ReviewEmerging resistance to antibiotics against respiratory bacteria: impact on therapy of community-acquired pneumonia in children
Introduction
Despite the availability of effective therapy, community-acquired pneumonia (CAP) in infants and children remains a significant problem worldwide (McIntosch, 2002, Selwyn, 1990, Baqui et al., 1998, Brown and Lerner, 1998, Marrie, 1994, Mulholland, 1999). In developing countries, it is very common and severe and the largest killer of children (McIntosch, 2002, Selwyn, 1990, Baqui et al., 1998); in the industrialized world, it involves substantial morbidity-related costs to society and the health care system (Brown and Lerner, 1998, Marrie, 1994, Mulholland, 1999).
Over the last few years, difficulties related to CAP in children have greatly increased because of the emergence of resistance to the most widely used antibiotics against some of the bacterial pathogens involved in the development of the disease (Heffelfinger et al., 2000, Heffelfinger et al., 2000, Finch, 2001, McCracken, 2000a, Musher et al., 2002). This paper describes the impact of such resistances on the outcome of CAP in pediatrics and possible changes in antibiotic therapy regimes to overcome them.
Section snippets
Etiology of CAP in children
The etiology of CAP is much more difficult to identify in children than in adults because lower-airway secretions can rarely be obtained and invasive methods of diagnosis cannot be routinely applied (Thomson, 1999, Menendez et al., 1999, Jadavji et al., 1997). In addition, as in the case in adults, cultures of the upper respiratory tract secretions are not useful as the normal flora include the bacteria commonly responsible for pneumonia (McIntosch, 2002). This may explain why most of the
Diagnosis
The definitions of pneumonia vary widely. Some require only the presence of infiltrates or consolidations on a chest radiograph, and others only certain respiratory symptoms or signs (Murphy et al., 1981, World Health Organization, 1981). The World Health Organization has defined pneumonia solely on the basis of clinical findings obtained by visual inspection and by timing the respiratory rate (Bachur et al., 1999). However, there is ample evidence that a chest radiograph is useful to confirm
Emerging resistance of bacterial pathogens of pediatric CAP
Several reports of bacteria with a reduced susceptibility to antibiotics had been published by the end of the 1960s, and this problem has grown in recent years. The development of resistance is of particular concern when treating respiratory tract infections, for which antibiotics are most frequently used.
Among the bacterial pathogens that play the greatest role in causing pediatric CAP, the most significant changes in sensitivity to antibiotics have been observed in the case of S. pneumoniae
Penicillin resistance
The resistance of S. pneumoniae to penicillin and other beta-lactams is related to target-mediated changes in the size and configuration of the PBPs that enable the cross-linking of bacterial cell wall precursors (Kellner, 2001, Bauer et al., 2001, Klugman, 1996, Mlynarczyk et al., 2001). These changes lead to a decrease in PBP affinity for penicillin and thus increase penicillin resistance. Resistance develops in a stepwise and apparently irreversible manner because of mutations in one or more
Suggested therapeutic regimens in children with CAP
Because definite information about the causative pathogens is seldom available, the treatment of CAP is usually empiric.
It is first necessary to decide whether or not to withhold antibiotic treatment. Some clinicians suggest that antibiotic therapy is always indicated in CAP because of the difficulty of excluding the possibility of bacterial infection (Ruuskanen and Mertsola, 1999). Others—including ourselves—believe that antibiotic therapy can be withheld in mildly ill patients with probable
New antibiotics for the therapy of CAP in children
Several new drugs have been developed to overcome the resistance of respiratory pathogens to the antibiotics usually used to treat CAP (McIntosch, 2002, Cazzola et al., 2001, Lee et al., 1999, Moellering, 1998). However, few pediatric clinical trials have yet been performed, and we do not know the real safety and tolerability of these compounds in children. Only their clinical use will establish whether they will play an innovative role in the treatment of childhood CAP.
Screening for isolated
Conclusions and future directions
Possibly because of its etiologic complexity, CAP remains a common illness and a major cause of childhood morbidity worldwide. The use of treatment algorithms in industrialized countries has led to lower mortality rates but, given the rate of development of antimicrobial resistance, the future of this approach is uncertain. The past decade has witnessed a dramatic increase in the prevalence of antimicrobial resistance in respiratory pathogens, such as S. pneumoniae and H. influenzae, much of
References (99)
- et al.
High serum procalcitonin concentrations in patients with sepsis and infection
Lancet
(1993) - et al.
Occult pneumonias: empiric chest radiographs in febrile children with leukocytosis
Ann. Emerg. Med.
(1999) - et al.
Streptococcus pneumoniae in community-acquired pneumonia? How important is drug resistance?
Med. Clin. North Am.
(2001) - et al.
Community-acquired pneumonia
Lancet
(1998) - et al.
Break-through bacteremia and meningitis during treatment parenterally with cephalosporins for pneumococcal pneumonia
J. Pediatr.
(1998) - et al.
Advances in the research and development of chemotherapeutic agents for respiratory tract bacterial infections
Pulm. Pharmacol. Ther.
(2001) - et al.
Oxazolidinone antibiotics
Lancet
(2001) Pneumococcus resistant to eryhthromycin and lincomycin
Lancet
(1967)- et al.
The role of atypical pathogens: Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila in respiratory infection
Infect. Dis. Clin. North Am.
(1998) Community-acquired pneumonia: the evolving challenge
Clin. Microbiol. Infect.
(2001)
What’s new in the antibiotic pipeline
Curr. Opin. Microbiol.
Epidemiological aspects of antibiotic resistance in respiratory pathogens
Intern. J. Antimicrob. Agents
Magnitude of the problem of childhood pneumonia
Lancet
Emerging role of Mycoplasma pneumoniae and Chlamydia pneumoniae in paediatric respiratory tract infections
Lancet Infect. Dis.
Pneumococcal macrolide resistance: myth or reality?
J. Antimicrob. Chemother.
Overview of recent developments in carbapenem and trinem antibiotics
Curr. Opin. Anti-infect. Invest. Drugs
Causes of childhood deaths in Bangladesh: results of a nationwide verbal autopsy study
Bull. World Health Organ.
Telithromycin
Drugs
Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children
Pediatr. Infect. Dis. J.
Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric communityacquired pneumonia: comparative efficacy and safety of clarithromycin versus erythromycin ethylsuccinate
Pediatr. Infect. Dis. J.
Expanded activity and utility of the new fluoroquinolones: a review
Clin. Ther.
Novel oral cephalosporins
Exp. Opin. Invest. Drugs
Clinical outcome of invasive infections by penicillin-resistant Streptococcus pneumoniae in Korean children
Clin. Infect. Dis.
Accuracy of radiographic differentiation of bacterial from non-bacterial pneumonia
Clin. Pediatr.
Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men
Clin. Infect. Dis.
Reliability of the chest radiograph in the diagnosis of lower respiratory infections in young children
Pediatr. Infect. Dis. J.
Risk factors and course of illness among children with invasive penicillin-resistant Streptococcus pneumoniae
Pediatrics
Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of β-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study
Antimicrob. Agents Chemother.
Prevalence of antimicrobial resistance among respiratory tract isolates of Streptococcus pneumoniae in North America: 1997 results from the SENTRY Antimicrobial Surveillance Program
Clin. Infect. Dis.
Antimicrobial resistance with Streptococcus pneumoniae in the United States 1997–1998
Emerg. Infect. Dis.
Characteristics of Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with pneumonia
Eur. Resp. J.
Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance 1995–1997
Am. J. Public Health
The Alexander Project 1996–1997: latest susceptibility data from this international study of bacterial pathogens from community-acquired lower respiratory tract infections
J. Antimicrob. Chemother.
Community-acquired pneumonia: new guidelines for management
Curr. Opin. Infect. Dis.
Etiology of acute lower respiratory tract infections in Gambian children. I. Acute lower respiratory tract infections in infants presenting at the hospital
Pediatr. Infect. Dis. J.
Increase in community-acquired methicillin-resistant Staphylococcus aureus in children
Clin. Infect. Dis.
Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease
Pediatr. Infect. Dis. J.
The clinical impact of macrolide resistance in pneumococcal respiratory infections
Intern. J. Antimicrob. Agents
Resistance of bacteria to erythromycin
Proc. Soc. Exp. Biol. Med.
Peptide antibiotics
Antimicrob. Agents Chemother.
Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children
Pediatr. Infect. Dis. J.
The contribution of specific pneumococcal serogroups to different disease manifestations: implications for conjugate vaccine formulation and use. Part II
Clin. Infect. Dis.
Management of community-acquired pneumonia in the era of pneumococcal resistance
Arch. Intern. Med.
Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group
Arch. Intern. Med.
Etiology of childhood pneumonia: serologic results of a prospective, population-based study
Pediatr. Infect. Dis. J.
Extremely high incidence of macrolide and trimethoprim-sulfamethoxazole resistance among clinical isolates of Streptococcus pneumoniae in Taiwan
J. Clin. Microbiol.
Macrolide resistance among invasive Streptococcus pneumoniae isolates
JAMA
Cited by (23)
Antibiotic administration and the development of obesity in children
2016, International Journal of Antimicrobial AgentsAppropriate use of fluoroquinolones in children
2015, International Journal of Antimicrobial AgentsCitation Excerpt :With the increasing resistance to antibiotics among common bacterial pathogens [1,2], challenges regarding the potential use of fluoroquinolones (FQs) in paediatrics have emerged.
Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia
2011, Respiratory MedicineManagement of severe community-acquired pneumonia of children in developing and developed countries
2011, ThoraxCitation Excerpt :These data confirm the previous findings of Tan et al19 and Michelow et al.20 Some authors have tried to use chest radiography to improve the definition of severe CAP but, although some studies indicate that lung consolidation is associated with greater clinical involvement, this is not confirmed by a global evaluation of all of the available data.21–24 It has long been known (mainly on the basis of lung puncture studies carried out in developing countries) that mild and moderate CAP is mainly caused by viruses, particularly in the first years of life, whereas most cases of severe CAP are caused by bacteria.1–4
Community-Acquired Pneumonia Due to Virus and Mycoplasma pneumoniae Infection in Children Younger than 5 Years
2019, Journal of Pediatric Infectious Diseases