There has been an increase in Mycoplasma pneumoniae (MP) respiratory infections over the past months, especially in children, per CDC.
MP infections are common, with an estimated 2 million infections occurring each year in the US. But the true number of people affected every year is unknown as there is no national reporting or dedicated surveillance system to track MP infections. School-age children and adolescents appear to be the most commonly affected age group.
“M. pneumoniae may be responsible for about 4 to 8% of community-acquired bacterial pneumonias (CABP) during periods of endemicity. However, this organism can cause up to 20 to 40% of CABP in the general population during epidemics, rising to as much as 70% in closed populations (see Jacobs et al 2015 and Loens et al 2010). An estimated 2 million cases occur annually, resulting in about 100,000 hospitalizations of adults in the United States (see Marston et al 1997 and Winchell 2013).”
-Waites et al, Clin Microbiol Rev. 2017
One of the challenges in diagnosing MP is that there are no clinical symptoms or signs in children and adolescents that reliably distinguish it from other lower respiratory tract illnesses. Its typical symptoms—slow progression of malaise, sore throat, low-grade fever, and cough—tend to mimic viral illnesses, noting that patients typically lack pharyngeal/tonsillar exudates or cervical lymphadenopathy. CXR findings are also non-specific, typically showing peribronchial and perivascular interstitial infiltrates and patchy airspace consolidations.
Diagnostic testing includes PCR (e.g., nasopharyngeal swab testing) and serology, noting that the latter lacks specificity and even has cross-reactivity with EBV; however, despite its excellent specificity, PCR testing may also be problematic. A Dutch study investigating the question of asymptomatic carriage of MP found +PCR testing in 21% of asymptomatic children (n = 405) and 16% of children with respiratory symptoms (n = 321) at a single site. The study also found that the MP organisms can persist for up to 4 months in the absence of clinical illness and that carriage rates were variable between seasons and sampling years. In contrast, US studies have found variable carriage rates, ranging from 0% (0 of 180 asymptomatic students aged 15-30yo at a student health clinic) to 56% (36 of 64 healthy controls aged 5-17yo).
“Testing for M. pneumoniae may be most useful when the pretest probability for M. pneumoniae infection is intermediate or high. The age at which one should begin to strongly consider M. pneumoniae as the cause of CAP is not well defined… Testing may not be necessary in children with a low likelihood of M. pneumoniae infection (eg, younger children with symptoms more compatible with a primary viral upper respiratory tract infection), in whom the positive predictive value of a positive test may only be modest (ie, false-positive results will occur). Testing may be most useful in guiding decisions regarding empiric antibiotic therapy in school-aged children and adolescents who have findings consistent with but not classic for M. pneumoniae infection. In these situations, a positive test result for M. pneumoniae may warrant treatment, whereas a negative result makes the diagnosis of M. pneumoniae pneumonia unlikely.”
-Bradley et al, Clin Infect Dis. 2011
Adding to the confusion is what to do about antibiotic therapy. Most MP infections are self-limiting and improve spontaneously within 7-10 days. Traditionally recommended antibiotics include either a macrolide, tetracycline, or fluoroquinolone, owing to MP’s lack of a cell wall (macrolides and tetracyclines, which are bacteriostatic, target the bacterial ribosome whereas fluoroquinolones, which are both bacteriostatic and bactericidal, inhibit DNA replication).
The 2011 IDSA guidelines on CAP management in kids offered the following recommendations relevant to MP:
- Children with signs and symptoms suspicious for MP should be tested to help guide antibiotic selection. (weak recommendation; moderate-quality evidence)
- Macrolide antibiotics should be prescribed for treatment of children (primarily school-aged children and adolescents) evaluated in an outpatient setting with findings compatible with CAP caused by atypical pathogens. Laboratory testing for MP should be performed if available in a clinically relevant time frame… (weak recommendation; moderate-quality evidence)
- Empiric combination therapy with a macrolide (oral or parenteral), in addition to a β-lactam antibiotic, should be prescribed for the hospitalized child for whom MP and C. pneumoniae are significant considerations; diagnostic testing should be performed if available in a clinically relevant time frame… (weak recommendation; moderate-quality evidence)
“It is likely that children with moderate to severe disease will benefit from treatment with macrolides or tetracyclines (for children >7 years). Therapy with the respiratory fluoroquinolones has demonstrated treatment outcomes for adults that are not inferior to macrolides and tetracyclines [see Mandell et al 2007 and Plouffe 2000]. Of note, for preschool children with Mycoplasma LRTI documented serologically, amoxicillin clavulanate demonstrated clinical outcomes equivalent to those for levofloxacin when evaluated for the primary end point of clinical cure at the test-of-cure visit, 10–17 days after the last dose of the study drug. These results suggest a high rate of spontaneous clinical resolution in Mycoplasma infection without need for antimicrobial therapy in this younger age group, although lack of benefit may have resulted from analysis at the test-of-cure visit, without an additional analysis for benefit at much earlier time points into therapy [see Bradley et al 2007].”
-Bradley et al, Clin Infect Dis. 2011
More recent data on first-line therapy with azithromycin shows questionable benefit in kids and that it may be no better than using beta-lactam monotherapy in treatment of CAP despite the fact that beta-lactams do not possess activity against MP.
Last, it’s important to note that antibiotics remain recommended for MP infections with extrapulmonary manifestations (in addition to pulmonary complications), which are uncommon overall but incredibly varied in scope:
- Cardiovascular: myocarditis, pericarditis, arrhythmia
- Derm: erythema nodosum, cutaneous leukocytoclastic vasculitis, erythema multiform, SJS, MP-associated mucositis
- GI: nausea, vomiting, abdominal pain, anorexia, diarrhea, elevated transaminases
- Heme: VTE, cytopenia, hemolytic anemia, ITP-like syndrome, DIC
- MSK: myopathy, arthritis, rhabdomyolysis, septic arthritis
- Neuro: encephalitis, aseptic meningitis, optic neuritis, GBS
- Ophtho: conjunctivitis, iritis, uveitis
- Pulm: pleural effusion, lung abscess/empyema, bronchiolitis obliterans, bronchiectasis, chronic interstitial fibrosis, ARDS
- Renal: ATN, glomerulonephritis, interstitial nephritis, nephrotic syndrome