Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

The Occurrence of Vibrio species in the Gut of Sardinella madrensis in Port Harcourt, Nigeria

The occurrence of vibrio bacteria in the gut of “Songu”: Sardinella madrensis was investigated using enrichment procedures. Seventy percent (70%) of the total fish samples examined were positive for vibrios. The mean bacterial counts ranged between 2.68 x 102 to 1.30 x 104 cfu/g in all the fish samples. The weight of fish samples ranged between 25.0g and 30.9g and the bacterial counts increased with fish weight. Four major species were isolated, though in varying frequencies and they included Vibrio cholerae (2.7%), V. hollisae (5.4%), V. parahaemolyticus (10.8) and V. vulnificus (81.5%). The presence of these bacterial species in the fish samples might expose the consumers to a wide variety of disease conditions. Keywords: Vibrio flora, “Songu”: Sardinella madrensis, gut Journal of Medical Laboratory Science Vol. 13 (2) 2004: pp. 62-6

Effects of Gasoline on Blood Cells and Liver Functions of Albino Rats (Rattus rattus)

The acute toxicological effects of gasoline on blood cells, and liver functions of albino rats were investigated. The rats were intraperitoneally injected with gasoline at different dose levels and were observed within 24 hours for signs and symptoms of toxicity. From the pilot study, 35.0g/kg was obtained as the minimum dose of gasoline that caused 100% death (LD100). Furthermore, LD50 study gave 12.30g/kg as the dose of gasoline that caused 50% death in rats (median lethal dose). The symptoms observed included occurrence of pallor, sedation, respiratory distress, coma and death and they were dose-dependent. Death rate increased with increase in the concentration of gasoline. The results of the hematological parameters obtained showed decrease in the mean + SEM values with increase in doses of gasoline injection. The biochemical parameters obtained showed an increase in the ALT and AST levels from 0.00 to 35.0g/kg and a corresponding increase in the ALP level from 0.00 to 35.0g/kg, indicating a case of hepatotoxicity. Direct and total bilirubin were also increased with increase in the doses of gasoline. The results, of this study showed that exposure to gasoline is potentially toxic and the degree of toxicity may be influenced by the dose or concentration to which persons are exposed. Keywords: Albino Rat, Gasoline, Histopathology Journal of Medical Laboratory Science Vol. 13 (2) 2004: pp. 24-2

Changes in Immunohaematological Characteristics of Human Immunodeficiency

Highly active anti-retroviral therapy (HAART) has changed the mode of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) care in the developed countries, but its benefits and effects have not been well elucidated in Nigeria. In this case-control study, we have investigated the immediate effects of HAART with stavudine, lamivudine and nevirapine on the haematological and immunological parameters of 70 antiretroviral naïve, HIV-positive subjects during the first 8 weeks of therapy. Thirty HIV-positive antiretroviral naïve individuals not yet on HAART were included as controls. At baseline, treated subjects and controls did not differ significantly in their haematological and immunological parameters. After 8 weeks of HAART, the differences in mean haemoglobin (t = 5.77,

Case Report Kidney Transplant in a 26-Year-Old Nigerian Patient with Sickle Cell Nephropathy

Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD). It has variable presentation, ranging from hyposthenuria to end-stage renal disease (ESRD). Management of ESRD in SCD patients is froth with multiple challenges which has potential to impact negatively the outcome of the patient. Kidney transplant is the preferred renal replacement therapy in these patients. The objective of this case study is to report kidney transplant in a Nigerian young man with sickle cell nephropathy and to highlight the outcome and the challenges to kidney transplant in this patient. The index case is a 26-years-old sickle cell disease patient with ESRD complicated with cardiovascular, pulmonary, immunological, and infective challenges. These conditions were controlled, and the patient had a successful live-related kidney transplant. Kidney transplant is a viable option for sickle cell disease patients with ESRD

Increased incidences of Salmonella, Plasmodium falciparum and hepatitis C viral specific circulating immune complexes in participants from malaria endemic and HIV prevalent area of Nigeria

The present study used dissociated circulating immune complexes (CIC) to identity the burden of exposure to certain infectious agents. The participants were divided into HIV seropositive group (n=100) and HIV seronegative group (n=100). Polyethylene glycol (PEG) 6000 and phosphate buffer techniques were used for precipitation and dissociation of CIC in sera. The dissociated CIC were tested for Salmonella typhi antibody, Plasmodium falciparum histidine rich protein (Pf-hrp)-2 antigen and HCV antibody using commercially available kits. Result showed that Salmonella typhi antibody was detected in 76 (76%) of the HIV seropositive participants; Plasmodium falciparum histidine rich protein-2 (Pf-hrp-2) antigen was detected in 48 (48%) of HIV seropositive participants while Hepatitis C viral antibodies was detected in 20 (20%) of the HIV seropositive participants. Similarly, Salmonella typhi antibody was detected in 24(24%) of the HIV seronegative participants, Pf-hrp-2 antigen was detected in 47(47%) of the participants while Hepatitis C viral antibody was detected in 5(5%) of the HIV seronegative participants. There were significant differences between the number of HIV seropositive and seronegative participants with positive Salmonella typhi (P<0.05) and HCV antibody (P<0.05). The rates of homogeniuty and heterogeniuty of CIC in HIV seropositive participants was; 26 (34%) and 50 (66%) for Salmonella typhi antibody, 3 (6%) and 45 (94%) for Pf-hrp-2 antigen and 0 (0%) and 20 (100%) for HCV antibody, respectively. While the rates of homogeniuty and heterogeniuty of CIC in HIV seronegative participants was 1 (4.2%) and 23 (95.8%) for Salmonella typhi antibody; 25 (53%) and 22 (47%) for Pf-hrp-2 antigen and 3 (60%) and 2 (40%) for HCV antibody respectively in all cases. The finding of the present study suggest that HIV infection may enhance susceptibilty to both salmonella typhi and HCV infection but not Plasmodium falciparum. The study thus revealed that Salmonella and HCV infections may constitute the major secondary infection in HIV infected patients and could be a cause for concern as HIV progressed to AIDS