Pneumonia due to unusual organisms in children

Generally antimicrobials for treatment of pneumonia are chosen to target the usual bacterial etiological agents. Such regimens are unable to cure patients of pneumonia caused by 'unusual organisms' mycoplasma, chlamydia, Pneumocystis carinii and Legionella pneumophilus). Thus, there is a need to anticipate their presence in appropriate cases and to plan the initial antimicrobial therapy accordingly. Studies in Europe as well as India have shown that such infections form a fairly substantial percentage of community acquired pneumonia in children. Mycoplasma pneumoniae and Chlamydia pneumoniae are common in school age children while Chlamydia trachomatis occurs in early infancy. Pneumocystis carinii is an important pathogen in immunocompromised children. Routine laboratory tests and radiological features are not specific enough to give accurate diagnosis of these infections for which one has to depend on sophisticated culture techniques, immunological tests for the antigens or antibodies and polymerase chain reaction. Mycoplasma, chlamydia and legionella infections respond to macrolide antibiotics and for pneumocystis infections, trimethoprim-sulfamethaxozole or pentamidine is the drug of choice. Overall prognosis with appropriate treatment is good except for P. carinii infection in immunocompromised host which carries a high mortality and recurrence rate.     

Polymerase chain reaction detection of Kingella kingae in children with culture-negative septic arthritis in eastern Ontario

BACKGROUND:

The bacterium Kingella kingae may be an under-recognized cause of septic arthritis in Canadian children because it is difficult to grow in culture and best detected using molecular methods.

OBJECTIVES:

To determine whether K kingae is present in culture-negative joint fluid specimens from children in eastern Ontario using polymerase chain reaction (PCR) detection methods.

METHODS:

K kingae PCR testing was performed using residual bacterial culture-negative joint fluid collected from 2010 to 2013 at a children’s hospital in Ottawa, Ontario. The clinical features of children with infections caused by K kingae were compared with those of children with infections caused by the ‘typical’ septic arthritis bacteria, Staphylococcus aureus and Streptococcus pyogenes.

RESULTS:

A total of 50 joint fluid specimens were submitted over the study period. Ten were culture-positive, eight for S aureus and two for S pyogenes. Residual joint fluid was available for 27 of the 40 culture-negative specimens and K kingae was detected using PCR in seven (25.93%) of these samples. Children with K kingae were significantly younger (median age 1.7 versus 11.3 years; P=0.01) and had lower C-reactive protein levels (median 23.8 mg/L versus 117.6. mg/L; P=0.01) than those infected with other bacteria.

CONCLUSIONS:

K kingae was frequently detected using PCR in culture-negative joint fluid specimens from children in eastern Ontario. K kingae PCR testing of culture-negative joint samples in children appears to be warranted.     

Role of antimicrobial applications to the umbilical cord in neonates to prevent bacterial colonization and infection: a review of the evidence

In developing countries umbilical cord infections constitute a major cause of neonatal morbidity and pose significant risk for mortality, whereas outbreaks of cord infections continue to occur in developed country nurseries. Cord infections in developing countries can be prevented through increasing access to tetanus toxoid immunization during pregnancy, promoting clean cord care and reducing harmful cord applications and behaviors. Interventions introduced in both developed and developing countries to reduce exposure of the cord to infectious pathogens include clean cord cutting, hand-washing before and after handling the baby, bathing of the infant with antimicrobial agents and application of antimicrobials to the cord. Despite the importance of umbilical cord care, both traditionally and medically, there have been few randomized trials investigating the impact of different cord care regimens on rates of local or systemic infections, particularly in developing countries.This review examines available data on umbilical cord care, with a particular focus on those comparing rates of bacterial colonization and/or rates of cord infection among neonates receiving different umbilical cord care regimens. Although most investigators agree that topical antimicrobials reduce bacterial colonization of the cord, a firm relationship between colonization and infection has not been established. Further research in developed countries, including follow-up beyond hospital discharge, is required before advising on "best cord care practices." The paucity of published reports from developing countries indicates the need to investigate the impact of antimicrobial applications on cord and systemic infections in a community-based, prospective manner.     

Sexually transmitted infections in adolescents: Maximizing opportunities for optimal care

Sexually transmitted infections are a growing public health concern in Canada, with rates of Chlamydia trachomatis infection, gonorrhea and syphilis increasing among adolescents and young adults. The present practice point outlines epidemiology, risk factors, laboratory testing and management for C trachomatis, Neisseria gonorrhoeae and Treponema pallidum, with a lesser focus on HIV. The need for test-of-cure and indications for further investigations are also discussed. The importance of maximizing opportunities to screen for and treat sexually transmitted infections in this age group is highlighted.     

Outpatient Management of Community-associated Methicillin-resistant Staphylococcus aureus Skin and Soft Tissue Infection

During the past decade, there has been a dramatic increase in the number of patients presenting with skin and soft tissue infections in the outpatient setting. The predominant causative bacterium for these infections has recently been identified as community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). It is estimated that nearly 80% of infections caused by CA-MRSA manifest as skin and soft tissue infections which are of mild to modest severity. However, invasive disease and fatal illness has been reported among otherwise healthy adults and children. The rapid evolution of CA-MRSA presents a unique challenge for pediatric health care providers. As such, it is critical to raise awareness regarding the epidemiology, microbiology, and evidence-based treatment options for treating skin and soft tissue infections in the age of CA-MRSA. The aims of this article include discussion regarding the epidemiology, microbiology, and evidence-based management of CA-MRSA as well as publication of a more relevant one-page evidence-based treatment flow diagram and antimicrobial prescribing table for health care providers practicing in the ambulatory care setting.     

Pediatric Blood Cultures and Antibiotic Resistance: An Overview

Bloodstream infections (BSI) due to multidrug-resistant organisms, especially from pediatric intensive care units (PICU), are being increasingly reported across the world. Since BSI is associated with high mortality, it is essential to treat these infections early with appropriate antibiotics. Surveillance of etiology and emerging antimicrobial resistance (AMR) is considered an important step in the formulation of antibiotic policy for early treatment and judicious use of antibiotics. In this review on etiology and its antibiogram in community acquired BSI, S. typhi followed by S. paratyphi A were the major bacterial isolates. Quinolone resistance of more than 90% in Salmonella is now reported from all over India. Ceftriaxone remains the drug of choice for enteric fever due to its 100% susceptibility. In PICU there is an emergence of candidemia due to non-albicans candida which are now predominant isolates at few centers. BSI due to gram-negative bacteria, mostly by Klebseilla pneumoniae and gram-positive cocci (S. aureus) are the other major pathogens commonly observed in BSI from PICU. There is a high prevalence of antimicrobial resistance to commonly used antibiotics like ampicillin (94.9%–90.7%), cefotaxime (92.4%–71.4%), piperacillin-tazobactum (31.2%–27.5%) and levofloxacin (42.4%–39.8%). Resistance to carbapenems, primarily due to blaNDM is seen in all the centers and the rate varies between 1%- 79% with K. pneumoniae and A. baumannii showing the maximum resistance. This review highlights the magnitude of the AMR in the pediatric population and calls for the urgent implementation of antimicrobial stewardship programs to save the remaining antimicrobials.     

Pulmonary infections and community associated methicillin resistant Staphylococcus aureus: a dangerous mix?

The incidence of complicated pneumonias in children is increasing with a concurrent increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. CA-MRSA is distinct from hospital associated MRSA [HA-MRSA] in regards to its genotype, epidemiology, and clinical course. Unlike HA-MRSA, CA-MRSA often strikes young, previously healthy children. Pneumonias caused by CA-MRSA have a rather distinct presentation. Because of its pore-forming toxins, namely Panton-Valentine leukocidin (PVL) and alpha-hemolysin, extensive necrotizing disease with corresponding hypoxaemia and hypercarbia is common. Other features include multilobar disease, leucopenia, haemoptysis, and high mortality rates. A previous influenza-like illness or skin and soft tissue infection [SSTI] often precede the development of pneumonia due to CA-MRSA. Vancomycin is recommended as first-line empiric therapy for suspected CA-MRSA infections. However, vancomycin is not an ideal agent for the treatment of pneumonia given its poor concentrating ability in alveolar fluid. Linezolid and clindamycin have also been used in the treatment of CA-MRSA pneumonia and ongoing research is looking for alternative antimicrobials. Recent studies have continued to report a lack of correlation between nasal colonization and active infections due to CA-MRSA. Given that the role of nasal colonization in CA-MRSA infection is not clear, the utility of decolonization treatment has been a point of debate. Finally, patients with cystic fibrosis are becoming increasingly colonized with MRSA as opposed to MSSA. There is some accumulating evidence that patients with MRSA show a more rapid deterioration in their degree of obstructive disease as measured by forced expiratory volume in one second (FEV₁). However, it still is not clear whether MRSA is a marker for worsening disease or whether it actually is a cause of disease progression in cystic fibrosis. More longitudinal data is needed to understand how MRSA colonization impacts the course of disease in cystic fibrosis.     

Epidemiology and clinical management of tuberculosis in children in Canada

Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed.     

Proper antibiotic therapy. From penicillin to pharmacogenomic

Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible. Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. Several study demonstrated an excessive amount of antibiotic prescribing for communities patients and inpatients and in some hospital up to 50% of antibiotic usage is inappropriate: the benefits of antibiotic treatment come with the risk of antibiotic resistance development. In hospitals, infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use. Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies. Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. These evidence-based guidelines are not a substitute for clinical judgment, and clinical discretion is always required in their application. Genome studies have identified hundreds of genetic polymorphism important determinants of the efficacy of therapy and several trial demonstrated the successful use of pharmacogenomic testing to reduce the incidence of hypersensitivity reactions in patients. Knowing the phenotype of a patient prior to therapy, optimal dose and type drugs can be prescribed to achieve better management of patients.     

Combined influence of practice guidelines and prospective audit and feedback stewardship on antimicrobial treatment of community-acquired pneumonia and empyema in children: 2012 to 2016

BackgroundAminopenicillins are recommended empiric therapy for community-acquired pneumonia (CAP). The aim of the study was to assess treatment over a 5-year period after CAP guideline publication and introduction of an antimicrobial stewardship program (ASP).MethodsUsing ICD-10 discharge codes for pneumonia, children less than 18 years admitted to the Children’s Hospital of Eastern Ontario January 1, 2012 and December 31, 2016 were identified. Children ≥ 2 months with consolidation were included. One day of therapy (DOT) was one or more doses of an antimicrobial given for 1 day.ResultsOf 1,707 patients identified, 713 met inclusion criteria. Eighteen (2.5%) had bacteria identified by culture and 79 of 265 (29.8%) had Mycoplasma pneumoniae detected. Mean DOT/1,000 patient days of aminopenicillins/penicillin (AAP) increased by 18.1% per year (95% confidence interval [CI] −0.2, 39.9%) and decreased by 37.6% per year (95% CI −56.1, −11.3%) for second- and third-generation cephalosporins in the post-ASP period. The duration of discharge antimicrobials decreased. Of 74 (10.4%) patients who had pleural fluid drained, 35 (47.3%) received more than 5 days of AAP and ≤ 5 days of second-/third-generation cephalosporins with no difference in median length of stay nor mean duration of antimicrobials.ConclusionsImplementation of CAP management guidelines followed by prospective audit and feedback stewardship was associated with a sustained decrease in the use of broad-spectrum antibiotics in childhood CAP. Use of AAP should also be strongly considered in patients with effusions (even if no pathogen is identified), as clinical outcome appears similar to patients treated with broad-spectrum antimicrobials.     

Narrow- versus broad-spectrum parenteral antimicrobials against common infections of childhood: a prospective and randomised comparison between penicillin and cefuroxime

Overuse of broad-spectrum antimicrobials has resulted in increasing bacterial resistance in many countries. We hypothesised that common childhood infections requiring parenteral medication are still curable with narrow-spectrum and inexpensive penicillin. A prospective and randomised study was performed in two referral hospitals in Helsinki. A total of 154 children aged 3 months to 15 years with pneumonia or other lower respiratory infections, sepsis-like infections, or other common acute infections warranting hospitalisation and parenteral antimicrobials were included. At random, 50% of children received procaine penicillin intramuscularly, the other 50% cefuroxime intravenously for 4–7 days. The course of illness was monitored with predetermined laboratory and radiological indices, by filling in a special form daily and a follow-up for 30 days after discharge. The infectious agent was searched for with a large laboratory set-up covering 23 bacterial, viral or protozoan species. The two groups were very similar at presentation. Probable aetiology was disclosed in 56% of the penicillin and in 68% of the cefuroxime recipients, the leading agent in both groups being Pneumococcus. In 8% only a viral aetiology was found. The children recovered with the same speed, regardless of which antimicrobial used, there being one possible failure in each group but no difference in the frequency of needing a physician again within 1 month of discharge. No adverse event was attributable to either drug. Conclusion Procaine penicillin is as effective and safe as cefuroxime for common community-acquired infections in immunocompetent children. Received: 1 May 1999 / Accepted: 22 May 2000     

Surveillance of antibiotic therapy in a pediatric intensive care unit]

Since 1982, a pediatric intensive care unit for neonates and pediatric patients up to 15 years of age has prospectively recorded every instance of use of antimicrobials, with the reasons for use, clinical and bacteriological parameters, and outcome. This approach encourages strict adherence to established protocols and provides a basis for discussing the rationale of each antimicrobial course. Effectiveness of protocols is evaluated annually and modifications or additions are introduced, as appropriate. Patterns in the proportion and nature of antimicrobials used to treat hospital-acquired infections can be monitored on the basis of the data collected. Changes in the nature of antimicrobials used, which may have repercussions on pathogen resistance to antimicrobials, are also monitored. Reasons for use of antimicrobials are categorized as follows: A = primary infection: B = secondary infection acquired in the ICU; C: secondary infection acquired in another unit or in another hospital; D = prophylaxis. In 1987, 46% of neonates and 59% of patients above one month of age were given antimicrobial agents; these figures are similar to those recorded during the previous years. Reasons for antimicrobial therapy were as follows in neonates: A = 48.5%; B = 40%; C = 1.2%; D = 10.3%; in patients above one month of age corresponding figures were: A = 23%; B = 44%; C = 0.9%; D = 31.9%. Among the neonates, the ampicillin-aminoglycoside combinations accounted for 41.5% of treatments (1/4th of these treatments were continued); in the older patients, penicillin G and ampicillin were the most commonly used antibiotics. In all age groups, hospital-acquired infections were mainly respiratory tract infections (approximately 50% in neonates and 80% in patients above one month of age). Staphylococcus aureus was the most prevalent organism; Pseudomonas was seen virtually only among the patients above one month of age with very prolonged endotracheal intubation. From 1983 through 1987, use of third-generation cephalosporins increased from 4.5% to 28.3% in neonates and from 5.5% to 9% for patients above one month of age. The changes identified over time should be interpreted in the light of changing patterns of disease; in particular, hospital-acquired infections among neonates increased twofold, probably as a result of the rising number of very-low-birth-weight infants.     

Community-acquired lobar pneumonia in children in the era of universal 7-valent pneumococcal vaccination: a review of clinical presentations and antimicrobial treatment from a Canadian pediatric hospital

ABSTRACT: BACKGROUND: Community-acquired pneumonia (CAP) is a common cause of pediatric admission to hospital. The objectives of this study were twofold: 1) to describe the clinical characteristics of CAP in children admitted to a tertiary care pediatric hospital in the pneumococcal vaccination era and, 2) to examine the antimicrobial selection in hospital and on discharge. METHODS: A retrospective review of healthy immunocompetent children admitted to a tertiary pediatric hospital from January 2007 to December 2008 with clinical features consistent with pneumonia and a radiographically-confirmed consolidation was performed. Clinical, microbiological and antimicrobial data were collected. RESULTS: One hundred and thirty-five hospitalized children with pneumonia were evaluated. Mean age at admission was 4.8 years (range 0--17 years). Two thirds of patients had been seen by a physician in the 24 hours prior to presentation; 56 (41.5%) were on antimicrobials at admission. 52 (38.5%) of patients developed an effusion, and 22/52 (42.3%) had pleural fluid sampled. Of 117 children who had specimens (blood/pleural fluid) cultured, 9 (7.7%) had pathogens identified (7 Streptococcus pneumoniae, 1 Group A Streptococcus, and 1 Rhodococcus). 55% of patients received 2 or more antimicrobials in hospital. Cephalosporins were given to 130 patients (96.1%) in hospital. Only 21/126 patients (16.7%) were discharged on amoxicillin. The median length of stay was 3 days (IQR 2--4) for those without effusion and 9 (IQR 5--13) for those with effusion. No deaths were related to pneumonia. CONCLUSIONS: This study provides comprehensive data on the clinical characteristics of hospitalized children with CAP in the pneumococcal 7-valent vaccine era. Empiric antimicrobial choice at our institution is variable, highlighting a need for heightened antimicrobial stewardship.     

Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran

Background:

Helicobacter pylori infects around 50% of the human population and is asymptomatic in 70% of the cases. H. pylori eradication in childhood will not only result in peptic symptoms relief, but will also prevent late-term complications such as cancer. Today, probiotics are being increasingly studied in the treatment of gastrointestinal infections as an alternative or complement to antibiotics.

Objectives:

In this study we aimed to assess the effect of S. boulardii supplementation on H. pylori eradication among children in our region.

Patients and Methods:

In this randomized double-blind placebo-controlled clinical trial 28 asymptomatic primary school children with a positive H. pylori stool antigen (HpSA) exam were randomly allocated into the study group, receiving Saccharomyces boulardii, and the control group receiving placebo capsules matched by shape and size, for one month. The children were followed up weekly and were reinvestigated four to eight weeks after accomplished treatment by HpSA testing. The significance level was set at P < 0.05.

Results:

24 children completed the study. The mean HpSA reduced from 0.40 ± 0.32 to 0.21 ± 0.27 in the study group, indicating a significant difference (P = 0.005). However, such difference was not observed in the control group (P = 0.89). Moreover, the HpSA titer showed a 0.019 ± 0.19 decrease in the study group whereas the same value was 0.0048 ± 0.12 for the controls, again stating a significant difference (P = 0.01).

Conclusions:

Saccharomyces boulardii has a positive effect on reducing the colonization of H. pylori in the human gastrointestinal system but is not capable of its eradication when used as single therapy.     

Duration of symptoms and outcome in bacterial meningitis: an analysis of causation and the implications of a delay in diagnosis.

The prompt diagnosis and therapy of bacterial meningitis remain enduring clinical challenges, for no physician would knowingly delay appropriate therapy. However, whether a delay in the initiation of antimicrobials in fact causes a worse outcome is a separate and tangential question. In clinical medicine a treatment decision involves a bedside estimate of the risk and potential severity of illness balanced against the benefits and adverse effects of therapy. For severe infections, the inexorable damage of untreated disease is presumed, and antimicrobials properly are given without hesitation. In contrast the methodical weighing of evidence regarding the issue of causation is for the purpose of characterizing biologic phenomena. Although legal and medical implications may be contained in such an analysis, its relevance to any particular clinical case is only retrospective. To judge responsibly the strength of a causative link, all available scientific evidence must be analyzed by established criteria. Such as analysis suggests that any connection between a delay in the treatment of bacterial meningitis and outcome depends on the presenting clinical pattern. If the presentation is that of a nonspecific illness with general symptoms, then a short delay of < 3 to 5 days does not appear to alter the risk of sequelae or death. In the case of fulminant meningitis a delay in initiating therapy seems unconnected to outcome. Finally for patients with a history of clinically overt meningitis, an inappropriate delay in commencing therapy incrementally increases the risk of permanent injury.     

新生儿耐碳青霉烯类肠杆菌感染的防治

碳青霉烯类耐药已经逐渐成为中国新生儿重症监护室面临的严峻问题。耐碳青霉烯类肠杆菌(carbapenem-resistant enterobacteriaceae,CRE)通过产生碳青霉烯酶,水解包括碳青霉烯类在内的绝大部分β-内酰胺类抗生素,具有高度的耐药性。碳青霉烯酶根据Amber分类可分为A、B、D三类,不同碳青霉...     

Antimicrobial Chemotherapy for Children with Malignancy

Infection is the major complication occurring in children with cancer and is often fatal. Since the clinical manifestations of infection are slight, except for fever, a definitive diagnosis is difficult in the early phase of infection, but using laboratory parameters, the differentiation of bacterial infections may be possible to some extent. The infection cannot be treated only by antimicrobial chemotherapy, but supportive measures such as neutrophil transfusion, and other biological medications should be given in consideration of the deficiency of the immune defense mechanisms of the patient. Anticancer treatment is also needed, along with antimicrobial treatment. The prophylactic use of antimicrobial drugs is still controversial but it is effective, depending on the type of infection for which it is used, and on the status of the defective defense mechanism in the patient who is on cancer chemotherapy.     

Staphylococcus aureus bloodstream infections in children: A population-based assessment

BACKGROUND:

Although Staphylococcus aureus is a major cause of bloodstream infections, population-based data on these infections in children are limited.

OBJECTIVE:

To describe the epidemiology of S aureus bacteremia in children.

METHODS:

Population-based surveillance for all incident S aureus bacteremias was conducted among children (18 years of age or younger) living in the Calgary Health Region (Alberta) from 2000 to 2006.

RESULTS:

During the seven-year study, 120 S aureus bloodstream infections occurred among 119 patients; 27% were nosocomial, 18% health care associated and 56% community acquired. The annual incidence was 6.5/100,000 population and 0.094/1000 live births. A total of 52% had a significant underlying condition, and this was higher for nosocomial cases. Bone and joint (40%), bacteremia without a focus (33%), and skin and soft tissue infections (15%) were the most common clinical syndromes. Infections due to methicillin-resistant S aureus were uncommon (occurring in one infection) and three patients (2.5%) died.

CONCLUSIONS:

S aureus bacteremia is an important cause of morbidity in the paediatric age group. Underlying medical conditions and implanted devices are important risk factors. Methicillin-resistant S aureus and mortality rates are low.     

新生儿抗生素合理使用研究进展

抗生素是新生儿重症监护病房（NICU）的常用药物。然而,在生后早期,不必要地或长时间地暴露于抗生素,可增加新生儿发生不良预后的风险。NICU中的抗生素治疗大多始于经验性治疗。新生儿经验性抗生素治疗的启动标准及治疗疗程尚不统一。针对细菌培养阴性且临床表现稳定的新生儿,及时终止经验性抗生素治疗已成为共识。目前NICU中抗生素的使用存在较大差异。采取针对性的抗生素管理措施,是优化NICU抗生素使用方案的有效途径。