Oral antibiotics showed similar efficacy, safety to injectable antibiotics for bacterial infections

Issue: May 2015

Simplified outpatient antibiotic regimens safely and effectively treated possible severe bacterial infections among infants whose families do not accept or cannot access hospital care, according to results from three large trials conducted in Africa and Bangladesh published in The Lancet and The Lancet Global Health.

“Together, pneumonia, sepsis and meningitis cause about 700,000 deaths in neonates every year,” researchers from the African Neonatal Sepsis Trial (AFRINEST) group wrote in The Lancet. “Differentiation of these conditions on the basis of clinical presentation is difficult, so WHO recommends referral to hospital for neonates and young infants aged 1 month or older with clinical signs of possible serious bacterial infection, including fever, low body temperature, fast breathing (≥ 60 breaths per minute), severe chest indrawing, inability to feed well, convulsions, and movement only when stimulated or no movement at all.”

To compare efficacy of oral amoxicillin vs. injectable procaine benzylpenicillin-gentamicin for treatment of fast breathing, researchers randomized 2,333 infants with fast breathing as the only sign of possible serious bacterial infection to receive either treatment for 7 days. Parents of study participants (aged 0 to 59 days) did not accept referral to the hospital. The study was conducted across 5 study sites in the Democratic Republic of Congo, Kenya and Nigeria.

Nineteen percent of infants who received oral amoxicillin experienced treatment failure, compared with 22% among those who received injectable procaine benzylpenicillin-gentamicin (risk difference = –2.6%; 95% CI, –6 to 0.8).

Four infants in each treatment group died within 15 days of follow-up. There were no treatment-related adverse events.

Results from a second multisite, open label equivalence trial conducted by the AFRINEST group indicated comparable efficacy and safety of inpatient and outpatient treatment for possible serious bacterial infection.

Researchers randomized 3,564 infants with clinical signs of severe infection whose parents refused hospital referral to injectable procaine benzylpenicillin-gentamicin for 7 days (group A), injectable gentamicin and oral amoxicillin for 7 days (group B), injectable procaine benzylpenicillin-gentamicin for two days followed by oral amoxicillin for 5 days (group C) or injectable gentamicin for two days followed by oral amoxicillin for 7 days (group D).

By day 8, all four treatment groups had similar treatment failure rates, ranging from 5% in group D to 8% in group A.

“For the first time we show that young infants with signs of suspected severe infection whose parents do not accept referral or cannot access a hospital can be managed with simplified antibiotic treatment in clinics under the supervision of a skilled health worker,” study researcher Fabian Esamai, PhD, of the University of Kenya, said in a press release.

A third study, conducted by Abdullah H. Baqui, DrPH, of Johns Hopkins Bloomberg School of Public Health, and colleagues across urban and rural sites in Bangladesh, provided further evidence that two alternative antibiotic regimens for outpatient treatment of clinical signs of severe infection had comparable efficacy with the standard regimen.

Study participants (aged 0 to 59 days) who presented with at least one clinical symptom of severe infection were randomized to intramuscular procaine benzylpenicillin and gentamicin for 7 days (n = 830), intramuscular gentamicin once a day plus oral amoxicillin twice a day for 7 days (n = 831) or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice a day for 5 days (n = 829).

Treatment failure rates were low and similar (ranging from 8% to 10%) across the three treatment groups, as were non-fatal relapse rates.

“These alternative treatment regimens could be easier to deliver and would provide treatment options for many more infants with suspected severe bacterial infections,” Baqui said in a press release. “However, safe delivery of these new treatment options will need substantial input into training and strengthening of primary health care systems.” – by Amanda Oldt

References:

Baqui AH, et al. Lancet Glob Health. 2015; doi:10.1016/S2214-109X(14)70347-X.

African Neonatal Sepsis Trial group. Lancet. 2015; doi:10.1016/S0140-6736(14)62284-4.

African Neonatal Sepsis Trial group. Lancet. 2015; doi:10.1016/S1040-6736(14)62285-6.

Disclosure: The AFRINEST studies were funded by the Bill and Melinda Gates Foundation. The study by Baqui and colleagues received funding from the Bill and Melinda Gates Foundation, Johns Hopkins School of Public Health, Save the Children U.S., USAID and WHO. Please see the full study for a list of all other authors’ relevant financial disclosures.