Source: Anti-Cancer Drugs  |  Posted 4 years ago

By Chris Berrie

MUNICH, GERMANY -- April 9, 2007 -- Combinations of a beta-lactamase inhibitor with a penicillin produce a satisfactory therapeutic outcome in paediatric patients with lower respiratory tract infections (LRTIs), according to a retrospective study.

Principal investigator Naruhiko Ishiwada, MD, PhD, lecturer, department of paediatrics, Chiba University Graduate School of Medicine, Chiba, Japan, presented the study results here at the joint 17[^]th[] European Congress of Clinical Microbiology and Infectious Diseases and 25[^]th[] International Congress on Chemotherapy (ECCMID-ICC).

Paediatric LRTIs are a common cause of morbidity and mortality worldwide, with Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis as the main causative bacterial agents, Dr. Ishiwada said in a presentation on April 2[^]nd[].

The prevalence of penicillin-resistant S. pneumoniae and ampicillin-resistant H. influenzae, and particularly beta-lactamase non-producing ampicillin-resistant (BLNAR) H. influenzae, has seen a remarkable increase in Japan in recent years. Similarly, almost all of the M. catarrhalis isolated from patients with LRTIs are beta-lactamase-producing strains. It is therefore becoming increasingly difficult to treat children with LRTIs with antibiotics.

Dr. Ishiwada and colleagues therefore designed their study to assess the efficacy and safety of 2 specific combinations of a beta-lactamase inhibitor with a penicillin: tazobactam plus piperacillin (TAZ/PIPC) and sulbactam plus ampicillin (SBT/ABPC), as initial treatments of hospitalised paediatric patients with LRTIs.

Of 108 paediatric inpatients enrolled, 64 were treated with TAZ/PIPC at 125 mg/kg/day, and 44 with SBT/ABPC at 150 mg/kg/day. Of these patients, 85% to 90% were 5 years or younger; the mean treatment group ages were 37.8 months and 32.0 months, respectively.

Clinical diagnoses were bronchitis (18.8% vs 15.9%, respectively), bronchiolitis (12.5% vs 9.1%) and pneumonia (68.7% vs 75.0%). The underlying diseases were: bronchial asthma (18.8% vs 18.2%), immunodeficiency (7.8% vs 0.0%) and other causes (14.0% vs 34.1%). No underlying disease were seen in 59.4% and 47.7% of patients, respectively.

Clinical assessment of these patients was based on a defined 5-level score: excellent, good, fair, poor, unable to evaluate. The antibiotic susceptibilities of the causative bacteria were investigated through sputum samples obtained with a tongue depressor with a light that was used to depress the tongue and induce a cough reflex. The sputum was then picked out using a swab of a 1-mL disposable syringe.

Mean duration of treatment was 6.0 days for TAZ/PIPC treatment (range, 3-21 days) and 5.1 days for SBT/ABPC(range, 3-9 days). Excellent/good clinical responses were obtained for 89.1% and 86.4%, respectively. The only adverse event noted was diarrhoea, with 2 and 1 patient, respectively.

A range of causative bacteria were isolated. These fell into the main species groupings of H. influenzae (39.0% vs 20.5%), S. pneumoniae (12.5% vs 11.4%) and M. catarrhalis (3.1% vs 18.2%). Combinations of these species were also seen, and Staphylococcus pyogenes was found in 1 patient in the TAZ/PIPC group, with 1 methicillin-susceptible S. aureus (MRSA) strain in a patient in the SBT/ABPC group.

Of note, 28.1% and 29.5% of patients had no pathogenic bacteria found in sputum samples, respectively.

The researchers also analysed the clinical response according to bacterial isolates, although with relatively small patient numbers across the full range of treatments and isolates.

The combination of TAZ/PIPC was effective for treatment of LRTIs due to beta-lactamase-non-producing ampicillin-resistant H. influenzae, the researchers concluded.

While both combinations produced good clinical responses and are good candidates for the treatment of children with LRTIs, TAZ/PIPC could be a useful combination for LRTIs due to antimicrobial resistant H. influenzae.

[Presentation title: Comparison of Sulbactam/Ampicillin and Tazobactam/Piperacillin for the Treatment of Lower Respiratory Tract Infection in Paediatric Patients. Abstract P1534]