Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza- Tanzania

Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC), Tanzania to determine the prevalence of neonatal sepsis, predictors of positive blood culture, deaths and antimicrobial susceptibility, thus providing essential information to formulate a policy for management of neonatal sepsis. This was a prospective cross sectional study involving 300 neonates admitted at BMC neonatal unit between March and November 2009. Standard data collection form was used to collect all demographic data and clinical characteristics of neonates. Blood culture was done on Brain Heart Infusion broth followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the disc diffusion method. Among 770 neonates admitted during the study period; 300 (38.9%) neonates were diagnosed to have neonatal sepsis by WHO criteria. Of 300 neonates with clinical neonatal sepsis 121(40%) and 179(60%) had early and late onset sepsis respectively. Positive blood culture was found in 57 (47.1%) and 92 (51.4%) among neonates with early and late onset neonatal sepsis respectively (p = 0.466). Predictors of positive blood culture in both early and late onset neonatal sepsis were inability to feed, lethargy, cyanosis, meconium stained liquor, premature rupture of the membrane and convulsion. About 49% of gram negatives isolates were resistant to third generation cephalosporins and 28% of Staphylococcus aureus were found to be Methicillin resistant Staphylococcus aureus (MRSA). Deaths occurred in 57 (19%) of neonates. Factors that predicted deaths were positive blood culture (p = 0.0001), gram negative sepsis (p = 0.0001) and infection with ESBL (p = 0.008) or MRSA (p = 0.008) isolates. Our findings suggest that lethargy, convulsion, inability to feed, cyanosis, PROM and meconium stained liquor are significantly associated with positive blood culture in both early and late onset disease. Mortality and morbidity on neonatal sepsis is high at our setting and is significantly contributed by positive blood culture with multi-resistant gram negative bacteria

Pharmacokinetics and Pharmacodynamics of Antibacterials, Antifungals, and Antivirals Used Most Frequently in Neonates and Infants

Antimicrobials and antivirals are widely used in young infants and neonates. These patients have historically been largely excluded from clinical trials and, as a consequence, the pharmacokinetics and pharmacodynamics of commonly used antibacterials, antifungals, and antivirals are incompletely understood in this population. This review summarizes the current literature specific to neonates and infants regarding pharmacokinetic parameters and changes in neonatal development that affect antimicrobial and antiviral pharmacodynamics. Specific drug classes addressed include aminoglycosides, aminopenicillins, cephalosporins, glycopeptides, azole antifungals, echinocandins, polyenes, and guanosine analogs. Within each drug class, the pharmacodynamics, pharmacokinetics, and clinical implications and future directions for prototypical agents are discussed. β-Lactam antibacterial activity is maximized when the plasma concentration exceeds the minimum inhibitory concentration for a prolonged period, suggesting that more frequent dosing may optimize β-lactam therapy. Aminoglycosides are typically administered at longer intervals with larger doses in order to maximize exposure (i.e., area under the plasma concentration–time curve) with gestational age and weight strongly influencing the pharmacokinetic profile. Nonetheless, safety concerns necessitate therapeutic drug monitoring across the entire neonatal and young infant spectrum. Vancomycin, representing the glycopeptide class of antibacterials, has a long history of clinical utility, yet there is still uncertainty about the optimal pharmacodynamic index in neonates and young infants. The high degree of pharmacokinetic variability in this population makes therapeutic drug monitoring essential to ensure adequate therapeutic exposure. Among neonates treated with the triazole agent fluconazole, it has been speculated that loading doses may improve pharmacodynamic target attainment rates. The use of voriconazole necessitates therapeutic drug monitoring and dose adjustments for patients with hepatic dysfunction. Neonates treated with lipid-based formulations of the polyene amphotericin B may be at an increased risk of death, such that alternative antifungal agents should be considered for neonates with invasive fungal infections. Alternative antifungal agents such as micafungin and caspofungin also exhibit unique pharmacokinetic considerations in this population. Neonates rapidly eliminate micafungin and require nearly three times the normal adult dose to achieve comparable levels of systemic exposure. Conversely, peak caspofungin concentrations have been reported to be similar among neonates and adults. However, both of these drugs feature favorable safety profiles. Recent studies with acyclovir have suggested that current dosing regimens may not result in therapeutic central nervous system concentrations and more frequent dosing may be required for neonates at later postmenstrual ages. Though ganciclovir and valganciclovir demonstrate excellent activity against cytomegalovirus, they are associated with significant neutropenia. In summary, many pharmacokinetic and pharmacodynamic studies have been conducted in this vulnerable population; however, there are also substantial gaps in our knowledge that require further investigation. These studies will be invaluable in determining optimal neonatal dosing regimens that have the potential to improve clinical outcomes and decrease adverse effects associated with antimicrobial and antiviral treatments