Browsing by Author "Kurtzhals, J."
Now showing 1 - 5 of 5
Results Per Page
Sort Options
Item Amikacin Treatment With or Without Aminophylline in Neonates with Suspected Sepsis at Korle-Bu Teaching Hospital: A Pharmacokinetic and Pharmacodynamic Study(University of Ghana, 2015-07) Amponsah, S. K.; Obeng Adjei, G.; Kurtzhals, J.; Enweronu-Laryea, C.; University of Ghana, College of Health Sciences, School of Pharmacy, Department of Pharmacology and ToxicologyBackground: Sepsis is a major cause of death among neonates. In neonates, symptoms of sepsis are often non-specific and diagnosis requires a high index of suspicion. Thus, the role of additional diagnostic markers is important. Amikacin is used as first-line treatment of neonatal sepsis and it is usually co-administered with aminophylline in preterm neonates in Ghana. Amikacin dosing is well established, however, optimal effect requires specific dose titration and maintenance therapy should be individualized. Aim: To describe the PK and evaluate selected aspects of the PD of amikacin in neonates with suspected sepsis. Methods: Neonates with suspected sepsis (n=322) and requiring amikacin or amikacin with aminophylline treatment were recruited at the Neonatal Intensive Care Unit, Korle-Bu Teaching Hospital, Ghana. Admission clinical and demographic information was collected, using case record forms. Blood culture and sensitivity, selected hematological (FBC), and biochemical [urea, creatinine, total bilirubin, C-reactive protein (CRP) and procalcitonin (PCT)] parameters were measured before treatment. A standard dose of amikacin was administered as per local guidelines. Brainstem auditory evoked potential was done before treatment commencement and seven days later in a randomly selected group of neonates. Serum amikacin concentration was measured at specified times after treatment initiation and amikacin concentration data was analyzed, using population PK modeling. Results: A total of 163 (50.6%) of admitted neonates were born preterm, of which 14 (4.3%) were extreme preterm. A total of 79 (24.5%) had signs/symptoms consistent with birth asphyxia. There was 13.6% (41/302) culture positivity. Among neonates categorized as having ―highly probable‖, ―probable‖ or ―less probable‖ sepsis, mean PCT was significantly different (P<0.001). The sensitivity, PPV, NPV and AUC was higher compared with CRP. The proportion of neonates with elevated PCT on admission was significantly higher in the ―highly probable‖ group compared with the ―probable group‖ [91% (20/22 versus 31.6% (6/19), p<0.001]. Overall mortality was 12%, with case fatality being highest among extreme preterms or those with birth weight less than 1 kg, or with elevated PCT. A total of 419 plasma concentration profile data was available for 247 neonates for population pharmacokinetic modeling. A one-compartment model best fitted amikacin disposition. The mean peak amikacin serum concentration was 20.56+8.7 μg/mL, and trough 6.68+3.86 μg/mL. Neonates administered amikacin with or without aminophylline showed varying CL and V, but with a high BSV, suggesting possible lack of effect of aminophylline co-administration on amikacin disposition. The population clearance (CL), and volume of distribution (V) of amikacin were related as: CL = 0.153 (birth weight/2.5)1.31, V = 2.94 (birth weight/2.5)1.18, with 58.9 and 50.7% between-subject variability in clearance and volume, respectively. Mean half-life (t1/2) of amikacin was 13.6 hours. There was no difference in the baseline and follow-up BAEP of neonates who received amikacin and those who did not. Conclusion: Birth weight was an important predictor of amikacin CL and V. Co-administration of aminophylline with amikacin did not influence the pharmacokinetics of amikacin. There was a relatively large V and long t1/2 of amikacin in recruited neonates. No difference existed in baseline and follow-up BAEP results of neonates treated with amikacin, although one subject showed a high BAEP threshold post-amikacin dose. PCT was a more sensitive marker than CRP in the diagnosis of early onset neonatal sepsis.Item Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose(Ghana Medical Journal 43(3):135-8, 2009) Adjei, G.O.; Goka, B.Q.; Rodrigues, O.P.; Hoegberg, L.C.; Alifrangis, M.; Kurtzhals, J.A case of an acute dystonic reaction in a child presumptively treated for malaria with amodiaquine, and a case of persistent asymptomatic bradycardia in another child with mild pulmonary stenosis treated with a standard dose of amodiaquine for parasitologically confirmed uncomplicated malaria, is reported. Both subjects were homozygous for the wild type allele of cytochrome P450 2C8, the main enzyme responsible for amodiaquine metabolism. In both subjects, plasma concentrations of N-desethylamodiaquine and N-bis-desethylamodiaquine, the main metabolites of amodiaquine, were normal. No other drugs were detectable in the plasma of these two subjects after further toxicological screening. These observations, which suggest altered metabolism in the subject with an acute dystonic reaction, support the assertion that amodiaquine-associated dystonia is an idiosyncratic reaction. However, the occurrence of bradycardia after a standard dose of amodiaquine, which coincided with the time of expected peak concentrations of the active metabolite of amodiaquine, suggests a direct drug effect. These less reported adverse effects are likely to increase in parallel with the increased use of amodiaquine as a partner drug for combination therapy of malaria in Ghana. Further studies aimed at elucidating the mechanisms underlying these effects are, therefore, required.Item Comparison of chloroquine with artesunate in the treatment of cerebral malaria in Ghanaian children(Journal of Tropical Pediatrics, 2001-06) Goka, B.Q.; Adabayeri, V.; Ofori-Adjei, E.; Quarshie, B.; Asare-Odei, G.; Akanmori, B.D.; Kurtzhals, J.; Ofori-Adjei, D.; Neequaye, J.Despite previously reported chloroquine-resistant forms of P. falciparum in Ghana, chloroquine remains the drug of choice in severe malaria. Artemisinin derivatives have been shown to be effective against chloroquine-resistant strains in other endemic areas. This open randomized study was conducted to compare the efficacy of chloroquine and artesunate in the treatment of childhood cerebral malaria. Out of 82 subjects that fulfilled the inclusion criteria, 36 were randomized to receive chloroquine and 46 to receive artemisinin. Blantyre coma scores, temperature and parasitaemia were monitored. Mortality and neurological deficits were documented. There was no difference in mortality rates (chloroquine, 16.7 per cent; artesunate, 21.7 per cent; p = 0.6), neurological deficit at day 14 (chloroquine, 0 per cent; artesunate, 4.3 per cent; p = 0.3), resolution of fever (p = 0.55), and coma recovery time (p = 0.8), between the two groups. The results suggest that syrup chloroquine and intramuscular/oral artesunate currently give comparable clinical responses in the treatment of cerebral malaria in Ghana. Possible reasons for this are discussed, and suggestions are made for future antimalarial drug policy.Item Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia(2012-08-01) Boeuf, Philippe S.; Loizon, S.; Awandare, G. A.; Tetteh, John K.A.; Addae, M.M.; Adjei, G.O.; Goka, B.; Kurtzhals, J.; Puijalon, O.; Hviid, L.; Akanmori, B.D.; Behr, C.Abstract Background Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients. Methods The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR+ and/or CD69+ surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. Results Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69+ and HLA-DR+ T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001). Conclusions These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection.Item Knowledge, attitudes and practices regarding antimicrobial use and resistance among healthcare seekers in two tertiary hospitals in Ghana: a quasi experimental study(BMJ Open, 2023) Otieku, E.; Fenny, A.P.; Labi, A-K.; Owusu-Ofori, A.K.; Kurtzhals, J.; Enemark, U.Objective To evaluate knowledge of antimicrobial resistance (AMR), to study how the judgement of health value (HVJ) and economic value (EVJ) affects antibiotic use, and to understand if access to information on AMR implications may influence perceived AMR mitigation strategies. Design A quasi-experimental study with interviews performed before and after an intervention where hospital staff collected data and provided one group of participants with information about the health and economic implications of antibiotic use and resistance compared with a control group not receiving the intervention. Setting Korle-Bu and Komfo Anokye Teaching Hospitals, Ghana. Participants Adult patients aged 18 years and older seeking outpatient care. Main outcome measures We measured three outcomes: (1) level of knowledge of the health and economic implications of AMR; (2) HVJ and EVJ behaviours influencing antibiotic use and (3) differences in perceived AMR mitigation strategy between participants exposed and not exposed to the intervention. Results Most participants had a general knowledge of the health and economic implications of antibiotic use and AMR. Nonetheless, a sizeable proportion disagreed or disagreed to some extent that AMR may lead to reduced productivity/indirect costs (71% (95% CI 66% to 76%)), increased provider costs (87% (95% CI 84% to 91%)) and costs for carers of AMR patients/societal costs (59% (95% CI 53% to 64%)). Both HVJ-driven and EVJ-driven behaviours influenced antibiotic use, but the latter was a better predictor (reliability coefficient >0.87). Compared with the unexposed group, participants exposed to the intervention were more likely to recommend restrictive access to antibiotics (p<0.01) and pay slightly more for a health treatment strategy to reduce their risk of AMR (p<0.01). Conclusion There is a knowledge gap about antibiotic use and the implications of AMR. Access to AMR information at the point of care could be a successful way to mitigate the prevalence and implications of AMR.