Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau. Management for the children with otitis media with effusion in the tertiary hospital. Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial. Penicillin in acute otitis media: a double-blind placebo-controlled trial.
To investigate whether prophylactic antibiotics can prevent complications of measles.
                Community based, randomised, double blind, placebo controlled trial.
                Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa.
                84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war).
                Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days.
                Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media.
                The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups.
                The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries.
                Clinical trials NCT001168532. Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study.
                Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months.
                Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05).
                In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals. To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes.
                A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations <85% in air, shock requiring >20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age <6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be <38 degrees C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness.
                Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p<0.001 for equivalence). Three children in the oral group were changed to IV antibiotics and seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups.
                Oral amoxicillin is effective for most children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society guidelines on childhood pneumonia could not draw on evidence to address this issue. This will spare children and their families the trauma and pain of cannulation, and children will spend less time in hospital. The effect of peroral penicillin-V (55 mg/kg/day in 7 days) on acute otitis media was studied in 149 children between the ages of 1 and 10 years in a double-blind, placebo-controlled investigation. The parameters of the disease employed were symptom scores for earache, fever and common cold, the use of analgetics, otoscopy, as well as tympanometry. The children were followed-up for 3 months. Penicillin had no effect on fever and common cold, but earache was significantly reduced on the 2nd day of treatment. The acute course of the disease was satisfactory in 69% of the children in the placebo group and in 86% in the penicillin group. In patients with pneumococci or haemolytic streptococci in the nasopharynx, the pain disappeared after 1-2 doses of penicillin, whereas the treatment had no effect in children with Haemophilus influenzae. There was no difference between the penicillin and the placebo groups with regard to the results of otoscopy and tympanometry after 1 week, 1 month and 3 months. No serious complications were observed. It is concluded that an attitude of "masterly inactivity" with regard to the treatment of acute otitis media is justifiable, provided sufficient analgesic treatment is given and also that the patient can be closely followed. As there are still many unanswered questions more controlled investigations are warranted.
The studies reviewed were of poor quality and used older antibiotics. This review suggests a beneficial effect of antibiotics in preventing complications such as pneumonia, purulent otitis media and tonsillitis in children with measles. On the basis of this review, it is not possible to recommend definitive guidelines on the type of antibiotic, duration or the day of initiation. Use of penicillin or co-trimoxazole may be considered. There is a need for more evidence from high-quality RCTs to answer these questions.