Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia.

Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.

Promotion of Influenza Prevention Beliefs and Behaviors through Primary School Science Education.

BACKGROUND: School-based campaigns to improve student health have demonstrated short-term success across various health topics. However, evidence of the effectiveness of programs in promoting healthy beliefs and behaviors is limited. We hypothesized that educational curricula teaching the science behind health promotion would increase student knowledge, beliefs and adherence to healthy behaviors, in this case related to influenza. METHODS: Integrated Science Education Outreach is a successful education intervention in Rochester, Minnesota public schools that has demonstrated improvements in student learning. Within this program, we designed novel curricula and assessments to determine if gains in knowledge extended to influenza prevention. Further, we coupled InSciEd Out programming with a clinical intervention, Influenza Prevention Prescription Education (IPPE), to compare students' attitudes, intentions and healthy behaviors utilizing surveys and hand hygiene monitoring equipment. RESULTS: 95 students participated in (IPPE) in the intervention school. Talking drawings captured improvement in influenza prevention understanding related to hand washing [pre n=17(43%); post n=30(77%)] and vaccination [pre n=2(5%); post n=15(38%)]. Findings from 1024 surveys from 566 students revealed strong baseline understanding and attitudes related to hand washing and cough etiquette (74% or greater positive responses). Automated hand hygiene monitoring in school bathrooms and classrooms estimated compliance for both soap (overall median 63%, IQR 38% to 100%) and hand sanitizer use (0.04 to 0.24 uses per student per day) but did not show significant pre/ post IPPE differences. CONCLUSIONS: Student understanding of principles of influenza prevention was reasonably high. Even with this baseline, InSciEd Out and IPPE improved students' unprompted knowledge of behaviors to prevent influenza, as reflected by talking drawings. This novel metric may be more sensitive in capturing knowledge among students than traditional assessment methods. However, IPPE did not produce further significant differences in student attitudes and behaviors regarding the flu.

Epidemiology and outcome of Gram-negative bloodstream infection in children: a population-based study.

Population-based studies of Gram-negative bloodstream infection (BSI) in children are lacking. Therefore, we performed this population-based investigation in Olmsted County, Minnesota, to determine the incidence rate, site of acquisition, and outcome of Gram-negative BSI in children aged ⩽18 years. We used Kaplan-Meier method and Cox proportional hazard regression for mortality analysis. We identified 56 unique children with Gram-negative BSI during the past decade. The gender-adjusted incidence rate of Gram-negative BSI per 100 000 person-years was 129·7 [95% confidence interval (CI) 77·8-181·6]) in infants, with a sharp decline to 14·6 (95% CI 6·0-23·2) and 7·6 (95% CI 4·3-10·9) in children aged 1-4 and 5-18 years, respectively. The urinary tract was the most commonly identified source of infection (34%) and Escherichia coli was the most common pathogen isolated (38%). Over two-thirds (68%) of children had underlying medical conditions that predisposed to Gram-negative BSI. The overall 28-day and 1-year all-cause mortality rates were 11% (95% CI 3-18) and 18% (95% CI 8-28), respectively. Younger age and number of underlying medical conditions were associated with 28-day and 1-year mortality, respectively. Nosocomial or healthcare-associated acquisition was associated with both 28-day and 1-year mortality.

The association between the timing of valve surgery and 6-month mortality in left-sided infective endocarditis.

OBJECTIVE: The optimal timing of valve surgery in left-sided infective endocarditis (IE) is undefined. We aimed to examine the association between the timing of valve surgery after IE diagnosis and 6-month mortality among patients with left-sided IE. METHODS: We analysed data from a retrospective cohort of patients with left-sided IE who underwent valve surgery within 30 days of diagnosis at a tertiary centre. The association between time from IE diagnosis to surgery and all-cause 6-month mortality was assessed using Cox proportional hazards modelling after adjusting for the propensity score (to undergo surgery 0-11 days vs >11 days, median time, after IE diagnosis). RESULTS: Of 546 left-sided IE cases seen between 1980 and 1998, 129 (23.6%) underwent valve surgery within 30 days of diagnosis. The median time between IE diagnosis and surgery was 11 days (range 1-30). There were 35/129 (27.2%) deaths in the surgical group. Using Cox proportional hazards modelling, propensity score and longer time to surgery (in days) were associated with unadjusted HRs of (1.15, 95% CI 1.04 to 1.28, per 0.10 unit change, p = 0.009) and (0.93; 95% CI 0.88 to 0.99, per day, p = 0.03), respectively. In multivariate analysis, a longer time to surgery was associated with an adjusted HR (0.97; 95% CI 0.90 to 1.03). The propensity score and time from diagnosis to surgery had a correlation coefficient of r = -0.63, making multicollinearity an issue in the multivariable model. CONCLUSION: On univariate analysis, a longer time to surgery showed a significant protective effect for the outcome of mortality. After adjusting for the propensity to undergo surgery early versus late, a longer time to surgery was no longer significant but remained in the protective direction. Multicollinearity between the time to surgery and the propensity score may have hindered our ability to detect the independent effect of time to surgery.

Reducing infections among women undergoing cesarean section in Colombia by means of continuous quality improvement methods.

BACKGROUND: Improving obstetric care in resource-limited countries is a major international health priority. OBJECTIVE: To reduce infection rates after cesarean section by optimizing systems of obstetric care for low-income women in Colombia by means of quality improvement methods. METHODS: Multidisciplinary teams in 2 hospitals used simple methods to improve their systems for prescribing and administering perioperative antibiotic prophylaxis. Process indicators were the percentage of women in whom prophylaxis was administered and the percentage of these women in whom it was administered in a timely fashion. The outcome indicator was the surgical site infection rate. RESULTS: Before improvement, prophylaxis was administered to 71% of women in hospital A; 24% received prophylaxis in a timely fashion. Corresponding figures in hospital B were 36% and 50%. Systems improvements included implementing protocols to administer prophylaxis to all women and increasing the availability of the antibiotic in the operating room. These improvements were associated with increases in overall and timely administration of prophylaxis (P<.001) in both hospitals by time series analysis, with adjustment for volume and case mix. After improvement, overall and timely administration of prophylaxis was 95% and 96% in hospital A and 89% and 96% in hospital B. In hospital A, the surgical site infection rate decreased immediately after the improvements (P<.001). In hospital B, the infection rate began a downward trend before the improvements that continued after their implementation (P =.04). CONCLUSION: Simple quality improvement methods can be used to optimize obstetric services and improve outcomes of care in resource-limited settings.

An international survey of practice variation in the use of antibiotic prophylaxis in cesarean section.

OBJECTIVE: To examine the use of antibiotic prophylaxis in cesarean section in different countries and in relation to a reference regimen. METHOD: Fifty consecutive cesarean sections performed in eight centers in five countries were surveyed. Data from each center were compared to a regimen recommended by the Cochrane Collaboration (one dose of ampicillin or cefazolin administered to all women shortly before the procedure or immediately after cord clamping) using logistic regression with adjustment for procedure type. RESULT: Prophylaxis was used widely, but only four centers administered prophylaxis to all women. Ampicillin and cefazolin were the principal antibiotics used, but broad-spectrum agents and multidrug regimens were also used commonly. Only two centers reliably administered the antibiotic at the appropriate time. The majority of women received only one dose of antibiotic in only three centers. CONCLUSION: The use of antibiotic prophylaxis in cesarean section was variable and often at odds with published recommendations.

Transmission and control of infections in out-of-home child care.

The epidemiology of infections associated with out-of-home child care is well-known, but our understanding of cost-effective prevention strategies is limited. Existing studies indicate that multidimensional interventional programs can reduce infection rates, but these conclusions are limited by a variety of methodologic concerns. Important areas for future research are to determine the critical elements of effective intervention programs, whether improvements in infection rates can be sustained over long periods and the costs of implementing and sustaining these programs.

Risk-adjusted infection rates in surgery: a model for outcome measurement in hospitals developing new quality improvement programmes.

Assessment of healthcare quality is a major challenge in countries such as Hungary where there is limited experience with measurement of patient outcomes. We sought to develop the capacity for valid outcome measurement in Hungarian hospitals using surgical site infection (SSI) surveillance as a model and to identify areas for improvement by comparing SSI rates in Hungarian hospitals to benchmarks published by the United States Centers for Disease Control and Prevention's National Nosocomial Infection Surveillance (NNIS) System. We surveyed the incidence of SSI among 5126 patients undergoing 6006 procedures in 20 public hospitals in Hungary during 1996 using the Hospitals in Europe Link for Infection Control through Surveillance (HELICS) protocol, a protocol consistent with the methods used by the NNIS System. Cholecystectomy, herniorrhaphy, appendectomy, and open reduction of fracture--four of the five most commonly performed procedures in Hungary in 1996--comprised 85% of the procedures analysed. Cumulative SSI rates for herniorrhaphy and appendectomy were comparable to NNIS System benchmarks. Cumulative SSI rates for cholecystectomy were significantly higher in Hungarian hospitals among risk categories that included open procedures. Nearly half of the hospitals had SSI rates for cholecystectomy that were high outliers (>90% percentile) compared to NNIS System benchmarks. Cumulative SSI rates for open reduction of fracture and mastectomy were significantly higher in Hungarian hospitals due to high rates in a few hospitals. The duration of surgery for all procedure types was substantially shorter in Hungarian hospitals compared with NNIS System hospitals. Future work should focus on optimizing prevention strategies for patients undergoing cholecystectomy, open reduction of fracture, and mastectomy. The effect of the utilization of open vs. laparoscopic cholecystectomy, short procedure duration, and procedure volume on SSI rates should be evaluated further. This programme expanded the capacity of Hungarian hospitals to perform surgical site infection surveillance and can serve as a model for hospitals in other countries with limited experience with outcome measurement.

Cerebrospinal fluid pleocytosis and prognosis in invasive meningococcal disease in children.

BACKGROUND: The absence of cerebrospinal fluid (CSF) pleocytosis in invasive meningococcal disease (IMD) has been associated with an increased risk of death. It is unknown whether patients who lack a cellular response to central nervous system (CNS) infection are at the same risk of adverse outcome as patients who lack CNS infection. OBJECTIVES: To determine the frequency of presentation and outcome of three groups of children with IMD: Group 1, children with CSF pleocytosis; Group 2, children without CSF pleocytosis and with negative CSF cultures (bacteremia alone); and Group 3, children without CSF pleocytosis but with positive CSF cultures (CNS infection without CSF pleocytosis). METHODS: We reviewed the medical records of children with IMD at four pediatric referral hospitals between 1985 and 1996. Clinical and laboratory indices and severe adverse outcomes (defined as death or limb loss) were compared in the three groups. Multivariable logistic regression analysis was performed to determine whether CNS infection without CSF pleocytosis was independently associated with adverse outcome in IMD. RESULTS: Three hundred seventy-seven children with IMD were identified. Eighty-six patients were excluded because their CSF analysis either was not done or was unevaluable; of these patients 22 (25.6%) had an adverse outcome. Of the 291 evaluable patients 204 (70.1%) had CSF pleocytosis, 52 (17.9%) had bacteremia alone and 35 (12.0%) had CNS infection without CSF pleocytosis. Patients with CNS infection without CSF pleocytosis had significantly lower white blood cell and platelet counts and more coagulopathy than patients with bacteremia alone (P < or = 0.05) or patients with CSF pleocytosis (P < or = 0.01). The frequency of adverse outcome was 40% for patients with CNS infection without CSF pleocytosis compared with 9.6% for patients with bacteremia alone (P = 0.001) and 3.4% for patients with CSF pleocytosis (P < 0.001). CNS infection without CSF pleocytosis was independently associated with adverse outcome by multivariable logistic regression analysis (P = 0.003). CONCLUSIONS: Approximately 30% of all children with IMD present without CSF pleocytosis. Of these patients those with CNS infection without pleocytosis are at higher risk of adverse outcome than either patients with CSF pleocytosis or patients with bacteremia alone.

Hospital infection prevention and control: a model for improving the quality of hospital care in low- and middle-income countries.

Continuous quality improvement (CQI) is a powerful methodology for improving clinical outcomes and patient satisfaction while reducing inefficiency and costs. However, most hospitals in low- and middle-income countries have little experience with CQI methods. Hospital infection prevention is an ideal model for nascent efforts to improve the quality of hospital care because of its proven efficacy in reducing the occurrence of infections that compromise patient outcomes and increase costs. This article describes the design and implementation of a demonstration project to reduce the incidence of surgical-site infections (SSIs) for hospitals with little experience with quality-improvement methods. The project has a high likelihood of producing measurable reductions in SSI rates and hospital costs related to inefficient use of perioperative antimicrobial prophylaxis. Moreover, participating staff will gain experience that can be applied to efforts to improve the quality of other aspects of hospital care.

Infection control in countries with limited resources.

Considerable progress has been made in the development of effective hospital infection control programs in countries with limited resources, most notably in Asia and Latin America. National nosocomial infection surveillance methods are now used in a variety of countries, particularly in Brazil, and offer a better measure for evaluating the rates of common nosocomial infections and gauging the effect of prevention efforts. Extending these achievements to other hospitals that presently lack effective programs is an organizational and logistic challenge for the future. Newer, daunting problems are the prevention and control of antimicrobial resistance and nosocomial transmission of tuberculosis. Improvements in the protection of healthcare workers from exposure to bloodborne pathogens, research regarding the safety and efficacy of the reuse of single-use items, and more practical and affordable methods for sterilization and disinfection are needed.

Control of nosocomial antimicrobial-resistant bacteria: a strategic priority for hospitals worldwide.

The rapid emergence and dissemination of antimicrobial-resistant microorganisms in hospitals worldwide is a problem of crisis dimensions. The root causes of this problem are multifactorial, but the core issues are clear. The emergence of antimicrobial resistance is highly correlated with selective pressure that results from inappropriate use of antimicrobial agents. Dissemination of resistant organisms is facilitated by person-to-person transmission due to inconsistent application of basic infection control practices by hospital personnel. While control strategies exist, the interventions are not likely to be successful unless hospital leaders assume the responsibility for control of antimicrobial resistance. Strategic goals for the control of resistant organisms should be formulated on the basis of multidisciplinary input from hospital personnel. Processes and outcomes relevant to these strategic goals should be measured, and the resultant data should be used to design, implement, and evaluate systematic measures to increase the appropriate use of antimicrobial agents and basic infection control practices. This approach is as relevant to hospitals in countries with limited resources as it is to in fully industrialized countries.

Multivariable predictive models for adverse outcome of invasive meningococcal disease in children.

For prediction of adverse outcome (AO, defined as death or limb amputation) of invasive meningococcal disease (IMD) in children, two multivariable models were derived and validated by reviewing the data in the medical records of patients with IMD, who ranged from birth to 19 years of age, at three pediatric referral hospitals between 1985 and 1990 (derivation set, n = 153, 19 AO) and between 1991 and 1994 (validation set, n = 92, 11 AO). Variables in the derivation set significantly associated with AO (p < 0.05) were entered into a logistic regression analysis. Because coagulation studies (prothrombin time, partial thromboplastin time, and serum fibrinogen concentration) were available for only 50% of patients, two analyses were performed, either excluding (model 1) or including (model 2) coagulation studies. These analyses identified an absolute neutrophil count less than 3000/mm3, poor perfusion, and a platelet count less than 150,000/mm3 (model 1), and a serum fibrinogen concentration less than 2.5 gm/L (250 mg/dl) and an absolute neutrophil count less than 3000/mm3 (model 2), as independent predictors of AO (p < 0.05). When the models were tested on the validation set, the presence of at least two of the three predictors in model 1 had a sensitivity of 82% and a specificity of 97% in predicting AO; the presence of both predictors in model 2 had a sensitivity of 89% and a specificity of 97%. These models can reliably identify patients with IMD at high risk of AO for whom consideration of novel therapies is justified.

Shigellosis in neonates and young infants.

To determine the clinical features and outcome of shigellosis in young infants, we reviewed the hospital records of 159 infants < or = 3 months of age (including 30 neonates) and 159 children 1 to 10 years of age with shigellosis who were admitted to the Diarrhoea Treatment Centre in Dacca, Bangladesh. Infants more commonly had a history of nonbloody diarrhea (82.8% vs 42.7%; p < 0.001), moderate or severe dehydration (59.9% vs 32.1%; p < 0.001), or bacteremia (12.0% vs 5.0%; p = 0.027) and less commonly had fever (32.7% vs 58.6%; p < 0.001), abdominal tenderness (1.9% vs 12.6%; p < 0.001), or rectal prolapse (0% vs 8.3%; p = 0.001). Infections caused by Shigella boydii (20.8% vs 6.3%; p < 0.001) and Shigella sonnei (7.5% vs 1.3%; p = 0.006) were more common, and Shigella dysenteriae type 1 (9.4% vs 31.4%; p < 0.001) infections were less common in infants than in older children; the proportion of Shigella flexneri infections was equivalent in the two groups (59.1% vs 60.4%). Infants were twice as likely to die as older children (16.4% vs 8.2%; p = 0.026). Only 17 infants (14.3%) were being exclusively breast fed at the onset of their illness. In a multiple logistic regression analysis, independent predictors of death in infants were gram-negative bacteremia, ileus, decreased bowel sounds, hyponatremia, hypoproteinemia, and a lower number of erythrocytes detected on microscopic examination of stool specimens. Diarrhea management algorithms that rely only on clinical findings of dysentery to diagnose and treat shigellosis are likely to be unreliable in this high-risk age group.

PIP: Findings are reported from a study conducted to determine the clinical features and outcome of shigellosis in young infants. The authors reviewed the hospital records of 159 infants of no greater than age 3 months and those of 159 children aged 1-10 years with shigellosis who were admitted to the Diarrhea Treatment Center in Dacca, Bangladesh. 82.8% of infants had a history of nonbloody diarrhea, 59.9% moderate or severe dehydration, 12% bacteremia, 32.7% fever, 1.9% abdominal tenderness, and 0% rectal prolapse. 42.7% of children had a history of nonbloody diarrhea, 32.1% moderate or severe dehydration, 5.0% bacteremia, 58.6% fever, 12.6% abdominal tenderness, and 8.3% rectal prolapse. Infections caused by Shigella boydii and Shigella sonnei were more common in infants, while Shigella dysenteriae type 1 infections were less common in infants than in older children. There was an equivalent proportion of Shigella flexneri infections in the two groups. Infants were twice as likely to die as older children. Only 17 infants were being exclusively breastfed at the onset of their illness. Multiple logistic regression analysis identified the independent predictors of death among infants to be gram-negative bacteremia, ileus, decreased bowel sound, hyponatremia, hypoproteinemia, and a lower number of erythrocytes detected on the microscopic examination of stool specimens. Diarrhea management algorithms which rely exclusively upon clinical findings of dysentery to diagnose and treat shigellosis are likely to be unreliable in this high-risk age group.

Inhibitory substances produced by Streptococcus salivarius and colonization of the upper respiratory tract with group A streptococci.

It has been proposed that inhibitory substances produced by viridans streptococci colonizing the upper respiratory tract aid in eradication of established group A streptococcal colonization of that site. We studied the prevalence of inhibitory-substance producing strains of Streptococcus salivarius in throat cultures from three groups of children: 16 children with persistently positive throat cultures for group A streptococci despite receiving recommended therapeutic courses of antibiotics (group I), 26 children from whom group A streptococci were eradicated from the upper respiratory tract by antibiotic therapy (group II), and 18 children who never harboured group A streptococci in their upper respiratory tract during the study period (group III). An in vitro deferred antagonism method was employed to detect inhibitory substances; 5233 strains of S. salivarius were examined. Strains of S. salivarius producing inhibitory substances were isolated from 76-88% of the children in each group on at least one occasion. However, only a small percentage of subjects in each group harboured strains producing these substances in every throat culture. The mean total percentage of S. salivarius strains producing inhibitory substances was 21.8% in children in group I, 22.4% in children in group II, and 16.4% in children in group III; these percentages were not statistically different (P greater than 0.1). In this study, we could not confirm a significant role for inhibitory substances produced by S. salivarius in the eradication of group A streptococci from the upper respiratory tract of colonized individuals.