Effect of immediate neonatal zidovudine on prevention of vertical transmission of human immunodeficiency virus type 1

AbstractObjectives: To describe the effects of various short zidovudine (ZDV) prophylactic regimens on vertical transmission of human immunodeficiency virus type 1 (HIV-1) infection, especially the effect of immediate neonatal ZDV prophylaxis.Materials and Methods: The study included children of HIV-1-infected mothers who were born at a teaching hospital in Bangkok. The ZDV prophylaxis regimens varied by time periods that included: (1) no ZDV (1991–1996); (2) antenatal oral ZDV, 250 mg given twice a day starting at 34 to 36 weeks' gestation and continued until labor (1995–1998); (3) antenatal oral ZDV plus immediate neonatal oral ZDV, 6 mg/0.6 mL/dose started within the first 2 hours after birth and continued at 6-hour intervals for 4 to 6 weeks (1997–1998); and (4) intrapartum intravenous ZDV given in addition to regimen 3 (1998–1999). Neonatal ZDV was administered within 2 hours after birth in 95% of the neonates.Results: In a cohort of 136 children born at least 9 months before the analysis date, the HIV-1 vertical infection rates were: (1) no ZDV, 11 of 48 (22.9%, 95% confidence interval [Cl] = 12.0–37.3); (2) late antenatal ZDV, 10 of 47 (21.3%, 95% Cl = 10.7–35.7); (3) late antenatal ZDV plus immediate neonatal ZDV, 0 of 28 (0%, 95% Cl = 0–12.3); (4) late antenatal, intrapartum intravenous ZDV, plus immediate neonatal ZDV, 0 of 13 (0%, 95% Cl = 0–24.7). An estimated 0% (95% Cl = 0–8.6) of the infants who received immediate neonatal ZDV with or without intrapartum ZDV were infected, as compared with 22.1% (95% Cl = 14.2–31.8 ) of those who received no ZDV or only late antenatal ZDV (P < 0.001).Conclusion: The results of this study suggests high protective effect of immediate administration of neonatal ZDV. Perinatal components of antiretroviral prophylaxis provided the best results for protecting against vertical HIV-1 transmission

The treatment of a pregnant HIV positive patient with cryptococcal meningitis in Malawi. Case report and review of treatment options

This case reports cryptococcal meningitis in an HIV positive woman on antiretroviral therapy, presenting with left middle cerebral artery stroke at 30 weeks gestation. The patient had well-controlled HIV (CD4 count over 200 cells/mL). The immunosuppressive effects of the pregnancy likely contributed to the development of cryptococcal disease. The patient was successfully treated with two weeks of amphotericin B followed by fluconazole, delivered a healthy baby, but remained with a permanent severe neurological deficit

Nosocomial outbreak of neonatal Salmonella enterica serotype Enteritidis meningitis in a rural hospital in northern Tanzania

BACKGROUND: Clinicians at Haydom Lutheran Hospital, a rural hospital in northern Tanzania noted an unusually high case-fatality rate of pediatric meningitis and suspected an outbreak of an unknown agent or an organism resistant to the empirical therapy. METHODS: We established a provisional microbiology laboratory to investigate the suspected outbreak. Blood and spinal fluid specimens were taken from children below the age of seven years with suspected meningitis. The blood and spinal fluid specimens were inoculated in commercial blood culture bottles and locally prepared Thayer-Martin medium in slanted tubes, respectively. The bacterial isolates were sent to Norway for further investigation, including susceptibility testing and pulsed-field gel-electrophoresis (PFGE). RESULTS: Among 24 children with suspected meningitis and/or septicemia, five neonates had meningitis caused by Salmonella enterica serotype Enteritidis, all of whom died. Two children had S. Enteritidis septicemia without meningitis and both survived. Genotyping with PFGE suggested a clonal outbreak. The salmonella strain was resistant to ampicillin and sensitive to gentamicin, the two drugs commonly used to treat neonatal meningitis at the hospital. CONCLUSION: The investigation reminds us that nontyphoidal salmonellae can cause meningitis associated with very high case-fatality rates. Resistance to multiple antimicrobial agents increases the risk of treatment failure and may have contributed to the fatal outcome in all of the five patients with salmonella meningitis. The investigation indicated that the outbreak was nosocomial and the outbreak subsided after hygienic measures were instituted. Establishing a provisional microbiological laboratory is a valuable and affordable tool to investigate and control outbreaks even in remote rural areas

Comparative Tuberculosis (TB) Prevention Effectiveness in Children of Bacillus Calmette-Guérin (BCG) Vaccines from Different Sources, Kazakhstan

Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization.Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis.Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts.All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by manufacturer. When setting national immunization policy, consideration should be given to prevention effectiveness of BCG preparations

Adverse events in people taking macrolide antibiotics versus placebo for any indication

BACKGROUND: Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated. Because adverse events are treatment-specific, rather than disease-specific, it is possible to increase the number of adverse events available for analysis by combining randomised controlled trials (RCTs) of the same treatment across different diseases. OBJECTIVES:To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Acute Respiratory Infections Group Specialised Register (2018, Issue 4); MEDLINE (Ovid, from 1946 to 8 May 2018); Embase (from 2010 to 8 May 2018); CINAHL (from 1981 to 8 May 2018); LILACS (from 1982 to 8 May 2018); and Web of Science (from 1955 to 8 May 2018). We searched clinical trial registries for current and completed trials (9 May 2018) and checked the reference lists of included studies and of previous Cochrane Reviews on macrolides. SELECTION CRITERIA: We included RCTs that compared a macrolide antibiotic to placebo for any indication. We included trials using any of the four most commonly used macrolide antibiotics: azithromycin, clarithromycin, erythromycin, or roxithromycin. Macrolides could be administered by any route. Concomitant medications were permitted provided they were equally available to both treatment and comparison groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and collected data. We assessed the risk of bias of all included studies and the quality of evidence for each outcome of interest. We analysed specific adverse events, deaths, and subsequent carriage of macrolide-resistant bacteria separately. The study participant was the unit of analysis for each adverse event. Any specific adverse events that occurred in 5% or more of any group were reported. We undertook a meta-analysis when three or more included studies reported a specific adverse event. MAIN RESULTS: We included 183 studies with a total of 252,886 participants (range 40 to 190,238). The indications for macrolide antibiotics varied greatly, with most studies using macrolides for the treatment or prevention of either acute respiratory tract infections, cardiovascular diseases, chronic respiratory diseases, gastrointestinal conditions, or urogynaecological problems. Most trials were conducted in secondary care settings. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin.Most studies (89%) reported some adverse events or at least stated that no adverse events were observed.Gastrointestinal adverse events were the most commonly reported type of adverse event. Compared to placebo, macrolides caused more diarrhoea (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.34 to 2.16; low-quality evidence); more abdominal pain (OR 1.66, 95% CI 1.22 to 2.26; low-quality evidence); and more nausea (OR 1.61, 95% CI 1.37 to 1.90; moderate-quality evidence). Vomiting (OR 1.27, 95% CI 1.04 to 1.56; moderate-quality evidence) and gastrointestinal disorders not otherwise specified (NOS) (OR 2.16, 95% CI 1.56 to 3.00; moderate-quality evidence) were also reported more often in participants taking macrolides compared to placebo.The number of additional people (absolute difference in risk) who experienced adverse events from macrolides was: gastrointestinal disorders NOS 85/1000; diarrhoea 72/1000; abdominal pain 62/1000; nausea 47/1000; and vomiting 23/1000.The number needed to treat for an additional harmful outcome (NNTH) ranged from 12 (95% CI 8 to 23) for gastrointestinal disorders NOS to 17 (9 to 47) for abdominal pain; 19 (12 to 33) for diarrhoea; 19 (13 to 30) for nausea; and 45 (22 to 295) for vomiting.There was no clear consistent difference in gastrointestinal adverse events between different types of macrolides or route of administration.Taste disturbances were reported more often by participants taking macrolide antibiotics, although there were wide confidence intervals and moderate heterogeneity (OR 4.95, 95% CI 1.64 to 14.93; Iand#178; = 46%; low-quality evidence).Compared with participants taking placebo, those taking macrolides experienced hearing loss more often, however only four studies reported this outcome (OR 1.30, 95% CI 1.00 to 1.70; Iand#178; = 0%; low-quality evidence).We did not find any evidence that macrolides caused more cardiac disorders (OR 0.87, 95% CI 0.54 to 1.40; very low-quality evidence); hepatobiliary disorders (OR 1.04, 95% CI 0.27 to 4.09; very low-quality evidence); or changes in liver enzymes (OR 1.56, 95% CI 0.73 to 3.37; very low-quality evidence) compared to placebo.We did not find any evidence that appetite loss, dizziness, headache, respiratory symptoms, blood infections, skin and soft tissue infections, itching, or rashes were reported more often by participants treated with macrolides compared to placebo.Macrolides caused less cough (OR 0.57, 95% CI 0.40 to 0.80; moderate-quality evidence) and fewer respiratory tract infections (OR 0.70, 95% CI 0.62 to 0.80; moderate-quality evidence) compared to placebo, probably because these are not adverse events, but rather characteristics of the indications for the antibiotics. Less fever (OR 0.73, 95% 0.54 to 1.00; moderate-quality evidence) was also reported by participants taking macrolides compared to placebo, although these findings were non-significant.There was no increase in mortality in participants taking macrolides compared with placebo (OR 0.96, 95% 0.87 to 1.06; Iand#178; = 11%; low-quality evidence).Only 24 studies (13%) provided useful data on macrolide-resistant bacteria. Macrolide-resistant bacteria were more commonly identified among participants immediately after exposure to the antibiotic. However, differences in resistance thereafter were inconsistent.Pharmaceutical companies supplied the trial medication or funding, or both, for 91 trials. AUTHORS' CONCLUSIONS: The macrolides as a group clearly increased rates of gastrointestinal adverse events. Most trials made at least some statement about adverse events, such as "none were observed". However, few trials clearly listed adverse events as outcomes, reported on the methods used for eliciting adverse events, or even detailed the numbers of people who experienced adverse events in both the intervention and placebo group. This was especially true for the adverse event of bacterial resistance.</p

Rectal Carriage of Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacilli in Community Settings in Madagascar

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteria (ESBL-PE) emerged at the end of the 1980s, causing nosocomial outbreaks and/or hyperendemic situations in hospitals and long-term care facilities. In recent years, community-acquired infections due to ESBL-PE have spread worldwide, especially across developing countries including Madagascar. OBJECTIVES: This study aimed to determine the prevalence and risk factors of intestinal carriage of ESBL-PE in the community of Antananarivo. METHODS: Non-hospitalized patients were recruited in three health centers in different socio economic settings. Fresh stool collected were immediately plated on Drigalski agar containing 3 mg/liter of ceftriaxone. Gram-negative bacilli species were identified and ESBL production was tested by a double disk diffusion (cefotaxime and ceftazidime +/- clavulanate) assay. Characterization of ESBLs were perfomed by PCR and direct sequencing . Molecular epidemiology was analysed by Rep-PCR and ERIC-PCR. RESULTS: 484 patients were screened (sex ratio  = 1.03, median age 28 years). 53 ESBL-PE were isolated from 49 patients (carrier rate 10.1%). The isolates included Escherichia coli (31), Klebsiella pneumoniae (14), Enterobacter cloacae (3), Citrobacter freundii (3), Kluyvera spp. (1) and Pantoae sp.(1). In multivariate analysis, only the socioeconomic status of the head of household was independently associated with ESBL-PE carriage, poverty being the predominant risk factor. CONCLUSIONS: The prevalence of carriage of ESBL in the community of Antananarivo is one of the highest reported worldwide. This alarming spread of resistance genes should be stopped urgently by improving hygiene and streamlining the distribution and consumption of antibiotics

Clinical features, acute complications, and outcome of Salmonella meningitis in children under one year of age in Taiwan

<p>Abstract</p> <p>Background</p> <p><it>Salmonella </it>meningitis remains a threat to children below two years of age in both developing and developed countries. However, information on such infections has not been well characterized. We analyzed data related to twelve years of experience in order to clarify the comprehensive features of <it>Salmonella </it>meningitis in our patients, including admission characteristics, acute complications, and long-term outcome.</p> <p>Methods</p> <p>The records of patients with spontaneous <it>Salmonella </it>meningitis from 1982 to 1994 were retrospectively reviewed. The long-term outcome was prospectively determined for survivors at school age by the developmental milestones reported by their parents and detailed neurological evaluation along with intelligence, hearing, visual, speech and language assessments.</p> <p>Results</p> <p>Of the twenty-four patients, seizures were noted in fifteen (63%) before admission and thirteen (54%) during hospitalization. Acute complications mainly included hydrocephalus (50%), subdural collection (42%), cerebral infarction (33%), ventriculitis (25%), empyema (13%), intracranial abscess (8%), and cranial nerve palsy (8%). Three patients (13%) died during the acute phase of <it>Salmonella </it>meningitis. The twenty-one survivors, on whom we followed up at school age, have sequelae consisting of language disorder (52%), motor disability (48%), intelligence quotient < 80 (43%), epilepsy (33%), sensorineural hearing loss (17%), visual deficits (10%), abducens nerve palsy (5%), microcephaly (5%), and hydrocephalus (5%). Overall, good outcome was noted in six (28.6%) of twenty-one survivors, mild sequelae in three (14.2%), moderate in six (28.6%), and severe in six (28.6%).</p> <p>Conclusion</p> <p><it>Salmonella </it>meningitis in neonates and infants had a wide spectrum of morbidity and acute complications, leading to a complicated hospital course and subsequently a high prevalence of permanent adverse outcome. Thus, early recognition of acute complications of <it>Salmonella </it>meningitis and a follow-up plan for early developmental assessment of survivors are vital.</p

Multidrug-resistant Salmonella Typhimurium in Four Animal Facilities

Within each of 4 outbreaks of S. Typhimurium among humans and animals at companion animal care facilities, isolates were identical or nearly identical