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James A Berkley

Publications and source records attributed to James A Berkley.

10 recordsLinked to original sources

Decreasing prevalence of antimicrobial resistance in non-typhoidal Salmonella isolated from children with bacteraemia in a rural district hospital, Kenya.

We analysed 336 non-typhoidal Salmonella (NTS) isolated from children <13 years of age with bacteraemia admitted to a rural district hospital in Kenya from 1994 to 2005. Pulsed-field gel electrophoresis was used to determine genetic relatedness of strains, and antimicrobial susceptibility testing was also performed. Most NTS were either Salmonella enterica serovar Typhimurium (n=114; 33.9%) or S. enterica serovar Enteritidis (n=128; 38.1%), with minimal genotypic diversity over the study period. The NTS showed a remarkable decrease in levels of resistance especially to two commonly available antimicrobials (amoxicillin and co-trimoxazole), from high of 69.2% and 68.4% during 1994-1997 to 11% and 13%, respectively, in 2002-2005 (P<0.01). All NTS remained fully susceptible to cefotaxime and ciprofloxacin. Our findings show that commonly available drugs may still be useful for treatment of invasive NTS infections in this rural population.

Anti-Bacterial Agents↗

Salmonella bacteremia in Kenyan children.

BACKGROUND: Nontyphoidal Salmonella spp. are among the leading causes of childhood bacteremia in sub-Saharan Africa, yet there are few published clinical series, and the risk factors for acquiring infection are not fully understood. METHODS: We examined data from 166 cases of nontyphoidal Salmonella bacteremia identified during a large prospective study of bacteremia among all children admitted to a district hospital in Kenya. We also investigated the importance of comorbidities, including current malaria parasitemia, recent malaria (detectable Plasmodium falciparum histidine rich protein 2 in the absence of parasitemia), sickle cell disease, malnutrition and human immunodeficiency virus (HIV) infection. RESULTS: Nontyphoidal Salmonella bacteremia was associated with severe malnutrition (33% cases), HIV infection (18% cases), a history of illness >7 days, recent hospital admission, splenomegaly, anemia and recent (but not current) malaria but was not associated with diarrhea. Seventy-seven (46%) children with nontyphoidal Salmonella bacteremia fulfilled World Health Organization clinical criteria for a diagnosis of pneumonia. Independent risk factors for death were diarrhea, tachypnea, HIV infection, severe malnutrition, meningitis and young age. CONCLUSIONS: Clinical diagnosis of invasive nontyphoidal Salmonella infection in African children is difficult without microbiology facilities because clinical features overlap with other conditions. The common risk factors for nontyphoidal Salmonella infection differ from developed countries, with high a prevalence of malnutrition, HIV, malaria and anemia. Children with nontyphoidal Salmonella infection who fulfill World Health Organization clinical criteria for severe pneumonia may receive ineffective therapy in the form of penicillin.

Anemia↗

Children with severe malnutrition: can those at highest risk of death be identified with the WHO protocol?

BACKGROUND: With strict adherence to international recommended treatment guidelines, the case fatality for severe malnutrition ought to be less than 5%. In African hospitals, fatality rates of 20% are common and are often attributed to poor training and faulty case management. Improving outcome will depend upon the identification of those at greatest risk and targeting limited health resources. We retrospectively examined the major risk factors associated with early (<48 h) and late in-hospital death in children with severe malnutrition with the aim of identifying admission features that could distinguish a high-risk group in relation to the World Health Organization (WHO) guidelines. METHODS AND FINDINGS: Of 920 children in the study, 176 (19%) died, with 59 (33%) deaths occurring within 48 h of admission. Bacteraemia complicated 27% of all deaths: 52% died before 48 h despite 85% in vitro antibiotic susceptibility of cultured organisms. The sensitivity, specificity, and likelihood ratio of the WHO-recommended "danger signs" (lethargy, hypothermia, or hypoglycaemia) to predict early mortality was 52%, 84%, and 3.4% (95% confidence interval [CI] = 2.2 to 5.1), respectively. In addition, four bedside features were associated with early case fatality: bradycardia, capillary refill time greater than 2 s, weak pulse volume, and impaired consciousness level; the presence of two or more features was associated with an odds ratio of 9.6 (95% CI = 4.8 to 19) for early fatality (p < 0.0001). Conversely, the group of children without any of these seven features, or signs of dehydration, severe acidosis, or electrolyte derangements, had a low fatality (7%). CONCLUSIONS: Formal assessment of these features as emergency signs to improve triage and to rationalize manpower resources toward the high-risk groups is required. In addition, basic clinical research is necessary to identify and test appropriate supportive treatments.

Bacteremia↗

Invasive Gram-negative bacilli are frequently resistant to standard antibiotics for children admitted to hospital in Kilifi, Kenya.

OBJECTIVES: To determine the pattern of resistance among Gram-negative bacilli causing invasive bacterial disease for the antibiotics that are already in common use in Kilifi, Kenya and for two potential alternatives, ciprofloxacin and cefotaxime. Also, to determine whether prevalence and severity of resistance was increasing over time, to identify patients who are particularly at risk of resistant infections, and to explore which factors are associated with the development of resistance in our setting. METHODS: We used Etest to study antibiotic susceptibility patterns of 90 Gram-negative bacilli cultured in blood or CSF from paediatric inpatients over 8 years. RESULTS: Susceptibility to amoxicillin 28%, cefotaxime 95% and ciprofloxacin 99% did not vary significantly with age. Susceptibilities for isolates from children aged less than 14 days were: chloramphenicol, 81%; trimethoprim/sulfamethoxazole, 71%; and gentamicin, 91%. From older children, susceptibilities were: chloramphenicol, 62%; trimethoprim/sulfamethoxazole, 39%; and gentamicin, 73%. Chloramphenicol susceptibility was significantly more common among non-typhi salmonellae than other species (79% versus 53%, P < 0.0005). The combination of gentamicin and chloramphenicol covered 91% of all isolates. The prevalence of resistance did not increase over time and was not more common in patients with HIV or malnutrition. Age was the only clinical feature that predicted resistance. CONCLUSIONS: Gentamicin or chloramphenicol alone was suboptimal therapy for Gram-negative sepsis, although in this retrospective study, there was no association between resistance and mortality.

Anti-Bacterial Agents↗

Use of clinical syndromes to target antibiotic prescribing in seriously ill children in malaria endemic area: observational study.

OBJECTIVES: To determine how well antibiotic treatment is targeted by simple clinical syndromes and to what extent drug resistance threatens affordable antibiotics. DESIGN: Observational study involving a priori definition of a hierarchy of syndromic indications for antibiotic therapy derived from World Health Organization integrated management of childhood illness and inpatient guidelines and application of these rules to a prospectively collected dataset. SETTING: Kilifi District Hospital, Kenya. PARTICIPANTS: 11,847 acute paediatric admissions. MAIN OUTCOME MEASURES: Presence of invasive bacterial infection (bacteraemia or meningitis) or Plasmodium falciparum parasitaemia; antimicrobial sensitivities of isolated bacteria. RESULTS: 6254 (53%) admissions met criteria for syndromes requiring antibiotics (sick young infants; meningitis/encephalopathy; severe malnutrition; very severe, severe, or mild pneumonia; skin or soft tissue infection): 672 (11%) had an invasive bacterial infection (80% of all invasive bacterial infections identified), and 753 (12%) died (93% of all inpatient deaths). Among P falciparum infected children with a syndromic indication for parenteral antibiotics, an invasive bacterial infection was detected in 4.0-8.8%. For the syndrome of meningitis/encephalopathy, 96/123 (76%) isolates were fully sensitive in vitro to penicillin or chloramphenicol. CONCLUSIONS: Simple clinical syndromes effectively target children admitted with invasive bacterial infection and those at risk of death. Malaria parasitaemia does not justify withholding empirical parenteral antibiotics. Lumbar puncture is critical to the rational use of antibiotics.

Anti-Bacterial Agents↗

Bacteremia among children admitted to a rural hospital in Kenya.

BACKGROUND: There are few epidemiologic data on invasive bacterial infections among children in sub-Saharan Africa. We studied every acute pediatric admission to a rural district hospital in Kenya to examine the prevalence, incidence, types, and outcome of community-acquired bacteremia. METHODS: Between August 1998 and July 2002, we cultured blood on admission from 19,339 inpatients and calculated the incidence of bacteremia on the basis of the population served by the hospital. RESULTS: Of a total of 1783 infants who were under 60 days old, 228 had bacteremia (12.8 percent), as did 866 of 14,787 children who were 60 or more days of age (5.9 percent). Among infants who were under 60 days old, Escherichia coli and group B streptococci predominated among a broad range of isolates (14 percent and 11 percent, respectively). Among infants who were 60 or more days of age, Streptococcus pneumoniae, nontyphoidal salmonella species, Haemophilus influenzae, and E. coli accounted for more than 70 percent of isolates. The minimal annual incidence of community-acquired bacteremia was estimated at 1457 cases per 100,000 children among infants under a year old, 1080 among children under 2 years, and 505 among children under 5 years. Of all in-hospital deaths, 26 percent were in children with community-acquired bacteremia. Of 308 deaths in children with bacteremia, 103 (33.4 percent) occurred on the day of admission and 217 (70.5 percent) within two days. CONCLUSIONS: Community-acquired bacteremia is a major cause of death among children at a rural sub-Saharan district hospital, a finding that highlights the need for prevention and for overcoming the political and financial barriers to widespread use of existing vaccines for bacterial diseases.

Bacteremia↗

Progressive increase in antimicrobial resistance among invasive isolates of Haemophilus influenzae obtained from children admitted to a hospital in Kilifi, Kenya, from 1994 to 2002.

Etest susceptibilities to amoxicillin, chloramphenicol, and trimethoprim-sulfamethoxazole of 240 invasive isolates of Haemophilus influenzae cultured from children in rural Kenya were 66%, 66%, and 38%, respectively. Resistance increased markedly over 9 years and was concentrated among serotype b isolates. In Africa, the increasing cost of treating resistant infections supports economic arguments for prevention through conjugate H. influenzae type b immunization.

Anti-Bacterial Agents↗

Indicators of acute bacterial meningitis in children at a rural Kenyan district hospital.

OBJECTIVE: Acute bacterial meningitis remains an important cause of death and neurologic sequelae in African children. The clinical features of meningitis are often nonspecific and in this setting may overlap with those of malaria. Early diagnosis and appropriate antibiotic treatment are perhaps the most important steps in management, but published data suggest that fewer than half of the cases of childhood meningitis are identified at first assessment in hospitals in this region. The objective of this study was to identify clinical indicators of acute bacterial meningitis by examining components of the World Health Organization Integrated Management of Childhood Illness (IMCI) referral criteria for meningitis (lethargy, unconsciousness, inability to feed, stiff neck, or seizures) and other symptoms and signs. METHODS: Kilifi District Hospital, serving approximately 200,000 people in a rural, malaria-endemic area of the Kenyan coast, was studied. A Kenya Medical Research Institute research center is located at the hospital. All pediatric admissions aged > or =60 days between June 2001 and July 2002 were eligible. RESULTS: A total of 91 (2.0%) of 4582 admissions had meningitis, including 77 (4.0%) of 1929 of those who met the IMCI referral criteria for meningitis at admission (sensitivity: 85%; specificity: 59%). Independent indicators of the presence of meningitis were a bulging fontanel, neck stiffness, cyanosis, impaired consciousness, partial seizures, and seizures outside the febrile convulsions age range. One or more of these indicators was present in 895 (19%) of admissions, 72 (8.0%) of whom had meningitis (sensitivity: 79%; specificity: 80%). Independent indicators of the absence of meningitis were the absence of a history of fever, a history of diarrhea, and a positive malaria slide. The area under the receiver operating characteristic curve for a set of simple screening rules based on the positive indicators identified was 0.88 (95% confidence interval: 0.85-0.92). CONCLUSIONS: The presence of > or =1 of a bulging fontanel, neck stiffness, cyanosis, impaired consciousness, partial seizures, and seizures outside the febrile convulsions age range is a clear indication for lumbar puncture and/or presumptive treatment. However, careful observation and reassessment may be the only practical way to identify one fifth of meningitis cases in this setting.

Acute Disease↗