Mechanism of resistance acquisition and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children

Abstract

Mycoplasma pneumoniae pneumonia (MPP) is one of the most common forms of community-acquired pneumonia in children and adolescents. Outbreaks of MPP occur in 3- to 7-year cycles worldwide; recent epidemics in Korea occurred in 2006–2007, 2011, and 2015–2016. Although MPP is known to be a mild, self-limiting disease with a good response to macrolides, it can also progress into a severe and fulminant disease. Notably, since 2000, the prevalence of macrolide-resistant MPP has rapidly increased, especially in Asian countries, recently reaching up to 80%–90%. Macrolide-resistant Mycoplasma pneumoniae (MRMP) harbors a point mutation in domain V of 23S rRNA with substitutions mainly detected at positions 2063 and 2064 of the sequence. The excessive use of macrolides may contribute to these mutations. MRMP can lead to clinically refractory pneumonia, showing no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. Refractory MPP is characterized by an excessive immune response against the pathogen as well as direct injury caused by an increasing bacterial load. A change of antibiotics is recommended to reduce the bacterial load. Tetracyclines or quinolones can be alternatives for treating MRMP. Otherwise, corticosteroid or intravenous immunoglobulin can be added to the treatment regimen as immunomodulators to down-regulate an excessive host immune reaction and alleviate immune-mediated pulmonary injury. However, the exact starting time point, dose, or duration of immunomodulators has not been established. This review focuses on the mechanism of resistance acquisition and treatment options for MRMP pneumonia.

Challenges in Identifying Antibiotic Resistance Targets for Point-of-Care Diagnostics in General Practice

“…Just some of the antibiotic resistances associated with these combinations of antibiotics include hyper production of penicillinases, plasmidal resistances, point mutations, efflux pumps, etc. [15][16][17]. Such a diversity of antimicrobial resistance mechanisms means that it is unlikely (or feasible) to develop a POC diagnostic that can detect all of the different antibiotic resistances described in the scientific literature.…”

Additional corticosteroids or alternative antibiotics for the treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia

“…Yang et al10) reviewed the mechanism of resistance acquisition by MP, and discussed the issue of alternative antibiotics or additional immune-modulators for treating MRMP pneumonia. For patients with severe progressive MRMP pneumonia, Yang et al10) recommend the use of alternative antibiotics, and/or the addition of systemic immune-modulators (corticosteroids and/or intravenous immunoglobulin).…”

“…Yang et al10) reviewed the mechanism of resistance acquisition by MP, and discussed the issue of alternative antibiotics or additional immune-modulators for treating MRMP pneumonia. For patients with severe progressive MRMP pneumonia, Yang et al10) recommend the use of alternative antibiotics, and/or the addition of systemic immune-modulators (corticosteroids and/or intravenous immunoglobulin). We suspect that many pediatricians treating protracted MRMP pneumonia in Korea, and possibly in other MRMP endemic countries, would choose the latter method, based on experience with immune-modulators during previous MP pneumonia epidemics, as cited by Yang et al10).…”

“…For patients with severe progressive MRMP pneumonia, Yang et al10) recommend the use of alternative antibiotics, and/or the addition of systemic immune-modulators (corticosteroids and/or intravenous immunoglobulin). We suspect that many pediatricians treating protracted MRMP pneumonia in Korea, and possibly in other MRMP endemic countries, would choose the latter method, based on experience with immune-modulators during previous MP pneumonia epidemics, as cited by Yang et al10). Quinolones and tetracycline are not recommended in pediatric patients because of potential side effects such as arthropathy or tooth discoloration, and the use of these alternative antibiotics is not approved by the Korean Food and Drug Administration at present time10).…”

“…We suspect that many pediatricians treating protracted MRMP pneumonia in Korea, and possibly in other MRMP endemic countries, would choose the latter method, based on experience with immune-modulators during previous MP pneumonia epidemics, as cited by Yang et al10). Quinolones and tetracycline are not recommended in pediatric patients because of potential side effects such as arthropathy or tooth discoloration, and the use of these alternative antibiotics is not approved by the Korean Food and Drug Administration at present time10). During advanced MP pneumonia, host cell-derived substances from injured lung tissue may induce more inflammation, affecting the corresponding immune cells and prolonging morbidity; thus, early control of disease progression is important11).…”