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Increasing resistance to first line antibiotics means recommendations need changing
Despite advances in our understanding of the epidemiology and distribution of deaths from pneumonia,1 more than 150 million cases of pneumonia still occur annually, with almost 2.4 million deaths worldwide. Pneumonia is perhaps the most frequent cause of death in children under 5, including during the newborn period.2 Deaths from pneumonia in children have increased in the wake of the HIV epidemic in Africa. Most deaths occur early in the course of illness. Because severe pneumonia is usually related to bacterial infection, treatment has largely focused on various antibiotic strategies.
In the accompanying randomised controlled trial, Asghar and colleagues compare the effectiveness of injectable ampicillin plus gentamicin or chloramphenicol in children aged 2-59 months with severe pneumonia (defined by World Health Organization criteria).3 The trial took place in inpatient wards in tertiary care hospitals in Bangladesh, Ecuador, India, Mexico, Pakistan, Yemen, and Zambia. Significantly more children failed treatment with chloramphenicol at five days (16% v 11%, relative risk 1.43, 95% confidence interval 1.03 to 1.97).
The study is one of a series of recent studies aiming to improve the treatment of childhood pneumonia in various settings.4 5 These findings confirm that the increasing resistance of common respiratory bacterial pathogens like Streptoccoccus pneumoniae and Haemophilus influenzae to first line antibiotics, such as co-trimoxazole and chloramphenicol, means that recommendations for treating suspected and confirmed pneumonia need to be changed.
Several limitations must be kept in mind before generalising these findings to the treatment of all children with very severe pneumonia. The study was restricted to children older than 2 months and might not apply to a large proportion of newborns and young infants who may have a different cause of pneumonia. Children with empyema or overt pneumatoceles (suggestive of possible Staphylococcus aureus infection) were excluded. Similarly, children with wheezing were not included, which potentially limits the applicability of these findings to children with secondary infections related to infection with respiratory syncytial virus or other viruses.6
Given that most deaths from pneumonia occur early in the course of the illness, health workers using the integrated management for childhood illness guidelines need to have clear algorithms for triage, stabilisation of children, and initiation of antibiotics. The antibiotic regimens for treating non-severe, severe, and very severe pneumonia should therefore form a continuum that is easy for health systems to implement and monitor on a large scale.
Despite the above limitations, given the increasing rates of drug resistance in common bacteria that cause pneumonia—such as Streptococcus pneumoniae and Haemophilus influenzae7—the current study supports the switch to more effective antibiotics. However, the combination of ampicillin and gentamicin may not be the best choice for developing countries. The need for multiple doses when using this combination may cause problems and lead to reduced adherence. The combination has limited coverage against Staphylococcus aureus, and there are legitimate concerns about the spectrum of pathogens that it covers. The spectrum of respiratory infections may have changed in regions where Haemophilus influenzae type B vaccine or the new pneumococcal conjugate vaccines have been introduced to include infections with non-vaccine strains as well as Gram negative pathogens.
The growing HIV epidemic in Africa has also altered the epidemiology and spectrum of lower respiratory tract infections in infected children. Cytomegalovirus, Pneumocystis jiroveci, and multi-drug resistant non-typhoidal Salmonella are now well known to cause pneumonia in children in Africa.8 Acute pulmonary tuberculosis may also present with features suggestive of severe pneumonia and must be kept in mind in susceptible populations.
It may be better to use once daily injectable cephalosporins such as ceftriaxone or fluoroquinolones for treating children with very severe pneumonia who require hospital admission or observed ambulatory therapy.9 However, the blanket use of second line antimicrobial agents in pneumonia makes the emergence of future resistance more likely, so tighter objective criteria are needed for diagnosing severe or very severe pneumonia. Many viral lower respiratory tract infections present with tachypnoea and chest recessions, and it may be difficult to distinguish them from bacterial infections on clinical criteria alone.10 Although recent studies do not indicate a good correlation between radiological results and clinically defined pneumonia,11 the use of portable pulse oximetry may help triage children for hospital admission and additional treatment, such as oxygen and injectable antibiotics.12 This approach needs to be validated in studies of appropriate diagnostic tools, including newer molecular methods that enable viral and bacterial infections (or combinations of the two) to be identified.
In the long term, the most cost effective way to reduce childhood mortality from pneumonia is to scale up effective evidence based preventive strategies. These strategies include promoting effective childhood immunisations (especially against measles, invasive Haemophilus influenzae type B, pneumococcal infections, and possibly influenza), improving environmental conditions through clean water and sanitation, and reducing indoor air pollution. In addition, improving nutrition at a population level may reduce intrauterine growth retardation and deficiencies in micronutrients, such as zinc and vitamin A. The challenge is to make this happen on a large scale.
Competing interests: None declared.
Provenance and peer review: Commissioned; not externally peer reviewed.