Methicillin-resistant Staphylococcus aureus (MRSA) isolates with vancomycin minimal inhibitory concentrations (MIC's) ≥ 1.5 μg/mL have been associated with poorer clinical outcomes and treatment failures in adults. We evaluated vancomycin MIC's in 71 invasive pediatric community-acquired MRSA (CA-MRSA) isolates from 2004-2008 using the E-test micro-method and the E-test macro-method. The modal MIC by micro-method was 1.5 μg/mL, and median vancomycin MIC's did not increase over time.
MRSA; vancomycin; methicillin resistance; Staphylococcus aureus; pediatric; invasive
Viral respiratory infections are among the most common reasons for hospitalization of children in the United States. Our objective was to compare molecular and conventional methods in a cohort of hospitalized children with and without symptoms of respiratory viral illness (RVI).
Retrospective cohort study of infants and toddlers hospitalized between December 2007 and March 2008 at Johns Hopkins Hospital. 569 of 641 patient visits (89%) were tested on admission. Conventional tests (immunochromatography, direct fluorescent antibody, shell vial, and tube culture) were performed on all patients and nucleic acid tests (NATs) were performed on available samples (n=306). Viruses were grouped into those routinely (Group 1) and those not routinely (Group 2) detected by conventional methods.
In children with RVI symptoms (N=148), NATs identified a virus in 83% specimens compared with 49% by conventional methods (p<0.001), but detected a similar percentage of specimens with Group 1 viruses (48.6% and 55.4%, p=0.13) compared with conventional tests. In children without RVI symptoms (N=158), NATs identified a virus in 41.7% specimens compared with 4.4% by conventional tests (p<0.001) and identified more Group 1 viruses (9.5% and 4.4%, p=0.03) compared with conventional tests. Group 2 viruses were identified by NATs in a similar percentage of symptomatic and asymptomatic patients (25% and 32.3%, p=0.20).
Molecular assays may have several advantages over conventional methods for detecting respiratory viruses, including improved sensitivity and rapid detection, but given the high prevalence of positive results in children without RVI symptoms, results should be interpreted cautiously.
molecular diagnostic methods; pediatric respiratory infections; nucleic acid tests; virus isolation
: There is limited information on antiretroviral (ARV) regimens and outcomes in perinatally HIV (PHIV) -infected youth. Substantial drug resistance after long-term ARV use and non-adherence hinder efforts to design suppressive regimens for PHIV-infected youth. This study compares clinical outcomes by expected activity of the prescribed ARV regimens.
A retrospective cohort study of 13-24 year-old PHIV-infected youth on stable ARV regimens for ≥ 6 months was conducted at a pediatric HIV clinic. ARV regimens were retrospectively categorized as optimal or suboptimal based on accumulated genotypic resistance prior to study regimen initiation.
Fifty-two patients with similar baseline characteristics met inclusion criteria (21 optimal and 31 suboptimal regimens). Patients on optimal regimens had significantly higher increases in CD4 than those on suboptimal regimens by week 48 of treatment (+62 vs. +8 cells/mm3, respectively; p = 0.04) and by the end of study period (+93 vs. –1 cells/mm3, respectively; p = 0.03). There were no significant differences between the groups in decline of viral load, frequency of opportunistic infections or hospitalizations, or accumulation of resistance mutations. Overall, 60% of the optimal and 45% of the suboptimal groups had non-adherence during the study regimen (p = 0.3).
PHIV-infected youth receiving optimal regimens had greater CD4 improvements but no difference in virologic outcomes compared to those on suboptimal regimens. In a patient population with significant non-adherence, providers must weigh the immunologic benefits of initiating an optimal regimen vs. the potential risks of further resistance accumulation limiting future treatment options.
human immunodeficiency virus; antiretroviral; perinatally HIV-infected youth
Effect of the 2009 H1N1 influenza pandemic on viral epidemiology of upper and lower respiratory tract infections (URI and LRI) in healthy infants in the first year of life has not been well studied.
A total of 180 healthy infants were enrolled from birth and monitored for occurrences of URI and its LRI and acute otitis media (AOM) complications until the first AOM episode or between 6 and 12 months of age. Nasopharyngeal specimens collected during acute respiratory illnesses were tested for 18 viruses.
Between October 2008 and April 2011, 373 URI episodes, including 20 with LRI, in 139 infants were documented. Viral studies were performed on 189 URI episodes; 87% were positive. Throughout the 31-month period (1386 patient-months), rhinovirus was the predominant virus causing URI (55%); RSV was the major cause of LRI (64%). While there was a significant increase in parent-initiated visit rate during the 15-month influenza pandemic as compared with pre- and post- pandemic periods, only 4 cases of influenza were detected (2 cases during and 2 cases pre- and post- pandemic).
The 2009 influenza A/H1N1 pandemic had no impact on the overall viral epidemiology of respiratory infections in healthy infants in the first year of life but resulted in increased parent-initiated visits due to respiratory symptoms. Maternal antibody and absence of co-morbidity may explain the low influenza burden while parental anxiety may explain the increased healthcare visit rate during the pandemic.
influenza; influenza pandemic; upper respiratory tract infection; lower respiratory tract infection; infants
Changes in oncology care and the diagnosis and management of influenza over the past several decades may have altered the epidemiology and outcomes of influenza in pediatric oncology patients.
The clinical features and outcomes of 102 pediatric patients undergoing cancer therapy during 107 episodes of influenza between January 2002 and April 2009 were retrospectively ascertained.
Median age at the time of influenza was 7.2 years [interquartile range (IQR) 3.8–11.2 years]; 46% of patients were male. Nineteen patients (18%) were recipients of hematopoietic stem cell transplants (HSCT). Patients’ median absolute neutrophil and lymphocyte counts were 1300/μL (IQR 500–2967/μL) and 360/μL (IQR 180–836/μL), respectively. Twelve patients (11%) had co-infections with influenza and one or more other respiratory pathogens. Influenza prompted patients’ hospitalization during 64% of episodes, and 75% received antiviral therapy. Complications occurred in 30% of infections and serious complications occurred in 7%. Three patients died, but no deaths were directly attributable to influenza. Most patients had delays in cancer therapy; the median delay was 5 days. Neutropenia, concurrent infection, increasing age and having received HSCT increased the risk of serious complications.
Advances in the management of pediatric cancer and influenza have not altered the epidemiology and outcome of influenza in oncology patients. Clinical features identify subgroups of patients with influenza who are at risk for poor outcomes and those with a good prognosis.
pediatric; influenza; cancer; immunocompromised host
We used a novel high resolution melting (HRM) diversity assay to analyze HIV diversity in Ugandan children (ages 0.6 to 12.4 years) who were enrolled in an observational study of antiretroviral treatment (ART). Children were maintained on ART if they were clinically and immunologically stable.
HIV diversity was measured prior to ART (baseline) in 76 children and after 48 or 96 weeks of ART in 14 children who were not virally suppressed. HIV diversity (expressed as HRM scores) was measured in six regions of the HIV genome (two in gag, one in pol, three in env).
Higher baseline HRM scores were significantly associated with older age (≥ 2 years, P ≤ 0.001 for all six regions). HRM scores from different regions were weakly correlated. Higher baseline HRM scores in three regions (one in gag, two in env) were associated with ART failure. HIV diversity was lower in four regions (two in gag, one in pol, one in env) after 48 to 96 weeks of non-suppressive ART compared to baseline.
Higher levels of HIV diversity were observed in older children prior to ART and higher levels of diversity in some regions of the HIV genome were associated with ART failure. Prolonged exposure to non-suppressive ART was associated with a significant decrease in viral diversity in selected regions of the HIV genome.
HIV; diversity; children; antiretroviral therapy
Limited data are available in Honduras describing the etiology and seasonality of respiratory infections, especially in rural outpatient settings. Better data may lead to improved therapeutic and preventative strategies. The goal of our study was to determine the viral etiology and seasonality of acute respiratory infections in a rural Honduran population of children.
Prospective clinic surveillance was conducted to identify children <5 years of age presenting with respiratory symptoms <5 days duration. We obtained data on age, sex, medical history, breastfeeding history, symptoms, risk factors, house hold setting, temperature, respiratory rate, and chest exam findings. To assess the association between specific viruses and weather, regional meteorological data were collected. Nasopharyngeal samples were tested for 16 respiratory viruses using a multiplex PCR panel.
From February 2010 through June 2011, 345 children <5 years of age were enrolled; 17%, 23%, 30%, and 31% were <6, 6–11, 12–23, and 24–60 months old, respectively. Including all clinics in the region, 44.5% of patients <5 years of age with documented respiratory diagnoses were enrolled. At least one virus was identified in 75.4% children, of which 7.5% were co-infections; 13.3% were positive for parainfluenza, 11.9% for influenza, 8.1% for human metapneumovirus (hMPV), and 7.5% for respiratory syncytial virus (RSV). Rainfall correlated with parainfluenza (p≤0.0001), influenza (p≤0.0001), hMPV (p= 0.0182), and RSV (p≤0.0001).
These results suggest that the spectrum of viruses in ill rural Honduran children is similar to that in North and Central America, though the seasonality is typical of some tropical regions.
viral respiratory infections; influenza; seasonality; Honduras; child
The epidemiology of pediatric tuberculosis (TB) from 1995–2000 in Harris County, TX has been previously reported. This study was conducted to evaluate the continued trends of Mycobacterium tuberculosis (MTB) clustering and the role of genotyping in pediatric TB.
Data came from the Houston Tuberculosis Initiative, a prospective population-based active surveillance and molecular epidemiology project. The study population consisted of TB patients ≤ 18 years of age diagnosed in Harris County, TX from 2000 to 2004. Available MTB isolates were characterized by IS6110 restriction fragment length polymorphism and spoligotyping.
103 pediatric TB cases were enrolled in the Houston Tuberculosis Initiative study from 2000–2004. Sixty-one (59%) patients had potential source cases. MTB isolates were available and genotyped for 36 pediatric cases; 27 (75%) were clustered into 22 different genotypes. Of the 20 genotyped patients with a potential source case, 16 (80%) were clustered. Genotypes matched the potential source case in 12 cases. Eleven of the 16 (69%) genotyped patients without a potential source case were clustered.
Compared with pediatric cases in 1995–2000, there was a significant increase in the number of patients with unknown potential source cases that were clustered within the Houston Tuberculosis Initiative database. Since genotypic clustering is associated with recent transmission, there appears to be a failure in the identification of potential source cases through contact tracing. Reduced funding of public health departments forces more limited TB control activities and therefore could pose a threat to TB control.
tuberculosis; pediatric; genotype; cluster
Varicella-zoster virus (VZV) is the first human herpesvirus to be attenuated and then approved in 1995 as a live vaccine for children. Within a few years after its administration in the United States, small outbreaks of breakthrough varicella were observed in vaccinees. Several risk factors were determined. But now a new investigation suggests another risk factor, namely, a deficiency in antibody responses to a specific individual VZV glycoprotein called gC (ORF14; gpV) in the vaccinees. Antibody concentrations to 5 VZV protein antigens were measured in children who had either wild type varicella or varicella vaccination.
These proteins included two major glycoproteins called gE (ORF68; gpI) and gC (ORF14), both constituents of the viral envelope and therefore potentially important targets of the adaptive immune response. Of particular interest, the serum antibody responses to VZV gC antigen were significantly lower in vaccinees than in children who had wild type varicella. In contrast, the serum antibody responses to VZV gE antigen were comparable in both groups. These data implied that relatively little gC antigen was produced in children who were immunized. Since abundant gC protein is produced in skin vesicles during wild type varicella, the lack of a vesicular rash after vaccination may limit the amounts of some viral antigens required for an optimal antibody response.
Vitamin D may help prevent adverse pediatric outcomes, including infectious diseases and growth failure, based on its role in immune and metabolic functions. We examined the association of maternal vitamin D status and pediatric health outcomes in children born to HIV-infected women.
Vitamin D status was determined in 884 HIV-infected pregnant women at 12 to 27 weeks of gestation in a trial of vitamin supplementation (not including vitamin D) in Tanzania. Information on child morbidities, anemia and hypochromic microcytosis, and anthropometry was recorded through monthly clinic visits. Generalized estimated equations and Cox proportional hazards models were used to assess the relationships of outcomes with maternal vitamin D status.
A total of 39% of women had low vitamin D levels (<32 ng/mL). Children born to women with low vitamin D status were 1.11 times more likely to report cough during follow-up (RR: 1.11; 95% CI: 1.02-1.21). No significant associations were noted for other respiratory symptoms, diarrhea, or anemia outcomes. Low maternal vitamin D status was associated with significantly increased risk of stunting (height-for-age z-score <-2; RR: 1.29; 95% CI: 1.05-1.59) and underweight (weight-for-age z-score <-2; RR: 1.33; 95% CI: 1.03-1.71).
Maternal vitamin D status may be an important risk factor for respiratory infections, and ensuring optimal growth in HIV-exposed children.
Vitamin D; Morbidity; Anemia; Growth; Children; HIV/AIDS
Kawasaki disease (KD) can be associated with gastrointestinal complications, including pancreatitis. We describe a child in whom infliximab infusion for IVIG-resistant KD coincided with marked clinical improvement of the patient’s acute pancreatitis.
vasculitis; coronary artery aneurysms; TNF-α; intravenous immunoglobulin; gallbladder hydrops
Candida infections are a leading cause of infectious disease-related death in infants supported with extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK), thus standard fluconazole dosing in children on ECMO may result in suboptimal drug exposure. This study determined the PK of fluconazole in infants on ECMO.
Infants <120 days old received either intravenous fluconazole prophylaxis (25 mg/kg once a week) or treatment (12 mg/kg daily) while on ECMO. Paired plasma samples were collected pre- and post-oxygenator around doses 1 and 2 to calculate PK indices and describe oxygenator extraction. A 1-compartment model was fit to the data using non-linear regression. Surrogate pharmacodynamic targets for efficacy were evaluated.
Ten infants were enrolled. After dose 1 (n=9), the median clearance was 17 mL/kg/h, the median volume of distribution was 1.5 L/kg, and the median exposure in the first 24 hours (AUC0–24) was 322 h*mg/L. After multiple doses (n=7), the median clearance was 22 mL/kg/h, the median volume of distribution was 1.9 L/kg, and the AUC0–24 was 352 h*mg/L. After dose 1, 78% of infants achieved the prophylaxis target, while only 11% achieved the therapeutic target. Oxygenator extraction of fluconazole was minimal (−2.0%, standard deviation 15.0), and extraction was not correlated with age of the ECMO circuit (rho= − 0.05). There were no adverse events related to fluconazole.
Infants on ECMO had higher volume of distribution but similar clearance when compared with historical controls not on ECMO. In infants on ECMO, a fluconazole dose of 25 mg/kg weekly provides adequate exposure for prophylaxis against Candida infections. However, higher doses may be needed for treatment.
fluconazole; Candida; extracorporeal membrane oxygenation; pharmacokinetics; infants
Substantial care variation occurs in a number of pediatric diseases.
We evaluated the variability in health care resource utilization and its association with clinical outcomes among children, aged 1–18 years, hospitalized with community acquired pneumonia (CAP). Each of 29 children’s hospitals contributing data to the Pediatric Hospital Information System was ranked based on the proportion of CAP patients receiving each of 8 diagnostic tests. Primary outcome variable was length of stay (LOS), re-visit to the ED or readmission within 14 days of discharge.
Of 21,213 children hospitalized with non-severe CAP, median age was 3 years (interquartile range [IQR], 1–6 years). Laboratory testing and antibiotic usage varied widely across hospitals; cephalosporins were the most commonly prescribed antibiotic. There were large differences in the processes of care by age categories. The median LOS was 2 days (IQR, 1–3 days) and differed across hospitals; 25% of hospitals had median LOS >= 3 days. Hospital-level variation occurred in 14-day ED visits and 14-day readmission, ranging from 0.9 to 4.9% and 1.5% to 4.4%, respectively. Increased utilization of diagnostic testing was associated with longer hospital LOS (p=0.036) but not with probability of 14-day readmission (Spearman’s ρ = 0.234; p=0.225). There was an inverse correlation between LOS and 14-day revisit to the ED (ρ=−0.48, p=0.013).
Wide variability occurred in diagnostic testing for children hospitalized with CAP. Increased diagnostic testing was associated with a longer LOS. Earlier hospital discharge did not correlate with increased 14-day readmission. The precise interaction of increased utilization with longer LOS remains unclear.
pneumonia; bacterial pneumonia; disease management; epidemiology; evidence-based medicine
Umbilical cord care varies often reflecting community or health-worker beliefs. We undertook a review of current evidence on topical umbilical cord care. Study quality was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system, and a meta-analysis was conducted for comparable trials. Available moderate-quality to high-quality evidence indicate that cord cleansing with 4% chlorhexidine may reduce the risk of neonatal mortality and sepsis (omphalitis) in low-resource settings.
cord care; chlorhexidine; neonatal mortality; sepsis; neonates
A survey of nasopharyngeal (NP) carriage of penicillin nonsusceptible pneumococcal (PNSp) isolates was conducted among 1,192 children attending 62 day care centers in Brazil, where pneumococcal vaccination has still not been introduced routinely. NP pneumococcal carriage was detected in 686 (57.6%) infants, and 178 (25.9%) of them carried PNSp isolates. Being less than 24 months of age, hospitalization in the previous three months, and recurrent acute otitis media were independently associated with PNSp. Serotypes 14, 23F, 19A, 6A, 6B and 19F were the most common serotype isolated accounting for 80% of the PNSp. A high proportion (35/332) of non(sero)-typeable isolates was detected, 62.9% of them PNSp. Serotypes coverage projected for the PCV13-valent vaccine (72%) was significantly higher compared to PCV7 (58.4%) and PCV10-valent vaccine (59.3%).
pneumococcal carriage; pneumococcal serotypes; nasopharyngeal carriage; day care centers; vaccine coverage; nonsusceptible pneumococcal
Among infants with prematurity and/or chronic lung disease for whom respiratory syncytial virus immunoprophylaxis is recommended, we examined adherence in infants enrolled during healthcare visits for acute respiratory illness in 3 US counties from 2001 to 2007. Immunoprophylaxis among infants who met national criteria for prophylaxis increased from 33% to 83% over the 6-year period; 17% (11/65) of infants who received immunoprophylaxis did not meet eligibility criteria.
respiratory syncytial virus; adherence; palivizumab
The frequency and duration of antibody responses after trivalent inactivated influenza vaccine (TIV) in young children are not well defined and assume greater importance with the expanded recommendations for vaccine use in children aged 6 months–5 years.
Forty-three children aged 6–23 months were vaccinated with TIV in the fall of 2002. At enrollment the majority of children were seronegative to one or more of the vaccine antigens and had no previously documented influenza. Postvaccination sera were collected in the subsequent fall and winter seasons. Acute antibody responses to TIV were determined using standardized hemagglutination inhibition (HAI) and neutralization assays. In calculating the duration of responses, sequential sera were analyzed to the last available sera, to the point at which antibody became undetectable, or to intercurrent influenza infection.
Forty-three subjects contributed 121 sera that were analyzed for HAI responses to TIV. Four-fold HAI rises after 2 doses of TIV in naive individuals were seen in 13 (72%) to H3N2, 22 (92%) to H1N1, and 15 (60%) to influenza B. Fewer 4-fold rises were seen in those with preexisting antibody. The results of microneutralization assays to H3N2 correlated well with HAI results. The time for antibody to decay to one-half of the postvaccination titer (t1/2) was approximately 126 days for H1N1 and 258 days for H3N2.
Although not all children responded with 4-fold rises in antibody or achieved the putative protective titer of ≥1:32, the half-life of antibody suggested that children immunized in the fall should have immune responses sustained throughout the ensuing influenza season.
influenza; vaccine; antibody
The influence of disease severity on cognitive and adaptive functioning in perinatally infected youth with (PHIV+/C) and without (PHIV+/NoC) a previous AIDS-defining illness (CDC Class C event), compared to perinatally exposed but uninfected youth (PHEU) is not well understood.
This was a cross-sectional analysis of cognitive and adaptive functioning in PHIV+/C (n=88), PHIV+/NoC (n=270), and PHEU (n=200) youth aged 7 to 16 years, from a multi-site prospective cohort study. Youth and caregivers completed the Wechsler Intelligence Scale for Children (WISC-IV) and the Adaptive Behavior Assessment System (ABAS-II) respectively. We compared means and rates of impairment between groups, and examined associations with other psychosocial factors.
Overall mean scores on measures of cognitive and adaptive functioning were in the low average range for all three groups. After adjustment for covariates, mean full scale IQ (FSIQ) scores were significantly lower for the PHIV+/C group than the PHIV+/NoC and PHEU groups (mean=77.8 vs 83.4 and 83.3, respectively), while no significant differences were observed between the PHEU and PHIV+/NoC groups in any domain. Lower cognitive performance for the PHIV+/C group was primarily attributable to a prior diagnosis of encephalopathy. No significant differences between groups were observed in adaptive functioning.
For long-term survivors, youth with HIV infection and a prior CDC class C event have higher risk for cognitive but not adaptive impairment regardless of current health status; this finding appears attributable to a previous diagnosis of encephalopathy. Early preventive therapy may be critical in reducing risk of later neurodevelopmental impairments.
Cognitive functioning; adaptive functioning; pediatric HIV infection; perinatal HIV exposure
Daptomycin is approved for the treatment of complicated skin and skin structure infections and Staphylococcus aureus bacteremia. We sought to characterize daptomycin single-dose pharmacokinetics and tolerability in young infants.
Subjects <120 days of age with suspected systemic infections were eligible for inclusion. Each subject was given a single 6 mg/kg intravenous dose of daptomycin. An average of 4 post-dose concentrations per infant was obtained.
Data from 20 infants are presented. Median gestational age at birth and postnatal age were 32 weeks (range 23, 40) and 3 days (1, 85), respectively. The median area under the concentration curve at 24 hours, volume of distribution, total body clearance, and half-life of daptomycin were 262.4 mg*h/L (166.7, 340.2), 0.21 L/kg (0.11, 0.34), 0.021 L/hr/kg (0.016, 0.034), and 6.2 hours (3.7, 9.0), respectively. No adverse events related to daptomycin were observed, including changes in creatine phosphokinase concentrations.
Daptomycin clearance in young infants was similar to that in 2–6-year-olds and higher than that observed in adolescents and adults.
daptomycin; complicated skin and skin structure infections; Staphylococcus aureus; pharmacokinetics
The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced into the Norwegian Childhood Immunization Program in 2006. A substantial effectiveness of PCV7 immunization against invasive pneumococcal disease has been demonstrated, while evidence of the impact on respiratory tract infections are less consistent.
This study included children participating in the Norwegian Mother and Child Cohort Study, which recruited pregnant women between 1999 and 2008. Maternal report of acute otitis media (AOM), lower respiratory tract infections (LRTIs) and asthma in the child was compared with PCV7 immunization status, as obtained from the Norwegian Immunization Registry. Generalized linear models with the log link function were used to report adjusted relative risks (RR) and 95% confidence intervals (CI).
For children who had received three or more PCV7 immunizations by 12 months of age, the adjusted relative risks of AOM and LRTIs between 12 and 18 months were 0.86 [95% CI: 0.81, 0.91] and 0.78 [95% CI: 0.70, 0.87] respectively, when compared with non-immunized children. A reduced risk of AOM, RR 0.92 [95% CI: 0.90, 0.94], and LRTIs, RR 0.75 [95%CI: 0.71, 0.80], between 18 and 36 months of age was also identified among children who had received 3 or more immunizations by 18 months. No association was seen between PCV7 immunization and asthma at 36 months of age.
Reduced incidence proportions of AOM and LRTIs before 36 months of age were observed among children immunized with PCV7 through the childhood immunization program.
Pneumococcal conjugate vaccination; lower respiratory tract infections; acute otitis media; asthma
In a randomized controlled trial, we administered seasonal trivalent inactivated influenza vaccine (TIV) or placebo to subjects 6–15 years of age in two consecutive years. Receipt of TIV in year 2 induced seroprotection in most subjects. Among 39 children who received TIV in the second year, receipt of TIV in the first year was associated with lower antibody titer rises in the second year to seasonal influenza A(H1N1) and A(H3N2) strains for which the vaccine strains remained unchanged. Antibody response to a different influenza B strain in the second year was unaffected by receipt of TIV in the first year.
vaccination; influenza; antibody response; children
Late presentation is common among African HIV-1-infected infants. Incidence and correlates of mortality were examined in 99 infants with HIV-1 diagnosis by age 5 months. Twelve-month survival was 66.8% (95% confidence interval, 55.9%, 75.6%). WHO stage 3/4, underweight, wasting, microcephaly, low hemoglobin, pneumonia, and gastroenteritis predicted mortality. Early HIV-1 diagnosis with ART before symptomatic disease is critical for infant survival.
Pediatric; Infant; HIV-1; Antiretroviral therapy; Mortality
The frequency or trajectory of vital sign abnormalities in children with pneumonia has not been described. In a cohort of 2,714 patients with severe pneumonia identified and treated as per the World Health Organization definition and recommendations, tachypnea, fever and hypoxia were found in 68.9%, 23.6% and 15.5% of children, respectively. Median oxygen saturation returned to a normal range by 10 hours following initiation of treatment, followed by temperature at 12 hours and respiratory rate at 22 hours for subjects less than 12 months and at 48 hours for those greater than or equal to 12 months of age.
pneumonia; vital signs; tachypnea; hypoxia; trajectory
Early-onset sepsis is an important cause of morbidity and mortality in neonates, and its diagnosis remains challenging. The complete blood cell count and differential have been previously evaluated as diagnostic tools for early-onset sepsis in small, single-center reports. We evaluated the diagnostic accuracy of the complete blood count and differential in early-onset sepsis in a large, multicenter population of neonates admitted to the neonatal intensive care unit.
Using a cohort of 166,092 neonates with suspected early-onset sepsis with cultures admitted to 293 neonatal intensive care units, we calculated odds ratios and receiver operating characteristic curves for complete blood cell count indices and prediction of a positive culture. We determined sensitivity, specificity, and likelihood ratios for various commonly used cut-off values from the complete blood cell count.
Low white blood cell counts, low absolute neutrophil counts, and high immature-to-total neutrophil ratios were associated with increasing odds of infection (highest odds ratios: 5.38, 6.84, and 7.97, respectively). Specificity and negative predictive values were high (73.7–99.9% and >99.8%). However, sensitivities were low (0.3–54.5%) for all complete blood cell count indices analyzed.
Low white blood cell count, absolute neutrophil count, and high immature-to-total neutrophil ratio were associated with increasing odds of infection, but no complete blood cell count-derived index possesses the sensitivity to rule out reliably early-onset sepsis in neonates.
neonatal; early-onset sepsis; blood cell count
Late-onset sepsis is an important cause of morbidity and mortality in infants. Diagnosis of late-onset sepsis can be challenging. The complete blood cell count and differential have been previously evaluated as diagnostic tools for late-onset sepsis in small, single-center reports.
We evaluated the diagnostic accuracy of the complete blood count and differential in late-onset sepsis in a large multicenter population.
Using a cohort of all infants with cultures and complete blood cell count data from a large administrative database, we calculated odds ratios for infection, as well as sensitivity, specificity, positive and negative predictive values, and likelihood ratios for various commonly used cut-off values.
High and low white blood cell counts, high absolute neutrophil counts, high immature-to-total neutrophil ratios, and low platelet counts were associated with late-onset sepsis. Associations were weaker with increasing postnatal age at the time of the culture. Specificity was highest for white blood cell counts <1000/mm3 and >50,000/mm3 (>99%). Positive likelihood ratios were highest for white blood cell counts <1000/mm3 (4.1) and platelet counts <50,000/mm3 (3.5).
No complete blood count index possessed adequate sensitivity to reliably rule out late-onset sepsis in this population.
neonatal; late-onset sepsis; blood cell count