Antimicrobial Prophylaxis In Children Research Articles

A Process Improvement Project to Increase Compliance With Cephalosporin-based Surgical Antimicrobial Prophylaxis in Children With Non-severe Penicillin Allergies

Background/purposeCephalosporins are considered safe and first-line prophylaxis in children with non-severe penicillin allergies. However, use of second-line agents is common and is primarily driven by poor allergic response documentation and misunderstanding of cross-reactivity risk. The goal of this project was to improve compliance with cephalosporin prophylaxis through improved documentation and targeted educational efforts. MethodsA multidisciplinary working group including representatives from allergy, surgery, infectious disease, and pharmacy developed staged interventions to facilitate compliance with cephalosporin prophylaxis. These included: (1) caregiver outreach to clarify incomplete allergy documentation, (2) a decision-support algorithm for prophylaxis use in penicillin-allergic patients, (3) standardized educational resources for surgical faculty and rotating trainees, (4) email reminders with prophylaxis recommendations sent out prior to scheduled cases, and (5) EMR-based decision support during antibiotic ordering. Rates of complete allergy documentation and cephalosporin utilization were compared for general surgery procedures between a 12-month pre-intervention and 14-month post-intervention period. Results578 patients with penicillin allergies recorded in the EMR were included (301 pre-intervention and 277 post-intervention), 54.0% of which received prophylaxis. Compared to the pre-intervention period, complete documentation of allergic reactions increased from 57.1% to 84.2% (p < 0.001) following implementation of all interventions. Appropriate prophylaxis utilization increased from 34.5% to 88.5% following implementation of all interventions (p < 0.001), and evidence of a stepwise increase in appropriate utilization was evident with each intervention stage. Persistent compliance failures during the post-implementation period were most commonly associated with urgent and emergent add-on cases. No adverse events or allergic responses were reported before or after project implementation. ConclusionsCompliance with cephalosporin prophylaxis significantly improved following a multidisciplinary effort targeting education, allergy documentation, and clinical support at the point of care. Ongoing efforts include postoperative audits within 24 h for noncompliant cases in order to identify barriers and improve compliance for urgent and emergent add-on cases. Level of EvidenceIII. Type of StudyProspective.

Swiss recommendations on perioperative antimicrobial prophylaxis in children.

Infection following surgical procedures leads to significant morbidity and mortality in all age groups. Sterile techniques, antibiotic prophylaxis and improved postoperative wound care have contributed to the decline of surgical site infections since the early days of surgery. Recommendations on the use of perioperative antimicrobial prophylaxis exist for adults, but are rare for the paediatric population. Here, we provide a standardised approach to the effective use of antimicrobial agents for the prevention of surgical site infections in children contributing to a targeted and rational perioperative use of antibiotics in Switzerland.

Nasopharyngeal Carriage and Antibiogram of Pneumococcal and Other Bacterial Pathogens from Children with Sickle Cell Disease in Tanzania.

BackgroundBacterial infections contribute significantly to morbidity and mortality in sickle cell disease (SCD) patients, particularly children under five years of age. In Tanzania, prophylaxis against pneumococcal infection among children with SCD advocates the use of both oral penicillin V (PV) and pneumococcal vaccines (PNV). Therefore, this study aimed to investigate nasopharyngeal carriage and antibiogram of Streptococcal pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) in children with SCD in Tanzania.MethodsThis cross-sectional study was undertaken at the two Sickle Pan-African Research Consortium (SPARCO) study sites in Dar es salaam, Tanzania. The study was conducted for six months and enrolled children with SCD between the ages of 6 to 59-months. A semi-structured questionnaire was used to collect patient data. Nasopharyngeal swabs were collected from all participants and cultured for Streptococcal pneumoniae and other bacterial isolates. Antimicrobial susceptibility tests of the isolates were done using the disc diffusion method.ResultsOut of 204 participants, the overall prevalence of bacterial carriage was 53.4%, with S. aureus (23.5%), coagulase-negative Staphylococci (CoNS) (23%) and S. pneumoniae (7.8%) being commonly isolated. In antibiotic susceptibility testing, S. aureus isolates were most resistant to penicillin (81.8%), whereas 81.3% of S. pneumoniae isolates were resistant to co-trimoxazole. The least antimicrobial resistance was observed for chloramphenicol for both S. aureus and S. pneumoniae isolates (6.3% versus 0%). The proportion of multi-drug resistance (MDR) was 66.7% for S. aureus isolates and 25% for S. pneumoniae isolates.ConclusionThere are substantially high nasopharyngeal carriage pathogenic bacteria in children with SCD in Dar es Salaam, Tanzania. The presence of MDR strains to the commonly used antibiotics suggests the need to reconsider optimizing antimicrobial prophylaxis in children with SCD and advocacy on pneumococcal vaccines.

Antimicrobial Prophylaxis and Modifications of the Gut Microbiota in Children with Cancer.

In children with cancer, chemotherapy can produce cytotoxic effects, resulting in immunosuppression and an augmented risk of febrile neutropenia and bloodstream infections. This has led to widespread use of antibiotic prophylaxis which, combined with intensive chemotherapy treatment, could have a long-term effect on the gastrointestinal microbiome. In this review, we aimed to analyze the current literature about the widespread use of antibiotic prophylaxis in children experiencing infectious complications induced by chemotherapy and its effects on the gut microbiome. Our review of the literature shows that antimicrobial prophylaxis in children with cancer is still a trending topic and, at the moment, there are not enough data to define universal guidelines. Children with cancer experience long and painful medical treatments and side effects, which are associated with great economic and social burdens, important psychological consequences, and dysbiosis induced by antibiotics and also by chemotherapy. Considering the importance of a healthy gut microbiota, studies are needed to understand the impact of dysbiosis in response to therapy in these children and to define how to modulate the microbiome to favor a positive therapeutic outcome.

Cost-Utility of Antimicrobial Prophylaxis for Treatment of Children With Vesicoureteral Reflux.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR.Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged <6 years diagnosed with VUR after a first UTI, considering these treatment strategies: (1) prophylaxis for all children with VUR, (2) prophylaxis for children with Grade III or Grade IV VUR, (3) prophylaxis for children with Grade IV VUR, and (4) no prophylaxis. Costs and effectiveness were estimated over the patient's lifetime. We used $100,000/QALY gained as the threshold for considering a treatment strategy cost effective.Results: Based on current data and plausible ranges to account for data uncertainty, prophylaxis of children with Grades IV VUR costs $37,903 per QALY gained. Treating children with Grade III and IV VUR costs an additional $302,024 per QALY gained. Treating children with all grades of VUR costs an additional $339,740 per QALY gained.Conclusions: Treating children with Grades I, II, and III VUR with long-term antimicrobial prophylaxis costs substantially more than interventions typically considered economically reasonable. Prophylaxis in children with Grade IV VUR is cost effective.

Urinary Tract Infections in Infants and Children.

Urinary tract infections (UTI) are one of the most common infections in children and symptoms may be nonspecific. The risk of renal scarring is highest in children under 1 year of age with febrile UTI and high-grade vesicoureteral reflux (VUR). Although treatment of UTI is usually straightforward, given increased rates of antimicrobial resistance worldwide, the choice of treatment for pediatric UTI should be guided by community resistance patterns whenever feasible. The benefit of antimicrobial prophylaxis after first UTI and/or in the presence of VUR remains controversial, but a recent meta-analysis supports continuous antimicrobial prophylaxis in children with VUR, indicating a need for more research in this area.

Reliability of grading of vesicoureteral reflux and other findings on voiding cystourethrography

Voiding cystourethrography (VCUG) is the modality of choice to diagnose vesicoureteral reflux (VUR). Although grading of VUR is essential for prognosis and clinical decision-making, the inter-observer reliability for grading has been shown to vary substantially. The Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) trial provides a large cohort of children with VUR to better understand the reliability of VCUG findings. To determine the inter-observer consistency of the grade of VUR and other VCUG findings in a large cohort of children with VUR. The RIVUR trial is a randomized controlled trial of antimicrobial prophylaxis in children with VUR diagnosed after UTI. Each enrollment VCUG was read by a local clinical (i.e. non-reference) radiologist, and independently by two blinded RIVUR reference radiologists. Reference radiologists' disagreements were adjudicated for trial purposes. The grade of VUR and other VCUG findings were extracted from the local clinical radiologist's report. The unit of analysis included individual ureters and individual participants. We compared the three interpretations for grading of VUR and other VCUG findings to determine the inter-observer reliability. Six-hundred and two non-reference radiology reports from 90 institutions were reviewed and yielded the grade of VUR for 560 left and 524 right ureters. All three radiologists agreed on VUR grade in only 59% of ureters; two of three agreed on 39% of ureters; and all three disagreed on 2% of ureters (Table). Agreement was better (≥92%) for other VCUG findings (e.g. bladder shape "normal"). The non-reference radiologists' grade of VUR differed from the reference radiologists' adjudicated grade by exactly one grade level in 19% of ureters, and by two or more grade levels in 2.2% of ureters. When the participant was the unit of analysis, all three radiologists agreed on the grade of VUR in both ureters in just 43% of cases. Our study shows considerable and clinically relevant variability in grading VUR by VCUG. This variability was consistent when comparing non-reference to the adjudicated reference radiologists' assessment and the reference radiologists to each other. This study was limited to children with a history of UTI and grade I-IV VUR and may not be generalizable to all children who have a VCUG. The considerable inter-observer variability in VUR grading has both research and clinical implications, as study design, risk stratification, and clinical decision-making rely heavily on grades of VUR.

Bladder Volume at Onset of Vesicoureteral Reflux is an Independent Risk Factor for Breakthrough Febrile Urinary Tract Infection

Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making.

Discrete Choice Experiment to Evaluate Factors That Influence Preferences for Antibiotic Prophylaxis in Pediatric Oncology

BackgroundBacterial and fungal infections in pediatric oncology patients cause morbidity and mortality. The clinical utility of antimicrobial prophylaxis in children is uncertain and the personal utility of these agents is disputed. Objectives were to use a discrete choice experiment to: (1) describe the importance of attributes to parents and healthcare providers when deciding between use and non-use of antibacterial and antifungal prophylaxis; and (2) estimate willingness-to-pay for prophylactic strategies.MethodsAttributes were chances of infection, death and side effects, route of administration and cost of pharmacotherapy. Respondents were randomized to a discrete choice experiment outlining hypothetical treatment options to prevent antibacterial or antifungal infections. Each respondent was presented 16 choice tasks and was asked to choose between two unlabeled treatment options and an opt-out alternative (no prophylaxis).Results102 parents and 60 healthcare providers participated. For the antibacterial discrete choice experiment, frequency of administration was significantly associated with utility for parents but not for healthcare providers. Increasing chances of infection, death, side effects and cost were all significantly associated with decreased utility for parents and healthcare providers in both the antibacterial and antifungal discrete choice experiment. Parental willingness-to-pay was higher than healthcare providers for both strategies.ConclusionChances of infection, death, side effects and costs were all significantly associated with utility. Parents have higher willingness-to-pay for these strategies compared with healthcare providers. This knowledge can help to develop prophylaxis programs.

Lack of benefit of preoperative antimicrobial prophylaxis in children with acute appendicitis: a prospective cohort study

Preoperative antimicrobial prophylaxis is widely used in pediatric patients undergoing appendectomy, but evidence showing a reduction of postoperative infectious complications is lacking. A prospective consecutive cohort study on changing from preoperative antimicrobial prophylaxis to no prophylaxis in children undergoing urgent appendectomy was undertaken. The impact of this change in management on postoperative infectious complications was evaluated by comparing the outcome in 100 patients receiving (group A) and a subsequent 100 patients not receiving prophylaxis (group B), which consisted of a preoperative single dose of intravenous metronidazole (10 mg/kg body weight). Histology confirmed acute appendicitis in 92 patients of group A and 95 patients of group B. In patients with histological simple appendicitis, postoperative infectious complications were noted in 2 (3.0 %) of 69 patients from group A and in none of 70 patients from group B, and in patients with histological perforated appendicitis in 5 (22 %) of 23 and 4 (16 %) of 25 patients from groups A and B, respectively. Postoperative infectious complications were more frequent (p < 0.05) in perforated than in simple appendicitis. These infectious complications included in simple appendicitis two wound infections in group A, and in perforated appendicitis four intraabdominal abscesses and one wound infection in group A and two intraabdominal abscesses and two wound infections in group B. Postoperative infectious complications were seen more often in patients with perforated appendicitis than in those with simple appendicitis. Preoperative antimicrobial prophylaxis with metronidazole did not reduce the rates of postoperative infectious complications.

Antibiotic prophylaxis and the prevention of surgical site infection

Surgical site infection (SSI) is one of the most common complications of surgery in both adults and children. The purpose of the present review is to highlight the progress in the understanding of SSIs and the current role of antimicrobial prophylaxis (AMP). An SSI is diagnosed by a constellation of clinical findings occurring within 30 days of surgery. Pathologic organisms responsible for the development of an SSI are mainly limited to Gram-positive bacteria. Two well documented risk factors for the development of SSI in children are wound classification by the Centers for Disease Control (CDC) and procedure duration. Administration of appropriate AMP prior to skin incision has been shown to reduce the incidence of SSI in selected procedures. However, there is a lack of consensus on which procedures in children require AMP. Improvement in the perioperative care of children has reduced both the incidence and outcomes of SSI. However, several controversies still exist in the use of AMP in children. Future work by pediatricians, pediatric surgeons, and pediatric infectious disease specialists will enable us to better understand the specific indications and appropriate AMP in children.

Antimicrobial prophylaxis in children with recurrent urinary tract infections

Antimicrobial prophylaxis in children with recurrent urinary tract infections

Recurrent Urinary Tract Infections in Children

The evidence regarding risk factors for recurrent urinary tract infection (UTI) and the risks and benefits of antimicrobial prophylaxis in children is scant. To identify risk factors for recurrent UTI in a pediatric primary care cohort, to determine the association between antimicrobial prophylaxis and recurrent UTI, and to identify the risk factors for resistance among recurrent UTIs. From a network of 27 primary care pediatric practices in urban, suburban, and semirural areas spanning 3 states, a cohort of children aged 6 years or younger who were diagnosed with first UTI between July 1, 2001, and May 31, 2006, was assembled. Time-to-event analysis was used to determine risk factors for recurrent UTI and the association between antimicrobial prophylaxis and recurrent UTI, and a nested case-control study was performed among children with recurrent UTI to identify risk factors for resistant infections. Time to recurrent UTI and antimicrobial resistance of recurrent UTI pathogens. Among 74 974 children in the network, 611 (0.007 per person-year) had a first UTI and 83 (0.12 per person-year after first UTI) had a recurrent UTI. In multivariable Cox time-to-event models, factors associated with increased risk of recurrent UTI included white race (0.17 per person-year; hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.22-3.16), age 3 to 4 years (0.22 per person-year; HR, 2.75; 95% CI, 1.37-5.51), age 4 to 5 years (0.19 per person-year; HR, 2.47; 95% CI, 1.19-5.12), and grade 4 to 5 vesicoureteral reflux (0.60 per person-year; HR, 4.38; 95% CI, 1.26-15.29). Sex and grade 1 to 3 vesicoureteral reflux were not associated with risk of recurrence. Antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI (HR, 1.01; 95% CI, 0.50-2.02), even after adjusting for propensity to receive prophylaxis, but was a risk factor for antibimicrobial resistance among children with recurrent UTI (HR, 7.50; 95% CI, 1.60-35.17). Among the children in this study, antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI, but was associated with increased risk of resistant infections.

Antimicrobial Prophylaxis in Children with HIV Infection

Pediatric AIDS Clinical Trials Group describing a randomized comparison of daily administration of trimethoprim-sulfamethoxazole (TMP-SMZ) and atovaquone-azithromycin brings into focus a number of interesting issues related to HIV infections worldwide as well as the daily use of prophylactic antimicrobials in general. The trial was halted early before it was fully accrued and perhaps as a result of this it failed to achieve statistical significance for its central comparisons. However in spite of this early discontinuation the trial teaches us a few important lessons. Hughes and colleagues’ own landmark placebo-controlled randomized clinical trial that compared daily doses of TMP-SMZ with placebo in children with cancer and leukemia showed clearly in 1977 that not only was Pneumocystis jiroveci (formerly “carinii”) pneumonia (PCP) almost completely prevented but the numbers of proven and presumptive bacterial infections were also reduced significantly in this population of high-risk immunocompromised patients. In HIV infected adults very similar results were seen in a randomized comparison between aerosolized pentamidine and daily doses of TMP-SMZ published in 1992. (excerpt)

From the Centers for Disease Control and Prevention. Recommendations for antimicrobial prophylaxis for children and breastfeeding mothers and treatment of children with anthrax.

From the Centers for Disease Control and Prevention. Recommendations for antimicrobial prophylaxis for children and breastfeeding mothers and treatment of children with anthrax.

Prophylaxis for recurrent acute otitis media: a Brazilian study

We enrolled 60 children with recurrent acute otitis media (AOM) in a study of the effectiveness of antimicrobial prophylaxis. All children were entered into the study following an acute episode of infection treated with amoxacillin (AMX) for 10 days. Following therapy, the children were re-examined, and then randomly assigned to receive either trimethoprim-sulfamethoxazole (TMP-SMX), amoxacillin (AMX) or a placebo (PLA). Twenty children were included in each group. Each drug was administered once a day at bedtime, at 1/3 the therapeutic dose, for 3 months. Children were re-evaluated with pneumootoscopy during episodes of acute illness and with pneumootoscopy and impedance tympanometry (TYMP) at monthly intervals. We observed a significantly increased rate of recurrent AOM in children receiving placebo compared with those who received antibiotics (50% vs. 17% P < 0.005). Both prophylactic antibiotics were equally effective in preventing recurrent AOM (recurrence rate 20% TMP-SMX, 15% AMX). We also observed that recurrences in children receiving placebo occurred earlier in the study period than in those receiving antibiotics. These results suggest that antimicrobial prophylaxis in children with recurrent acute otitis media is effective in reducing subsequent disease. The similar efficacy of both antibiotics tested suggests that the less expensive agent should be used.

Antimicrobial Prophylaxis in Pediatric Surgical Patients

A major use of antimicrobial agents in hospitalized children is prophylaxis of postoperative wound infections. In view of this frequent use and the emerging consensus on recommendations for prevention of surgical wound infections,1 the American Academy of Pediatrics has developed guidelines for surgical antimicrobial prophylaxis in children. Prophylaxis is defined as use of antimicrobial drugs in the absence of suspected or documented infection. FREQUENCY OF ANTIMICROBIAL PROPHYLAXIS In an extensive study of patients in acute care general hospitals in Pennsylvania, 36% of antimicrobial courses were initiated for prophylaxis of infection after surgery or an invasive procedure, such as cystoscopy or cardiac catheterization.2 The prevalence and reasons for antimicrobial use have been studied primarily in general or adult hospitals, but the patterns of use in children are similar to those in adults.3-5 Two studies have demonstrated that prophylaxis accounts for approximately 75% of the antibiotic use on pediatric surgical services.4,6 The efficacy of antimicrobial prophylaxis in lowering the incidence of postoperative infection after certain types of surgery has been demonstrated amply in controlled clinical trials.7 These and earlier studies by Miles et al8 and Burke9 in experimental animals have delineated the principles for effective use of antimicrobial agents in surgical prophylaxis, including choice of drugs and when and how long they are to be given. INAPPROPRIATE ANTIMICROBIAL PROPHYLAXIS Prophylaxis has been incriminated as a major cause of inappropriate use of these antimicrobial agents in both adults and children.4,5,10-12 In 74% of antimicrobial courses given for prophylaxis in the Pennsylvania study, the duration exceeded 48 hours, an interval beyond which continuation has not been proven beneficial.2

Antimicrobial Prophylaxis for Recurrent Acute Otitis Media

Antimicrobial prophylaxis for children who have frequently recurring, severe episodes of acute otitis media appears to constitute a reasonable management option, even though it is not yet clear whether the advantages outweigh the disadvantages and risks. It remains for well-designed and well-executed studies that extend over relatively long periods to indicate whether this approach to management is the best of the available options, and if so, which of the available drugs is preferable.