Nalini Singh

Changing Epidemiology of Clostridium difficile -Associated Disease in Children

OBJECTIVE To determine temporal trends in the incidence rate for Clostridium difficile-associated disease (CDAD) in a pediatric patient population. METHODS We performed an observational, retrospective cohort study that included children who visited or were admitted to Childrens National Medical Center during the period from July 2001 through June 2006. The CDAD incidence rates were determined and examined for changes over time using the Poisson regression method. RESULTS A total of 513 patients whose stool specimens tested positive for C. difficile toxin were identified. Of these patients, 61% were children aged 2 years or older. The proportion of patients with CDAD in this age group has steadily increased from 46% in 2001 to 64% in 2006. Largely as a result of an increasing number of cases of community-associated CDAD, the incidence of CDAD increased significantly in the outpatient setting, particularly in the emergency department (1.18 cases per 1,000 visits in 2001 vs 2.47 cases per 1,000 visits in 2006; P=.02). The incidence among inpatients decreased during the study period (1.024 cases per 1,000 patient-days in 2001 vs 0.680 cases per 1,000 patient-days in 2006; P=.004). In the neonatal intensive care unit, C. difficile toxin was detected in stool specimens collected from 22 patients aged from 15 days to 6 months. CONCLUSION This study revealed a steady increase in the number of patients seen in the emergency department with community-acquired CDAD. Findings from this study suggest that the characteristics of CDAD in children--a population that has not been considered to be at high risk for this disease in the past--are changing. Further investigations are warranted to explore deviations from the established burdens of the disease and patient risk factors.

Clinical and economic impact of methicillin-resistant Staphylococcus aureus colonization or infection on neonates in intensive care units.

OBJECTIVE The rising incidence and mortality of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in children has become a great concern. This study aimed to determine the clinical and economic impact of MRSA colonization or infection on infants and to measure excess mortality, length of stay, and hospital charges attributable to MRSA. DESIGN This is a retrospective cohort study. SETTING AND PATIENTS The study included infants admitted to a level III-IV neonatal intensive care unit from September 1, 2004, through March 31, 2008. METHODS A time-dependent proportional hazard model was used to analyze the association between MRSA colonization or infection and mortality. The relationships between MRSA colonization or infection and length of stay and between MRSA colonization or infection and hospital charges were assessed using a matched cohort study design. RESULTS Of 2,280 infants, 191 (8.4%) had MRSA colonization or infection. Of 132 MRSA isolates with antibiotic susceptibility results, 106 were resistant to clindamycin and/or trimethoprim-sulfamethoxazole, thus representing a noncommunity phenotype. The mortality rate was 17.8% for patients with MRSA colonization or infection and 11.5% for control subjects. Neither MRSA colonization (hazard ratio [HR], 0.9 [95% confidence interval {CI}, 0.5-1.5]; P > .05 ) nor infection (HR, 1.2 [95% CI, 0.7-1.9]; P > .05 ) was associated with increased mortality risk. Infection caused by MRSA strains that were resistant to clindamycin and/or trimethoprim-sulfamethoxazole increased the mortality risk by 40% (HR, 1.4 [95% CI, 0.9-2.2]; P > .05 ), compared with the mortality risk of control subjects, but the increase was not statistically significant. MRSA infection independently increased length of stay by 40 days (95% CI, 34.2-45.6; P < .001) and was associated with an extra charge of

Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

164,301 (95% CI,

Control of vancomycin-resistant enterococci in the neonatal intensive care unit.

158,712-

Outbreak of invasive disease caused by methicillin-resistant Staphylococcus aureus in neonates and prevalence in the neonatal intensive care unit.

169,889; P < .001). CONCLUSIONS MRSA colonization or infection in infants is associated with significant morbidity and financial burden but is not independently associated with increased mortality.

A stepwise approach to control an outbreak and ongoing transmission of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit

BACKGROUND The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. METHODS We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. FINDINGS We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacteriums total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier. INTERPRETATION Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae, and H pylori. FUNDING World Health Organization.

Characterizing vancomycin-resistant enterococci in neonatal intensive care.

BACKGROUND AND OBJECTIVE Multidrug-resistant organisms (MDROs), such as vancomycin-resistant enterococci (VRE), cause serious infections, especially among high-risk patients in NICUs. When VRE was introduced and transmitted in our NICU despite recommended infection control practices, we instituted active surveillance cultures to determine their efficacy in detecting and controlling spread of VRE among high-risk infants. METHODS Active surveillance cultures, other infection control measures, and a mandatory in-service education module on preventing MDRO transmission were implemented. Cultures were performed on NICU admission and then weekly during their stay. Molecular DNA fingerprinting of VRE isolates facilitated targeting efforts to eliminate clonal spread of VRE. Repetitive sequence PCR (rep-PCR)-based DNA fingerprinting was used to compare isolates recovered from patients with VRE infection or colonization. Environmental VRE cultures were performed around VRE-colonized or -infected patients. DNA fingerprints were prepared from the products of rep-PCR amplification and analyzed using software to determine strain genetic relatedness. RESULTS Active surveillance cultures identified 65 patients with VRE colonization or infection among 1,820 admitted to the NICU. Rep-PCR performed on 60 VRE isolates identified 3 clusters. Cluster 1 included isolates from 21 patients and 4 isolates from the environment of the index patient. Clusters 2 and 3 included isolates from 23 and 3 patients, respectively. Similarity coefficients among the members of each cluster were 95% or greater. CONCLUSIONS Control of transmission of multi-clonal VRE strains was achieved. Active surveillance cultures, together with implementation of other infection control measures, combined with rep-PCR DNA fingerprinting were instrumental in controlling VRE transmission in our NICU.

Molecular and Descriptive Epidemiology of Multidrug‐Resistant Enterobacteriaceae in Hospitalized Infants

Objectives To describe an outbreak of severe invasive disease caused by methicillin-resistant Staphylococcus aureus (MRSA) and the epidemiology of MRSA in a neonatal intensive care unit during a 12-yr period from 1989 to 2001. Setting A 40-bed, level III neonatal intensive care unit at a children’s hospital that admits approximately 450 neonates each year from about 35 neighboring hospitals. Patients All neonates infected or colonized with MRSA during the outbreak are described. All cases of MRSA infection or colonization in the neonatal intensive care unit from 1989 to 2001 were identified from the database maintained by the hospital epidemiology program. Results During the outbreak, 12 neonates were infected or colonized with MRSA, 11 of whom had the epidemic strain. Seven of these 11 neonates had invasive disease, including bacteremia, meningitis, or urinary tract infection, and four neonates were colonized with the epidemic strain. This outbreak was difficult to control by routine epidemiologic measures, and additional control measures, including closing the neonatal intensive care unit to new admissions and treating all infants with intranasal mupirocin, were implemented. Since the outbreak, the prevalence of MRSA in the neonatal intensive care unit has remained low. Conclusions MRSA outbreaks in neonatal intensive care units can be prolonged. Aggressive infection-control measures are often necessary to terminate these outbreaks. Such efforts are essential because MRSA infections in premature neonates can cause significant morbidity and mortality.

Treatment of drug-resistant Shigella infections

BACKGROUND Preventing methicillin-resistant Staphylococcus aureus (MRSA) transmission in health care facilities where MRSA is endemic is challenging yet critical. OBJECTIVE We sought to determine the effectiveness of 2 bundles of interventions for preventing MRSA transmission in a neonatal intensive care unit (NICU). METHODS This retrospective cohort study included infants admitted to our NICU between September 1, 2004, and March 31, 2009. Following a MRSA outbreak between September 2004 and September 2005, preventing ongoing MRSA transmission remained a challenge. In July 2006, bundle-I, including culture-based active surveillance, preemptive contact precaution for up to 72 hours for new admissions, and cohorting assignment of direct caregivers was introduced for eradicating MRSA transmission. Bundle-II began in April 2007 and included bundle-1 measures except that the real-time polymerase chain reaction test replaced culture for the detection of MRSA. RESULTS This study identified 218 infants who developed MRSA infection or colonization and 151 instances of MRSA transmission during the study period. After instituting bundle-II, the transmission rate declined from 2.9 to 2.1 per 1000 patient-days-at-risk (incidence rate ratio, 1.4; 95% confidence interval: 0.9-2.2), and hospital-acquired MRSA infections declined from 1.3 to 0.5 per 1000 patient-days-at-risk (incidence rate ratio, 2.5; 95% confidence interval: 1.1-5.8). CONCLUSION Despite an increasing incidence of MRSA in community settings, preventing MRSA transmission within a NICU is achievable through implementation of optimal intervention strategies.

Improving hand hygiene compliance in health care workers: Strategies and impact on patient outcomes.

Repetitive sequence–based polymerase chain reaction fingerprinting was used to characterize 23 vancomycin-nonsusceptible enterococcal isolates from 2003 to 2004. Five genetically related clusters spanned geographically distinct referring centers. DNA fingerprinting showed infant-to-infant transmission from referring institutions. Thus, community healthcare facilities are a source of vancomycin-nonsusceptible enterococci and should be targeted for increased infection control efforts.