Bloodstream infections in neonates with central venous catheters in three tertiary neonatal intensive care units in Pune, India.

BACKGROUND: Neonates admitted to the neonatal intensive care unit (NICU) are at risk for healthcare-associated infections, including central line-associated bloodstream infections. We aimed to characterize the epidemiology of bloodstream infections among neonates with central venous catheters admitted to three Indian NICUs. METHODS: We conducted a prospective cohort study in three tertiary NICUs, from May 1, 2017 until July 31, 2019. All neonates admitted to the NICU were enrolled and followed until discharge, transfer, or death. Cases were defined as positive blood cultures in neonates with a central venous catheter in place for greater than 2 days or within 2 days of catheter removal. RESULTS: During the study period, 140 bloodstream infections were identified in 131 neonates with a central venous catheter. The bloodstream infection rate was 11.9 per 1000 central line-days. Gram-negative organisms predominated, with 38.6% of cases caused by Klebsiella spp. and 14.9% by Acinetobacter spp. Antimicrobial resistance was prevalent among Gram-negative isolates, with 86.9% resistant to third- or fourth-generation cephalosporins, 63.1% to aminoglycosides, 61.9% to fluoroquinolones, and 42.0% to carbapenems. Mortality and length of stay were greater in neonates with bloodstream infection than in neonates without bloodstream infection (unadjusted analysis, p < 0.001). CONCLUSIONS: We report a high bloodstream infection rate among neonates with central venous catheters admitted to three tertiary care NICUs in India. Action to improve infection prevention and control practices in the NICU is needed to reduce the morbidity and mortality associated with BSI in this high-risk population.

Performance of Xpert® MTB/RIF and Xpert® Ultra for the diagnosis of tuberculous meningitis in children.

OBJECTIVE: To assess Xpert® MTB/RIF (Xpert) and Xpert® MTB/RIF Ultra (Ultra) performance in diagnosing pediatric tuberculous meningitis (TBM).METHODS: We conducted a study among children with suspected meningoencephalitis in Pune, India. Clinical, radiological, laboratory, and treatment data were analyzed to classify disease as definite, probable, possible or no TBM, using microbiologic or composite reference standards. We tested cerebrospinal fluid (CSF) either using Xpert or Ultra and estimated test performance characteristics.RESULTS: Of 341 participants, 149 (43.7%) were tested using Ultra and 192 (56.3%) with Xpert. Ultra had higher sensitivity (50% vs. 18%), lower specificity (91% vs. 99%), poor positive predictive value (PPV) (13% vs. 75%), and higher negative predictive value (NPV) (99% vs. 93%) than Xpert using the composite reference standard, with similar results by the microbiologic reference standard. Of 10 participants with trace positivity on Ultra, none met clinical TBM definitions.CONCLUSION: This is the first study to report on diagnostic performance of Ultra in pediatric TBM, which showed higher sensitivity and NPV than Xpert. For children presenting with nonspecific clinical features, Ultra is a promising diagnostic test. Further studies are required to define its optimal clinical use, including interpretation of trace positive results.

Short-range structure, the role of bismuth and property-structure correlations in bismuth borate glasses.

Bismuth-containing borate glasses, xBi2O3-(1 - x)B2O3, were synthesized in the broad composition range 0.20 ≤ x ≤ 0.80 by melting in Pt crucibles and splat-quenching between two metal blocks. Infrared reflectance spectra, measured in the range 30-5000 cm-1, were transformed into absorption coefficient spectra and then deconvoluted into component bands to probe the glass structure as a function of composition. Integrated intensities of bands above 800 cm-1 were used in combination with mass and charge balance equations to quantify the short-range borate structure in terms of the molar fractions X4m, X4o, X3, X2, X1 and X0 for borate units BØ4-, BØ2O23-, BØ3, BØ2O-, BØO22- and BO33-, where Ø and O- denote bridging and non-bridging oxygen atoms. Borate tetrahedral units were found to be present in both the meta-borate, BØ4-, and ortho-borate, BØ2O23-, forms with BØ4- constituting the dominating tetrahedral species for 0.20 ≤ x ≤ 0.70. The BØ2O23- units prevail at higher Bi2O3 levels (x > 0.7), and coexist with their isomeric triangular borate species BO33- (BØ2O23- ⇌ BO33-). The present IR results for the total molar fraction of borate tetrahedral units, X4 = X4m + X4o, are in very good agreement with reported NMR results for the fraction of boron atoms in four-fold coordination, N4. Besides evaluating X4m and X4o, the present work reports also for the first time the fractions of all types of triangular borate species X3-n with n = 0, 1, 2 and 3. The IR region below 550 cm-1 was found to be dominated by the Bi-O vibrational activity in coexisting ionic (160-230 cm-1) and distorted BiO6 sites (330-365 cm-1 and 475-510 cm-1), a result reflecting the dual role of Bi2O3 as glass-modifier and glass-former oxide. The latter role dominates in glasses exceeding 60 mol% Bi2O3, and is consistent with the extended glass formation in the bismuth-borate system. The structural results were used to calculate the average number of bridging B-Ø bonds per boron center, the average Bi-O and B-O single bond energy, and the atomic packing density of the studied glasses. These properties vary approximately linearly with Bi2O3 content in the three regimes 0.2 ≤ x ≤ 0.4, 0.4 < x ≤ 0.6 and 0.6 < x ≤ 0.83, and contribute collectively to the composition dependence of glass transition temperature.

Challenges in conducting trials for pediatric tuberculous meningitis: lessons from the field.

SETTING: TBM-KIDS is a phase I/II trial enrolling children with tuberculous meningitis (TBM) in three tertiary referral centers in India and Malawi.OBJECTIVE: To describe the challenges encountered in conducting the first randomized clinical trial of antimicrobial agents in pediatric TBM.DESIGN: The sources of the data were primarily monthly trial reports, non-enrollment case report forms, study diaries and registers maintained for recruitment, experiences shared by key team members during regular study calls and comments from site review visits. We reviewed, broadly categorized, and describe in detail the challenges encountered by study teams in trial implementation.RESULTS: Over 17 months, 3371 children with clinical presentations consistent with meningoencephalitis or undergoing lumbar puncture were assessed for eligibility; 21 (<1%) met enrollment criteria. We encountered challenges related to diagnosis, management of sick children, large catchment areas, adverse event attribution, concomitant medications, infrastructure requirements, expensive pediatric formulations with short expiry, and detection of treatment response in a highly variable disease across the age continuum. Training and adaptation of tools for neurocognitive and neurologic function assessment were necessary. Special care was undertaken to explain study participation to distraught caregivers and manage children longitudinally.CONCLUSION: Interventional trials in pediatric TBM are challenging but are critically important for improving the treatment of a disease that disables children physically, cognitively and emotionally. Sharing these challenges may help to address them more effectively as a TB research community and to advance treatments for this at-risk population.

Delays and barriers to early treatment initiation for childhood tuberculosis in India.

BACKGROUND: India accounts for 27% of global childhood tuberculosis (TB) burden. Understanding barriers to early diagnosis and treatment in children may improve care and outcomes.METHODS: A cross-sectional study was performed among 89 children initiated on anti-TB treatment from a public hospital in Pune during 2016, using a structured questionnaire and hospital records. Health care providers (HCPs) were defined as medical personnel consulted about the child's TB symptoms. Time-to-treatment initiation (TTI) was defined as the number of days between onset of TB symptoms and anti-TB treatment initiation. Based on Revised National TB Control Programme recommendations, delayed TTI was defined as >28 days.RESULTS: Sixty-seven (75%) of 89 enrolled children had significant TTI delays (median 51 days, interquartile range [IQR] 27-86). Sixty-six (74%) children visited 1-8 HCPs in the private sector before approaching the public sector. The median HCP delay was 28 days (IQR 10-75). Bacille Calmette-Guérin vaccination (aOR 10.96, P = 0.04) and loss of appetite (aOR 4.44, P = 0.04) were associated with delayed TTI.CONCLUSION: The majority of the children had TTI delays due to delays by HCPs in the private sector. Strengthening HCP competency in TB symptom screening and encouraging early referrals are crucial for rapid scaling up of early treatment initiation in childhood TB.

Barriers to screening and isoniazid preventive therapy for child contacts of tuberculosis patients.

BACKGROUND: India's guidelines recommend tuberculosis (TB) screening of household contacts aged <6 years and isoniazid preventive therapy (IPT) for children without active disease. We evaluated the current status and barriers to screening and IPT provision among the child contacts of TB patients. METHODS: Questionnaire and health record data were collected from index cases and health care providers (HCPs) at Sassoon General Hospital, Pune, India. RESULTS: Of 80 adult TB cases, 24 (30%) reported that an HCP recommended TB screening of their child contacts; 49/178 (28%) child contacts were screened. Sixteen (33%) children had active TB, and 28 (85%) of those who screened negative were prescribed IPT. Nineteen (76%) HCPs reported recommending child contact screening. Only 8 (32%) reported ever prescribing IPT. Lack of TB screening and IPT provision for child contacts was associated with inadequate HCP counseling (aOR 19.5, P < 0.001), a non-parent index case (aOR 3.72, P = 0.008) and lack of postgraduate HCP qualification (aOR 19.12, P = 0.04). CONCLUSIONS: TB screening and IPT provision for child contacts of adults with TB were infrequent. Many screened children had active TB. Universal, timely TB screening and IPT for exposed children are urgently needed to reduce pediatric TB in India.

Loss to follow-up and mortality among HIV-infected adolescents receiving antiretroviral therapy in Pune, India.

OBJECTIVES: India has the highest number of HIV-infected adolescents in Asia, but little is known about their treatment outcomes. We assessed rates and factors associated with loss to follow-up (LTFU) and mortality among Indian adolescents. METHODS: The analysis included adolescents (10-19 years old) starting antiretroviral therapy (ART) between 2005 and 2014 at BJ Government Medical College, Pune, India. LTFU was defined as missing more than three consecutive monthly visits. The competing-risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for LTFU, with death as the competing risk. Cox proportional hazard models were used to identify predictors of mortality. RESULTS: Of 717 adolescents starting ART, 402 with complete data were included in the analysis. Of these, 61% were male and 80% were perinatally infected, and the median baseline CD4 count was 174 cells/µL. LTFU and mortality rates were 4.4 and 4.9/100-person years, respectively. Cumulative LTFU incidence increased from 6% to 15% over 6 years. Age ≥ 15 years [adjusted SHR (aSHR) 2.44; 95% confidence interval (CI) 1.18-5.02] was a risk factor for LTFU. Cumulative mortality increased from 9.5% to 17.9% over 6 years. World Health Organization (WHO) stages III and IV [adjusted hazard ratio (aHR) 2.26; 95% CI: 1.14-4.48] and an increase in CD4 count by 100 cells/µL (aHR: 0.59; 95% CI: 0.43-0.83) were associated with mortality. CONCLUSIONS: A third of adolescents had been lost to follow-up or died by follow-up year 6. Older age was a risk factor for LTFU and advanced clinical disease for death. Strategies to improve retention counselling for older adolescents and closer clinical monitoring of all adolescents must be considered.

Chloroquine induced parkinsonism.

A case of parkinsonism is reported in a 5-years-old male child following prolonged use of chloroquine. The patient presented with reduced spontaneous movements and speech with an expressionless face and a parkinsonian gait but no tremors. His investigations including CT scan brain, CSF study and serum ceruloplasmin were normal. Chloroquine was discontinued and the patient was started on oral trihexyphenidyl. The patient showed gradual recovery and the drug was successfully withdrawn. The toxic manifestations were only transient and reversible.