Skin Infections in Children

The treatment of skin and soft-tissue infections in pediatrics has been complicated by the constant increase of antibiotic resistance by Staphylococcus aureus. With a retrospective, case-control trial, the efficacy of a treatment, performed in Philadelphia through beta-lactamines, clindamycin or trimetoprim-sulphametoxazole (TMP-SMX) was evaluated in 2096 children (between 0 and 21) with skin infections diagnosed between 2004 and 2007. The use of clindamycin and of TMP-SMX increased from 16% in 2004 to 62% in 2007; there have been 104 cases of failure and 480 recoveries. The lack of recovery was defined by the need of implanting a drainage, of changing the antibiotic, of prescribing a second antibiotic or of hospitalizing the patient within 28 days from diagnosis. Compared to beta-lactamines, clindamycin presented a similar efficacy, while the TMP-SMX was independently associated with an increase in the risk of therapeutical failure (OR 2.35). Other factors independently associated with the lack of recovery were race (OR 2.43), fever (OR 1.94), the presence of an abscess (OR 1.88), antibiotic treatment in the 6 months preceding the infection (OR 1.76) and going to the Emergency Room at first instead of going to the GP (OR 2.77).

Given the fact that abscess diseases needing a drainage have been excluded from the trial, the result cannot be generalized to all skin and soft-tissue infections; in any case, if the infection is superficial and with no abscess (so, very probably caused by a Staphylococcus), the use of beta-lactamine or of clindamycin is the best choice, while TMP-SMX must not be advised, given the wide resistance that the bacterium presents towards this antibiotic association. If the culture shows the presence of a methicillin-resistant Staphylococcus, the use of TMP-SMX is indicated. In the presence of an abscess, it is necessary to lance and drain and, in this case, a recent trial has shown that the adding of TMP-SMX to the drainage doesn’t improve diagnosis.

Scarcely Controlled Asthma in Children

The traditional therapy for asthma in children implies the use of ion therapy based on inhaled cortisones, but when this therapy is insufficient, which is the next step? Three different therapies have been examined in 165 children (between 6 and 17 years of age) who had had no satisfying control after 2-8 weeks with inhaled fluticasone (100 μ twice a day). Subjects have been randomized in double blind and triple crossover to receive each of the following therapies for 16 weeks: inhaled fluticasone up to 250 μ twice a day; lower-dose fluticasone plus a long-acting beta-agonist at the dose of 50 μ a day; low-dose fluticasone plus an antagonist of leukotriene-receptors at the dose of 5-10 mg a day. The primary outcome was established in a composed result: FEV1 improvement, use of oral steroids, numbers of days when asthma symptoms have been under control. Almost all participants (about 98%) have shown an improvement. Among the three therapies, the best one was the association of fluticasone with a beta-agonist (52% of improvement vs. 34% for fluticasone and antileukotriene drugs; 54% vs. 32% for high-dose fluticasone). There has been no relation between therapeutical success and the subjects’ age, while the only relation was recorded with ethnic groups: black children have reacted in the same way both adding a beta-agonist and increasing fluticasone, while white children have shown the best results adding a beta-agonist.

The association of inhaled cortisones with beta-agonists represents, according to this trial, the best therapeutical option in children where the inhaled corticosteroid alone is not capable to keep asthma symptoms under control. But it is also necessary to remember that researchers have recently insisted on the harmfulness of these drugs, as they have found an association with an increased risk of asthma exacerbations and of sudden deaths, so the FDA recommends that they are used only for short periods of time and with high cortisone dosages. In spite of the results obtained in this trial, the increase in the corticosteroid or the association with antileukotriene agents is no doubt a safer choice as to severe side effects.

Screening for Neonatal Hyperbilirubinemia

In 2004, the American Academy of Pediatrics has given the recommendation to make newborns undergo the measurement of bilirubin levels, since kernicterus – even if extremely rare – implies dramatic and dreadful consequences. This recommendation, at least in the USA, has not been universally put into action and some trials have been recently performed in order to evaluate the spreading of this simple screening. In a retrospective trial performed in California, the incidence of neonatal hyperbilirubinemia before and after the screening was compared on at least 35-week-gestation newborns. Between 1995 and 2007, 319,904 children have been born and 38,182 have been born after the introduction of screening through blood sample or percutaneous evaluation. Screening was associated with a 62% reduction in bilirubin levels which, according to the recommendation of the American Academy of Pediatrics, require exchange transfusion. In the same time, there has been a more frequent use of phototherapy (9.1% vs. 4.2%). In a systematic review on 11 trials (involving about 125,000 children), the screening presented a good sensitiveness and specificity in discovering hyperbilirubinemia. In no trial the association between screening and hyperbilirubinemia-related encephalopathy has been evaluated. As to the U.S. Preventive Services Task Force (USPSTF), we can read that “the evidence is insufficient to recommend screening”. The discussion is still open.

kernicterus prevention is imperative, but this situation is very rare (1 case out of 100,000 newborns) and so the usefulness of screening is very difficult to establish, given the fact that parameters to be considered are many. An aspect not to be underestimated concerns the possible damages related to the screening (an increase in the use of phototherapy and an increase in hospitalizations). It would be opportune to perform a randomized trial to clear up the matter in a definitive way.

Antibiotic Prophylaxis for Pediatric Urinary Infections

According to recent trials, the use of antibiotics after a pediatric urinary infection doesn’t reduce relapses, but the matter is still under discussion. Some researchers in Australia have performed a multicentric trial randomizing 576 children (average age 14 months; 64 of them were females), with an anamnesis of urinary infection shown through uroculture, to receive a prophylaxis with a low-dose antibiotic (2 mg/kg of trimetoprim plus 10 mg/kg of sulfamethoxazole) or with placebo, for 12 months. During follow-up, children treated with antibiotic have presented less infectious recurrences with a statistically significant difference (13% vs. 19%; p=0.02). Most relapses have occurred in the 6 months following the beginning of the trial. The results of performed imaging tests presented no differences between the treated group and the control group. Prophylaxis seemed more effective in the prevention of urinary infections in children with III-IV-stage vesical-urethral reflux (difference in the absolute risk: 6.8%) than in children with I-II-stage reflux (5.4%) and in children with no reflux at all (1.8%).

The trial is well performed and the sample is sufficient; unfortunately, the primary outcome has been set as number of relapses rather than as the evaluation of long-term renal function, which, from a clinical point of view, has a far greater importance. In any case, it is fundamental to diagnose the presence and the severity of a possible vesical-urethral reflux, since the real modifiable risk factor is this condition. In children not presenting a reflux of great importance, antibiotic prophylaxis of relapses is not indicated; for the ones with III-stage or higher reflux, the matter is still debated.

Probiotics and Necrotizing Enterocolitis

A study published in 2008 has affirmed that in preterm newborns the use of probiotics is capable to prevent the development of a disease, which is unfortunately widespread and severe, necrotizing enterocolitis. With a meta-analysis of 11 randomized trials involving 2176 preterm newborns (birth weight lower than 1500 g), some researchers have now verified that the newborns treated with probiotics are significantly less affected by necrotizing enterocolitis (RR 0-35; NNT 25) and present an overall mortality lower than the non-treated ones (RR 0.42; NNT 20). The use of probiotics is not associated with an increase in other infections.

The meta-analysis confirms the usefulness of probiotics, even if it is not clear yet whether the use of these products is to enter the usual practice. Examining the meta-analysis with criticism, we neither know, for example, with which probiotic and at which dosage positive effects appear, nor whether its efficacy is conditioned, in some ways, by breastfeeding or by bottle feeding. No doubt, given their inexistent dangerousness, probiotics in these particular situations must be seriously taken into consideration.