sepse , Antibacterianos/efeitos adversos , Criança , Fosfomicina/efeitos adversos , Gentamicinas , Humanos , Lactente , Recém-Nascido , Sepse Neonatal/tratamento farmacológico , Sepse/tratamento farmacológico , Sódio/uso terapêutico
7.
BMC Med ; 19(1): 122, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34082778

RESUMO

BACKGROUND: Diagnosing bacterial meningitis is essential to optimise the type and duration of antimicrobial therapy to limit mortality and sequelae. In sub-Saharan Africa, many public hospitals lack laboratory capacity, relying on clinical features to empirically treat or not treat meningitis. We investigated whether clinical features of bacterial meningitis identified prior to the introduction of conjugate vaccines still discriminate meningitis in children aged ≥60 days. METHODS: We conducted a retrospective cohort study to validate seven clinical features identified in 2002 (KCH-2002): bulging fontanel, neck stiffness, cyanosis, seizures outside the febrile convulsion age range, focal seizures, impaired consciousness, or fever without malaria parasitaemia and Integrated Management of Childhood Illness (IMCI) signs: neck stiffness, lethargy, impaired consciousness or seizures, and assessed at admission in discriminating bacterial meningitis after the introduction of conjugate vaccines. Children aged ≥60 days hospitalised between 2012 and 2016 at Kilifi County Hospital were included in this analysis. Meningitis was defined as positive cerebrospinal fluid (CSF) culture, organism observed on CSF microscopy, positive CSF antigen test, leukocytes ≥50/µL, or CSF to blood glucose ratio <0.1. RESULTS: Among 12,837 admissions, 98 (0.8%) had meningitis. The presence of KCH-2002 signs had a sensitivity of 86% (95% CI 77-92) and specificity of 38% (95% CI 37-38). Exclusion of 'fever without malaria parasitaemia' reduced sensitivity to 58% (95% CI 48-68) and increased specificity to 80% (95% CI 79-80). IMCI signs had a sensitivity of 80% (95% CI 70-87) and specificity of 62% (95% CI 61-63). CONCLUSIONS: A lower prevalence of bacterial meningitis and less typical signs than in 2002 meant the lower performance of KCH-2002 signs. Clinicians and policymakers should be aware of the number of lumbar punctures (LPs) or empirical treatments needed for each case of meningitis. Establishing basic capacity for CSF analysis is essential to exclude bacterial meningitis in children with potential signs.


Assuntos
Criança Hospitalizada , Meningites Bacterianas , Criança , Humanos , Lactente , Quênia/epidemiologia , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/epidemiologia , Estudos Retrospectivos , Punção Espinal
10.
Arch Dis Child ; 106(2): 130-136, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32819909

RESUMO

BACKGROUND: Detection of meningitis is essential to optimise the duration and choice of antimicrobial agents to limit mortality and sequelae. In low and middle-income countries most health facilities lack laboratory capacity and rely on clinical features to empirically treat meningitis. OBJECTIVE: We conducted a diagnostic validation study to investigate the performance of clinical features (fever, convulsions, irritability, bulging fontanel and temperature ≥39°C) and WHO-recommended signs (drowsiness, lethargy, unconsciousness, convulsions, bulging fontanel, irritability or a high-pitched cry) in discriminating meningitis in young infants. DESIGN: Retrospective cohort study. SETTING: Kilifi County Hospital. PATIENTS: Infants aged <60 days hospitalised between 2012 and 2016. MAIN OUTCOME MEASURE: Definite meningitis defined as positive cerebrospinal fluid (CSF) culture, microscopy or antigen test, or leucocytes ≥0.05 x 10∧9/L. RESULTS: Of 4809 infants aged <60 days included, 81 (1.7%) had definite meningitis. WHO-recommended signs had sensitivity of 58% (95% CI 47% to 69%) and specificity of 57% (95% CI 56% to 59%) for definite meningitis. Addition of history of fever improved sensitivity to 89% (95% CI 80% to 95%) but reduced specificity to 26% (95% CI 25% to 27%). Presence of ≥1 of 5 previously identified signs had sensitivity of 79% (95% CI 69% to 87%) and specificity of 51% (95% CI 50% to 53%). CONCLUSIONS: Despite a lower prevalence of definite meningitis, the performance of previously identified signs at admission in predicting meningitis was unchanged. Presence of history of fever improves the sensitivity of WHO-recommended signs but loses specificity. Careful evaluation, repeated assessment and capacity for lumbar puncture and CSF microscopy to exclude meningitis in most young infants with potential signs are essential to management in this age group.


Assuntos
Testes Diagnósticos de Rotina/normas , Meningites Bacterianas/diagnóstico , Serviços de Saúde da Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Prevalência , Estudos Retrospectivos , Serviços de Saúde Rural , Sensibilidade e Especificidade
11.
PLoS One ; 12(8): e0182354, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28787002

RESUMO

BACKGROUND: Bloodstream infection is a common cause of morbidity in children aged <5 years in developing countries. In studies reporting bacteremia in Africa, coagulase-negative Staphylococci (CoNS) are commonly isolated. However, it is currently unclear whether children who are highly susceptible to infection because of severe acute malnutrition (SAM) or HIV should be treated with antimicrobials specifically to cover CoNS. We aimed to determine the clinical significance of CoNS amongst children admitted to a rural hospital in Kenya in relation to nutritional and HIV status. METHODS: Systematically collected clinical and microbiological surveillance data from children aged 6-59 months admitted to Kilifi County Hospital (2007-2013) were analysed. Multivariable regression was used to test associations between CoNS isolation from blood cultures and SAM (MUAC <11.5cm or nutritional oedema (kwashiorkor)), and HIV serostatus; and among children with SAM or HIV, associations between CoNS isolation and mortality, duration of hospitalization and clinical features. RESULTS: CoNS were isolated from blood culture in 906/13,315 (6.8%) children, of whom 135/906 (14.9%) had SAM and 54/906 (6.0%) were HIV antibody positive. CoNS isolation was not associated with SAM (MUAC<11.5cm (aOR 1.11, 95% CI 0.88-1.40) or kwashiorkor (aOR 0.84, 95% CI 0.48-1.49)), or a positive HIV antibody test (aOR 1.25, 95% CI 0.92-1.71). Among children with SAM or a positive HIV antibody test, CoNS isolation was not associated with mortality or prolonged hospitalization. CONCLUSION: In a large, systematic study, there was no evidence that antimicrobial therapy should specifically target CoNS amongst children with SAM or HIV-infection or exposure.


Assuntos
Antibacterianos/farmacologia , Infecções por HIV/complicações , Kwashiorkor/complicações , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/enzimologia , Staphylococcus/fisiologia , Antibacterianos/uso terapêutico , Bacteriemia/complicações , Pré-Escolar , Coagulase/metabolismo , Feminino , Humanos , Lactente , Quênia , Masculino , Staphylococcus/efeitos dos fármacos
12.
Pediatr Infect Dis J ; 36(11): 1073-1078, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28731901

RESUMO

BACKGROUND: Neonatal mortality remains high in sub-Saharan Africa, and a third of deaths are estimated to result from infection. While coagulase-negative staphylococci (CoNS) are leading neonatal pathogens in resource-rich settings, their role, and the need for early anti-Staphylococcal treatment in empiric antibiotic guidelines, is unknown in sub-Saharan Africa. METHODS: We examined systematic clinical and microbiologic surveillance data from all neonatal admissions to Kilifi County Hospital (1998-2013) to determine associated case fatality and/or prolonged duration of admission associated with CoNS in neonates treated according to standard World Health Organization guidelines. RESULTS: CoNS was isolated from blood culture in 995 of 9552 (10%) neonates. Case fatality among neonates with CoNS isolated from blood did not differ from other neonatal admissions (P = 0.2), and duration of admission was not prolonged [odds ratio (OR) = 0.9 (0.7-1.0), P = 0.040]. Neonates with CoNS were more likely to have convulsions [OR = 1.4 (1.0-1.8), P = 0.031] but less likely to have impaired consciousness or severe indrawing [OR = 0.8 (0.7-0.9), P = 0.025; OR = 0.9 (0.7-1.0), P = 0.065]. CONCLUSIONS: CoNS isolation in blood cultures at admission was not associated with adverse clinical outcomes in neonates treated according to standard World Health Organization guidelines for hospital care in this setting. There is no evidence that first-line antimicrobial treatment guidelines should be altered to increase cover for CoNS infections in neonates in this setting.


Assuntos
Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Recém-Nascido/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Adolescente , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Hemocultura/estatística & dados numéricos , Criança , Pré-Escolar , Coagulase , Pesquisa Empírica , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/mortalidade , Quênia , Masculino , Estudos Retrospectivos , Infecções Estafilocócicas/epidemiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/enzimologia , Adulto Jovem
13.
Front Immunol ; 8: 1884, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29375556

RESUMO

Shigellosis is a mild-to-severe diarrheal infection, caused by the genus Shigella, and is responsible for significant morbidity and mortality worldwide. We evaluated the safety and immunogenicity of an investigational Shigella sonnei vaccine (1790GAHB) based on generalized modules for membrane antigens (GMMA) in Kenya, a Shigella-endemic country. This phase 2a, observer-blind, controlled randomized study (NCT02676895) enrolled 74 healthy adults aged 18-45 years, of whom 72 were vaccinated. Participants received, in a 1:1:1 ratio, two vaccinations with the 1790GAHB vaccine at doses of either 1.5/25 µg of O antigen (OAg)/protein (group 1.5/25 µg) or 5.9/100 µg (group 5.9/100 µg) at day (D) 1 and D29, or vaccination with a quadrivalent meningococcal vaccine at D1 and tetanus, diphtheria, and acellular pertussis vaccine at D29 (control group). Solicited and unsolicited adverse events (AEs), serious AEs (SAEs), and AEs of special interest (neutropenia and reactive arthritis) were collected. Anti-S. sonnei lipopolysaccharide (LPS) serum immunoglobulin G (IgG) geometric mean concentrations (GMC) were evaluated at D1, D29, and D57 and compared to anti-S. sonnei LPS antibody levels in convalescent patients naturally exposed to S. sonnei. The percentages of participants with seroresponse were also calculated. The most frequently reported solicited local and systemic AEs across all groups were pain and headache, respectively. Only one case of severe systemic reaction was reported (severe headache after first vaccination in group 5.9/100 µg). Seven and three episodes of neutropenia, assessed as probably or possibly related to vaccination respectively, were reported in the investigational and control groups, respectively. No other SAEs were reported. Despite very high baseline anti-S. sonnei LPS serum IgG levels, the 1790GAHB vaccine induced robust antibody responses. At D29, GMC increased 2.10- and 4.43-fold from baseline in groups 1.5/25 and 5.9/100 µg, respectively, whereas no increase was observed in the control group. Antibody titers at D57 were not statistically different from those at D29. Seroresponse was 68% at D29 and 90% at D57 in group 1.5/25 µg, and 96% after each vaccination in group 5.9/100 µg. The 1790GAHB vaccine was well tolerated and highly immunogenic in a population of African adults, regardless of the GMMA OAg/protein content used.

14.
Curr Opin Infect Dis ; 28(3): 225-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25887615

RESUMO

PURPOSE OF REVIEW: This review discusses the rational development of guidelines for the management of neonatal sepsis in developing countries. RECENT FINDINGS: Diagnosis of neonatal sepsis with high specificity remains challenging in developing countries. Aetiology data, particularly from rural, community-based studies, are very limited, but molecular tests to improve diagnostics are being tested in a community-based study in South Asia. Antibiotic susceptibility data are limited, but suggest reducing susceptibility to first-and second-line antibiotics in both hospital and community-acquired neonatal sepsis. Results of clinical trials in South Asia and sub-Saharan Africa assessing feasibility of simplified antibiotic regimens are awaited. SUMMARY: Effective management of neonatal sepsis in developing countries is essential to reduce neonatal mortality and morbidity. Simplified antibiotic regimens are currently being examined in clinical trials, but reduced antimicrobial susceptibility threatens current empiric treatment strategies. Improved clinical and microbiological surveillance is essential, to inform current practice, treatment guidelines, and monitor implementation of policy changes.


Assuntos
Antibacterianos/administração & dosagem , Sepse/tratamento farmacológico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Países em Desenvolvimento/estatística & dados numéricos , Estudos de Viabilidade , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Guias de Prática Clínica como Assunto , Vigilância de Evento Sentinela , Sepse/mortalidade , Resultado do Tratamento
15.
Pediatr Infect Dis J ; 34(6): 659-61, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25806843

RESUMO

Infections are among the leading causes of neonatal mortality, and about 75% of the burden occurs in developing countries. Diagnosis of neonatal sepsis in these countries is dependent on the recognition of a set of nonspecific clinical signs that maximize sensitivity because staff making initial assessments may not have specialist pediatric training. Accurate diagnosis is usually limited by the unavailability of reliable microbiological investigation. The World Health Organization recommends ampicillin (or penicillin; cloxacillin if staphylococcal infection is suspected) plus gentamicin for empiric treatment of neonates with suspected clinical sepsis or meningitis. However, there is a lack of comprehensive data on the causes of infection and antimicrobial susceptibility in developing countries to support these recommendations, especially in rural settings. Bacterial pathogens (predominantly Gram negative) with reduced susceptibility to empiric medication have been reported, with variations both between and within regions. Nosocomial infections with resistant organisms and high case fatality challenge the first-line use of cephalosporins. Improving local surveillance data using standardized antimicrobial susceptibility testing methods and validation of diagnostic algorithms against microbial findings are essential. Standardized reporting of treatment outcomes is required to evaluate practice, provide guidance on second-line regimes and for studies of new approaches, such as simplified community-based regimens, and to determine the appropriate duration of empiric treatment for apparently low-risk neonates with early resolution of clinical signs, or where available, negative blood cultures. Thus, a multifaceted approach, with attention to microbiological quality assurance, is needed to better guide antimicrobial use and reduce mortality and long-term impairments.


Assuntos
Antibacterianos/uso terapêutico , Doenças do Recém-Nascido/tratamento farmacológico , Sepse/tratamento farmacológico , Países em Desenvolvimento , Gentamicinas/uso terapêutico , Humanos , Recém-Nascido , beta-Lactamas/uso terapêutico
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