Use of Cefoperazone/sulbactam in neonates

Background: Neonates are at high risk for nosocomial infections due to multidrug‐resistant pathogens. The use of β‐lactamase inhibitors in combination with β‐lactam antibiotics broadens the antimicrobial spectrum. Cefoperazone/sulbactam is used in children but there are limited data on its usage in neonates. The purpose of the present study was therefore to evaluate the use of cefoperazone/sulbactam in the treatment of neonatal infections caused by multidrug‐resistant pathogens. Methods: The records of neonates who were hospitalized and who received cefoperazone/sulbactam were reviewed. Results: There were 90 infants who received cefoperazone/sulbactam. A pathogen could be isolated in 41 (45.6%) of the infants. In total, 17.1% of isolated pathogens were resistant to cefoperazone/sulbactam. Side‐effects were seen in four of the infants. Two infants had cholestasis, one infant had neutropenia and one had superinfection with candida. Conclusion: Cefoperazone/sulbactam can be used in the treatment of nosocomial infections caused by multidrug‐resistant pathogens in neonates.     

Colistin administration to pediatric and neonatal patients

Emergence of multidrug-resistant Gram-negative nosocomial pathogens has led to resurgence of colistin use. Safety and efficacy data regarding colistin use in pediatric patients are sparse, while optimal dosage has not been defined. We present a case series of neonates and children without cystic fibrosis treated with various doses of colistin intravenously. The records of patients who received colistin in a tertiary-care hospital from January 2007 to March 2009 were reviewed. Thirteen patients (median age 5 years, range 22 days to 14 years) received 19 courses of colistin as treatment of pneumonia, central nervous system infection, bacteremia, or complicated soft tissue infection. The isolated pathogens were Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Daily dose of colistin (colistimethate) ranged between 40,000 and 225,000 IU/kg. Duration of administration ranged from 1 to 133 days. Other antimicrobials were co-administered in 18/19 courses. Increase of serum creatinine in one patient was associated with co-administration of colistin and gentamicin. Sixteen of 19 courses had a favorable outcome, and only two of the three deaths were infection-related. Colistin intravenous administration appears well tolerated even at higher than previously recommended doses and of prolonged duration.     

Outcome of ventilator-associated pneumonia due to multidrug-resistant <Emphasis Type="Italic">Acinetobacter baumannii</Emphasis> and <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> treated with aerosolized colistin in neonates: a retrospective chart review

Multidrug-resistant (MDR) gram-negative bacteria-related nosocomial infections and ventilator-associated pneumonia (VAP) presents an emerging challenge to clinicians. Older antimicrobial agents such as colistin have become life-saving drugs because of the susceptibility of these pathogens. We report our experience with aerosolized colistin in two preterm and one term neonate with Acinetobacter baumannii and Pseudomonas aeruginosa-related VAP who were unresponsiveness to previous antimicrobial treatment. All pathogens were isolated from tracheal aspirate. We used 5 mg/kg (base activity) aerosolized colistin methanesulfonate sodium in every 12 h as an adjunctive therapy for VAP. VAP was treated by 14, 14, and 16-day courses of aerosolized colistin in these patients, respectively. No adverse effect such as nephrotoxicity or neurotoxicity was observed. We found that aerosolized colistin was tolerable and safe, and it may be an adjunctive treatment option for MDR gram-negative bacterial VAP in neonates. Further studies are needed to determine appropriate doses for aerosolized colistin and its eligibility as an alternative treatment choice in newborns.     

Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year prospective study

Aim: Investigate the incidence, etiological pattern and the antimicrobial resistance of late‐onset neonatal infections over a period of 5 years. Methods: Longitudinal audit of neonatal sepsis from January 2005 to December 2009, in the main maternity hospital in Kuwait. Late‐onset neonatal infection was defined as the culture of a single potentially pathogenic organism from blood or cerebrospinal fluid from an infant older than 6 days in association with clinical or laboratory findings consistent with infection. Results: The overall incidence was 16.9 (95% confidence interval: 15.8–18.0) episodes per 1000 live births. The commonest pathogen was coagulase‐negative Staphylococcus, 339 (35.7%), while Klebsiella was the most common gram‐negative infection, 178 (18.8%). Escherichia coli, Enterococcus and Enterobacter spp were each responsible for 6% of all infections. Candida caused 104 (11.0%) infections. The general pattern of infection remained unchanged over the study period. Case fatality was 11.7% (95% confidence interval: 9.7–13.9%) and was high for Pseudomonas (18.4%) and Candida (22.1%) infections. Approximately 24 and 20% of Klebsiella infections were resistant to cefotaxime and gentamicin, respectively, while 28 and 24% of Escherichia coli infections were resistant to cefotaxime and gentamicin, respectively. Conclusion: The incidence of late‐onset infection in Kuwait is high, resembling that in resource‐poor countries. The high incidence coupled with low case fatality provides an example for settings where tertiary care is introduced without strict measures against nosocomial infections. Prevention against nosocomial infections in neonatal units has the potential to further reduce neonatal mortality in these settings.     

Clinical and molecular microbiological characteristics of carbapenem‐resistant Acinetobacter baumannii strains in an NICU

Background: Seventeen cases of Acinetobacter baumannii infection in a neonatal intensive care unit (NICU) were evaluated. The strains were characterized as resistant to carbapenems. The aim of the present study was therefore to investigate the clinical and molecular epidemiological characteristics of the 17 carbapenem‐resistant A. baumannii strains. Methods: Samples were isolated from blood or sputum from the patients in the NICU, cultured using conventional techniques and an automated system. Multiplex polymerase chain reaction (PCR) was used to detect blaOXA‐51‐like, blaOXA‐23‐like, OXA‐24, OXA‐58 and Ambler class B carbapenemases. The genotype of the strains was identified on pulsed‐field gel electrophoresis (PFGE). Results: BlaOXA‐23 was detected in all of the isolates. PFGE genotype analysis suggested three clones among the 17 strains. Two clones were isolated from other wards of the hospital including the adult ICU and Department of Pulmonology. The other clone was proved to be the first appearance in the hospital as genotype analysis. Conclusion: BlaOXA‐23 was the drug‐resistant gene that made A. baumannii resistant to carbepenem. The source of blaOXA‐23 in the 17 isolates was different.     

Risk factors and pathogen profile of ventilator‐associated pneumonia in a neonatal intensive care unit in China

Background: The aim of the present study was to explore the incidence and risk factors of, and summarize the involved pathogens in, neonates with ventilator‐associated pneumonia (VAP) in the authors' neonatal intensive care unit (NICU) to determine the effective strategies for prevention. Methods: A retrospective case–control study including 117 VAP patients and 232 controls was conducted from January 2002 to July 2008. The antibiotics sensitivity spectrum was determined on quantitative microbiological evaluation. Multiple logistic regression and Cox model analysis were performed to determine independent and accumulative risk factors for VAP. Results: Multivariate analysis showed that birthweight, mechanical ventilation (MV), parenteral alimentation, dexamethasone and other respiratory disease were associated with the development of VAP. The cumulative risk for developing VAP increased over the duration of stay in the NICU. The most common isolated bacteria of the pathogen spectrum in VAP were Klebsiella spp. (33/146), Acinetobacter baumannii (26/146), Pseudomonas aeruginosa (18/146) and Staphylococcus aureus(13/146). Meanwhile, we found that previous use of antibiotics before VAP diagnosis was not associated with the onset of VAP. Conclusions: The daily risk for VAP increases with duration of stay in the NICU after ventilation. Drug‐resistant bacteria are common pathogens for neonatal VAP in the authors' NICU.     

Nosocomial Infections and Multidrug-Resistant Bacterial Organisms in the Pediatric Intensive Care Unit

Nosocomial infections in Pediatric Intensive Care Units (PICUs) caused by multidrug-resistant bacterial organisms are increasing. This review attempts to report on significant findings in the current literature related to nosocomial infections in PICU settings with an international perspective. The types of nosocomial infections are addressed, including catheter-related bloodstream infections, ventilator-associated pneumonia, urinary tract infections, gastrointestinal infections and post-surgical wound infections. A review of emerging resistant bacterial pathogens includes methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus sp., Clostridium difficile, extended-spectrum β-lactamase producing Gram-negative organisms, Klebsiella pneumoniae carbapenemase-producing strains and multi-drug resistant Acinetobacter baumannii. Basic and enhanced infection control methods for the management and control of multidrug-resistant organisms are also summarized with an emphasis on prevention.     

Primary antimicrobial resistance of Helicobacter pylori in children during the past 9 years

Background: Antimicrobial resistance of Helicobacter pylori is a growing problem in clinical practice, particularly clarithromycin resistance. The aim of the present study was therefore to investigate the prevalence of H. pylori resistance to antimicrobial agents in Japanese children. Methods: A total of 61 H. pylori strains isolated from children (mean age, 12.6 years; range, 4–18 years) between 1999 and 2007 were studied for primary antimicrobial resistance, using a microdilution method. In addition, the eradication rate with lansoprazole‐based triple regimens was determined. Results: The overall resistance rate of clarithromycin, amoxicillin and metronidazole was 36.1%, 0% and 14.8%, respectively. Resistance to both clarithromycin and metronidazole was detected in 6.6% of the strains. The rate of clarithromycin‐resistant strains was 32.4% from 1999 to 2002 and 40.7% from 2003 to 2007, and clarithromycin minimum inhibitory concentration at which 90% of the isolates were inhibited (MIC₉₀) increased fourfold from 1999–2002 to 2003–2007, with all clarithromycin‐resistant strains showing low‐level resistance. Metronidazole resistance rates were not different between these two study periods. Regimens involving amoxicillin and clarithromycin (n= 49) had a higher eradication rate in clarithromycin‐susceptible strains (97.1%) than in the resistant strains (57.1%; P < 0.001). There was no difference in the eradication rate between 7 day and 10 or 14 day courses of the regimens (P= 0.53). The regimen with amoxicillin and metronidazole produced successful eradication in all nine patients with clarithromycin‐resistant strains. Conclusions: Clarithromycin resistance of H. pylori is high, and triple regimen treatment containing clarithromycin should be decided based on susceptibility to the agent.     

Prospective population-based study of viral lower respiratory tract infections in children under 3 years of age (the PRI.DE study)

Population-based incidence data from Europe on the disease burden of lower respiratory tract infections (LRTI) due to respiratory syncytial viruses (RSV), parainfluenza viruses (PIV) and influenzaviruses (IV) are lacking, especially with respect to the disease burden. In a 2-year prospective multicentre study of children aged <3 years in Germany, we registered population-based cases as outpatients (n=2386), inpatients (n=2924), and nosocomially-acquired (n=141). Nasopharyngeal secretions were tested for viral RNA. The annual incidence for physician visits per 100 children for all LRTI was 28.7, RSV 7.7, PIV 3.8 and IV 1.1. Annual hospitalisation rates per 10⁵ children were for all LRTI 2941, RSV 1117, PIV 261 and IV 123. Annual nosocomial cases per 10⁵ hospital days were for all LRTI 79, RSV 29, PIV 9 and IV 1.5. All five children (0.27%) who died had an underlying disease and four were nosocomially acquired. Conclusion: Hospitalisation rates due to lower respiratory tract infections in healthy children were similar to those reported elsewhere; the rates for outpatient visits were approximately ten times higher.     

Antimicrobial Chemotheraphy of Infections due to Pseudomonas aeruginosa

Aminoglycosides, β-lactam antibiotics such as piperacillin, ticarcillin and mezlocillin, and cefoperazone, cefsulodin and ceftazidime, and imipenem have excellent antipseudomonal activity and have proved useful for the control of Pseudomonas aeruginosa infections. These infections include septicemia, meningitis, pneumonia, urinary tract infection, skin and soft tissue infection and postoperative infection. The aminoglycosides are notable for their synergistic activity with β-lactams, but serum concentrations of aminoglycosides must be carefully monitored to avoid nephrotoxic and ototoxic side effects. Cross-resistance also poses special problems among the aminoglycosides, but amikacin and some dibecacin derivatives are potently active against organisms resistant to other aminoglycosides. Carbenicillin and sulbenicillin are usually given in massive dose because their MICs are high, and this can be detrimental to patients with salt intolerance. Fosfomycin also has a high sodium content. Among the cephalosporins, cefoperazone is expecially effective against biliary tract infection; ceftazidime and cefsulodin are active against Pseudomonas aeruginosa resistant to aminoglycosides. This paper summarizes the antipseudomonal activities of various Kinds of antibiotics and discusses some problems in the actual chemotherapy of Pseudomonas aeruginosa infections.     

Clinical characteristics of neonates With VACTERL association

Background: The VACTERL association (VA) is the non‐random co‐occurrence of vertebral anomalies, anal atresia, cardiovascular malformations, tracheoesophageal fistula and/or esophageal atresia, renal anomalies, and/or limb anomalies, and is referred to by the first letters of its components. Studies investigating the clinical characteristics of VA patients and probing of the observed current six component types are limited, and none of them is focused on neonates. We investigated the clinical characteristics of our patients diagnosed as having VA in the newborn period. Methods: We retrospectively reviewed the neonates whose final diagnosis was VACTERL association. Presence of at least three components of previously reported six anomalies was accepted as VACTERL association. Sex, birthweight, gestational age, postnatal age, anomalies of the systems that are included in VA, and the other features were recorded. Results: There was a male predominance (14/11) of 28 patients; and there were three patients with ambiguous genitalia. The most common observed VACTERL component was vertebral anomalies (n= 26), followed by anal atresia (n= 19), tracheoesophageal fistula/esophageal atresia (n= 17), renal anomalies (n= 15), limb anomalies (n= 15) and cardiac anomalies (n= 14). The most frequent combination was VCTL (n= 4). Fifteen (57%) patients had non‐VACTERL anomalies and the most frequent of these was ambiguous genitalia (n= 3). Conclusion: VA patients may have different clinical characteristics in different populations, and clinicians may miss some component features if the patients are evaluated after the neonatal period.     

Predictive familial risk factors and pharmacological responses in ADHD with comorbid disruptive behavior disorders

Background: The aim of the present study was to examine the putative familial risk factors and evaluate the pharmacological effects in children and adolescents of attention‐deficit–hyperactivity disorder (ADHD) with comorbid disruptive behavior disorders (DBD) and normal IQ. Methods: The retrospective study included 144 Japanese subjects (age, 5–18 years) with ADHD, of whom 35 subjects (24%) met the diagnostic criteria for DBD. Using multiple regression analysis, the familial background risk factors that might increase any comorbid antisocial behaviors were assessed. Furthermore, the 20 methylphenidate (MPH)‐resistant DBD subjects were divided into three treatment groups: MPH plus risperidone (n= 8); MPH plus carbamazepine (n= 5); and MPH plus lithium carbonate (n= 4). The effectiveness of the treatment was evaluated both before and after the add‐on therapy using the Clinical Global Impressions–Improvement (CGI‐I) and CGI‐Severity (CGI‐S) scale. Results: The putative familial risk factors were child abuse (odds ratio [OR], 19.48; P= 0.013) and maternal psychiatric disorders (OR, 15.59; P= 0.027). The addition of risperidone had the strongest tendency to improve the CGI‐S score (P= 0.063) and the highest rate of responses (50%) among the three treatment groups, albeit with no significant differences. Very few remarkable adverse clinical symptoms were observed. Conclusions: Child abuse and maternal psychiatric disorders are suggested to be significant risk factors in influencing the development of comorbid DBD in offspring. The use of risperidone appears to be well tolerated and is moderately effective in MPH‐resistant aggression in ADHD children and adolescents with comorbid DBD.     

Rothia mucilaginosa bacteremia: A 10‐year experience of a pediatric tertiary care cancer center

Rothia mucilaginosa is part of the oral and upper respiratory tract flora. Usually, this gram‐positive coccus is not pathogenic; however, in the setting of immunosuppressed hosts, it can cause life‐threatening infections as an opportunistic pathogen. Among a cohort of 1511 hematologic‐oncologic patients at a pediatric tertiary care cancer center, we identified five cancer patients (0.35%) within a period of 10 years having a proven Rothia mucilaginosa bacteremia (1 culture positive: n = 3/5; > 1 culture positive: n = 2/5). With prompt and adequate antibiotic treatment, infection resolved rapidly before recovery of neutrophils and without any sequelae, suggesting that Rothia mucilaginosa bacteremia without organ involvement is not exceptionally problematic in pediatric cancer patients.     

Influence of smoking on human milk tumor necrosis factor‐α, interleukin‐1β, and soluble vascular cell adhesion molecule‐1 levels at postpartum seventh day

Background: The aim of this study was to investigate the effect of maternal smoking during pregnancy on human milk interleukin‐1β, tumor necrosis factor‐α (TNF‐α) and soluble vascular cell adhesion molecule‐1 levels at the postpartum seventh day. Methods: Forty‐four mothers (age range: 21–34 years) were enrolled in the study. Mothers were interviewed and classified according to their smoking status into one of two groups: the smoking mothers (n= 21) and the nonsmoking mothers (n= 23). Results: There were no significant differences between study groups with respect to human milk interleukin‐1β (P= 0.12) and soluble vascular cell adhesion molecule‐1 levels (P= 0.83). However, TNF‐α levels were found to be significantly lower in the smoking mothers compared with the controls (P= 0.002). Conclusion: This study shows that maternal smoking during pregnancy affects the levels of TNF‐α in milk. The protective effect of human milk against infections seems to be impaired in smoking mothers.     

Oophorectomy in children. Who and why: 13-year experience in a single centre

Aim: Oophorectomy performed in children is extremely uncommon. We aimed to investigate the disease pattern and the association between the underlying pathology and the clinical presentation among those patients who had their ovaries removed in their childhood. Methods: A retrospective study was performed on 41 consecutive children who underwent oophorectomy in a tertiary referral centre in the period between June 1995 and May 2008. Results: The median age was 11 years, ranged from 11 weeks to 15 years at the time of surgery. The primary presentations were acute lower abdominal pain (n= 20), progressive abdominal distension or abdominal mass (n= 13), chronic abdominal pain (n= 3), irregular menses (n= 1), antenatal diagnosis (n= 3) and incidental finding (n= 1). Ultrasound examination was performed in 31 patients and positive findings of ovarian pathology were found in all but one examination. Twenty cases of ovarian torsion were confirmed intra‐operatively. Patients presenting with acute abdominal pain were more likely to have torsion than other presentations (P < 0.01). Non‐neoplastic conditions and ovarian neoplasms were found in 11 and 30 patients, respectively. The most common neoplasm was mature teratoma (52%). Malignant neoplasms included immature teratoma (n= 3), dysgerminoma (n= 1), mixed dysgerminoma + yolk sac tumour (n= 2), yolk sac tumour (n= 2) and juvenile granulose cell tumour (n= 1). Malignant neoplasms were found to have more chronic presentation and less torsion than benign pathologies (P < 0.05). Conclusion: Although ovarian pathology is uncommon in children, a girl presenting with acute lower abdominal pain or progressive abdominal distension should raise the suspicion and prompt immediate investigation to rule out ovarian torsion or ovarian neoplasms.     

Incidence,risk factors,and outcome of blood stream infections during the first 100 days post‐pediatric allogeneic and autologous hematopoietic stem cell transplantations

Bloodstream infections (BSI) are a frequently observed complication after hematopoietic stem cell transplant (HSCT). Retrospective analysis of clinical and microbiological data during the first 100 days from 302 consecutive pediatric patients who underwent HSCT for a malignant disease at our institute between January 2013 and June 2017. A total of 164 patients underwent autologous and 138 allogeneic HSCT. The overall incidence of BSI was 37% with 92% of infectious episodes occurring during the pre‐engraftment phase. Gram‐positive bacteria (GPB) accounted for 54.6% of the isolated pathogens, gram‐negative bacteria (GNB) for 43.9%, and fungi for 1.4%. Coagulase‐negative staphylococci and Escherichia coli were the most commonly isolated GPB and GNB, respectively. Forty‐five percent of GNB were extended‐spectrum beta‐lactamase producers and 21% were multidrug‐resistant organisms. Fluoroquinolone resistance was 92% and 68%, among GPB and GNB, respectively. Risk factors for BSI in univariate analysis were allogeneic HSCT, delayed time to engraftment more than 12 days, previous BSI before HSCT, and alternative donor. In multivariate analysis, only HSCT type (allogeneic vs autologous P = .03) and previous BSI within 6 months before HSCT (P = .016) were significant. Overall survival at day 100 was 98% and did not differ significantly between patients with and without BSI (P = .76). BSI is common in children undergoing HSCT for malignant diseases. Allogeneic HSCT recipients and previous BSI within 6 months before HSCT are associated with increased risk of post‐transplant BSI. With current supportive measures, BSI does not seem to confer an increased risk for 100‐day mortality.     

The complement component C4 in sudden infant death

The aim of the present study was to compare partial deletions of the complement C4 gene in victims of totally unexplained sudden infant death (SID) (n = 89) and borderline SID (n = 15) with and without slight infections prior to death, in cases of infectious death (n = 19), and in living infants with and without infections (n = 84). The SID and borderline SID groups were pooled. In this total SID group slight infections prior to death was associated with deletion of either the C4A or the C4B gene (P = 0.033), and the SID victims with such infections had a higher deletion frequency than the controls (P = 0.039). There were no differences between the living infants with and without upper airway infections. Conclusion The present study confirms that partial deletions of the C4 gene in combination with slight upper airway infections may be a risk factor in sudden infant death. Received: 8 June 1998 / Accepted in revised form: 7 September 1998     

Precipitants in 42 cases of erythema multiforme

A total of 42 children with erythema multiforme (aged 0.1 to 15.8 years, median 6.1 years) were treated between 1978 and 1997 at the Department of Paediatrics, University of Bern, Switzerland. Antecedent infections were noted in 30 cases: Mycoplasma pneumoniae infection (n = 14), acute upper respiratory tract disease (n = 10) and herpes simplex infection (n = 6). Four cases were associated with antecedent medication (n = 3) or immunization (n = 1). In 12 of the 30 patients in whom erythema multiforme followed an infectious disease, drugs described in the literature as inducers of erythema multiforme had been given for symptoms not suggestive of the condition. In the remaining eight children no precipitating agent could be detected. Conclusion In this survey infections were found as a definite or at least presumptive trigger of erythema multiforme in 71% of cases. Drugs (including immunization) implicated as triggers of erythema multiforme played a definite causative role in 10% and a presumptive role in a further 29% of patients. In 19% of patients an associated condition was not diagnosed. Received: 1 September 1998 / Accepted in revised form: 16 April 1999     

Pseudomonas aeruginosa infections due to electronic faucets in a neonatal intensive care unit

Aim: To evaluate the role of electronic faucets in a newborn intensive care unit during a Pseudomonas aeruginosa outbreak. Methods: After three patients had P. aeruginosa bacteremia, environmental cultures including those from patient rooms, incubator, ventilators, total parenteral nutrition solutions, disinfection solutions, electronic and hand‐operated faucet filters/water samples after removing filters and staff hands were taken. Results: Only filters of electronic faucets and water samples after removing filters and one liquid hand soap showed P. aeruginosa (3–7 × 106 cfu/mL). We have removed the electronic faucets and new elbow‐operated faucets were installed. Pulsed‐field gel electrophoresis analysis of outbreak‐blood culture isolates from two patients and isolates from electronic water faucets/one liquid hand soap indicated the presence of 90.7% genetically related subtype, probably from the same clone. Water cultures from new faucets were all clean after installation and after 7 months. Conclusion: We suggest that electronic faucets may be considered a potential risk for P. aeruginosa in hospitals, especially in high‐risk units.