15.5 Ureaplasmas, Mycoplasmas and neonatal pneumonia

There have been reports of congenital and neonatal pneumonia, including fatal cases, in which either U. urealyticum or M. hominis was the only pathogen isolated from the respiratory tract.1 Neonates with Ureaplasma pneumonia have had concurrent bloodstream isolation of Ureaplasmas occasionally.1 While most infants were pre-term, a case report describes a term infant with fatal congenital pneumonia, presumably acquired intrauterine, from which U. parvum was the sole organism cultured.15 While it has been argued that “the ability of Ureaplasma species and M. hominis to cause pneumonia, bacteraemia and meningitis in newborns can no longer be questioned,”1 Mycoplasmas and Ureaplasmas may be cleared spontaneously without specific antibiotic treatment from the respiratory tract, bloodstream or CSF and it has been problematic to demonstrate that antibiotics make any difference to the clinical course of neonatal Ureaplasma or Mycoplasma infection.

15.6 Ureaplasmas and chronic lung disease of prematurity

The association between neonatal U. urealyticum respiratory tract colonization and chronic lung disease of prematurity or BPD has been described in a number of case-control studies.6,12,16–26 There are some reservations, however, regarding the strength of the association and causality. A 1993 critical appraisal of four studies found that the association between U. urealyticum colonization and chronic lung disease was not observed in infants <;1250 g, while uncolonized infants <;750 g had such a high risk (82%) of chronic lung disease that no association with colonization could be demonstrated.27 A more recent critical appraisal of 23 studies (2216 infants) found a significant association between U. urealyticum colonization and BPD at age 28 days or at 36 weeks post-menstrual age, but found substantial heterogeneity with the greatest contribution to the effect from small studies enrolling fewer than 100 infants each, suggesting possible publication bias.28

A Cochrane systematic review 29 found only two RCTs of macrolides and BPD in patients colonized with U. urealyticum.30,31 In one study colonized neonates <;30 weeks of gestation who were intubated received erythromycin (40 mg/kg/day) or placebo for 10 days, started at a mean age of 7 days: erythromycin did not reduce rates of BPD.30 Only 28 patients in this study had U. urealyticum colonization, of whom 5 had positive nasopharyngeal but negative endotracheal cultures; 14 of the 28 were treated with erythromycin; repeat cultures were negative in 12 of these 14 whereas untreated patients remained culture positive.30 However, there was no clinical improvement. In the other study, infants <;30 weeks of gestation (irrespective of Ureaplasma status) were randomized to prophylactic erythromycin or placebo. There was no reduction in the rate of BPD, but the study was seriously underpowered.31

A subsequent study found that neither 5 nor 10 days of intravenous erythromycin eradicated U. urealyticum colonization in infants <;1500 g,32 a result discordant with the previously described study,30 despite using similar doses and duration of erythromycin.

Two more recent RCTs of macrolides reported slightly more promising results. A trial of 6 weeks of azithromycin prophylaxis of infants <;1250 g demonstrated no significant reduction in death or BPD.33 However, the incidence of BPD in infants colonized with Ureaplasma was 73% with azithromycin versus 94% with placebo (p = 0.03). Sub-analysis demonstrated a decrease in BPD or death in the azithromycin group (estimated OR 0.026, 95% CI 0.001–0.618).33 As the benefit of azithromycin was confined to infants colonized with Ureaplasma, azithromycin was presumably acting through an antimicrobial rather than an anti-inflammatory mechanism.

In a single centre, unblinded study from Turkey, infants 750–1250 g colonized with U. urealyticum received 10 days of intravenous clarithromycin or placebo.34 One of 35 (2.9%) treated with clarithromycin developed BPD compared with 12 of 33 (36.4%) placebo recipients (p <; 0.001), although U. urealyticum was eradicated in only 68.5% of patients treated with clarithromycin.34 The results are surprisingly different from other macrolide studies. The authors suggest clarithromycin may have better in vitro activity than erythromycin against U. urealyticum and better penetration into bronchial mucosa and secretions. There was no difference in duration of mechanical ventilation or in mortality, so the clinical significance is uncertain.34

Safety may be a concern. There is an association between erythromycin and pyloric stenosis,35,36 and pyloric stenosis was also described in two of three triplets given azithromycin,37 which suggests a possible class effect of macrolides.

15.7 Mycoplasma hominis, Ureaplasma and central nervous system infection

There are around 30 reports of M. hominis meningitis and/or brain abscess in neonates.1,35,36,38 Meningitis may be associated with intraventricular haemorrhage and hydrocephalus, is often diagnosed late and the outcome is usually poor. Most infants are pre-term although cases occur in full-term infants.1 U. urealyticum and U. parvum have also been isolated as the sole organism from the CSF of pre-term and full-term infants with proven or suspected meningitis.1,39,40 Both M. hominis and a Ureaplasma species were isolated from one infant with a brain abscess.41 The organism may also be isolated from the bloodstream.1 These cases are clinically convincing, but the response to antibiotics is often poor.

However, the interpretation of finding M. hominis or Ureaplasma in CSF is complicated. Symptoms can vary from none (asymptomatic) to severe neurologic impairment, sometimes fatal. The CSF cell count and chemistry is often normal and the organisms may persist with or without treatment.1,42,43 U. urealyticum infection and CSF pleocytosis sometimes resolve spontaneously without antibiotics.44

For these reasons the decision to treat an infant for M. hominis or Ureaplasma CNS infection needs to be made on an individual basis.

15.8 Treatment of Mycoplasma or Ureaplasma

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