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Ureaplasma species are increasingly recognized as relevant pathogens in prenatal, perinatal and postnatal morbidity. They are commonly found as commensals on the mucous membranes of the lower urogenital tract of pregnant women, but when ascending, they can cause bacterial vaginosis, chorioamnionitis, premature birth and postnatal morbidities such as bronchopulmonary dysplasia, and early-onset neonatal sepsis and meningitis. The detection of Ureaplasma species is challenging and is not covered by routine diagnostics, and current empiric antibiotic treatment in neonates suspected of infection is not directed against Ureaplasma species. The aim of this review is to discuss the pathophysiology of Ureaplasma infections, the clinical consequences and the current difficulties in diagnosis and treatment by providing an overview of the current literature., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ureaplasma spp. respiratory tract colonization is a risk factor for bronchopulmonary dysplasia (BPD) in preterm infants, but differences in host susceptibility have not been elucidated. We hypothesized that variants in genes regulating the innate immune response are associated with altered risk for Ureaplasma spp. respiratory colonization and BPD in preterm infants., Methods: Twenty-four tag single nucleotide polymorphisms (SNPs) from Toll-like receptor (TLR)1, TLR2, TLR4 and TLR6 were assayed in 298 infants <33 weeks gestation who had serial respiratory cultures for Ureaplasma spp. and were evaluated for BPD., Results: The majority of subjects (N = 205 [70%]) were African-American. One hundred ten (37%) were Ureaplasma positive. Four SNPs in TLR2 and TLR6 were significantly associated with Ureaplasma respiratory tract colonization. Single SNPs in TLR2, TLR4 and TLR6 were associated with BPD. TLR6 SNP rs5743827 was associated with both a decreased risk for Ureaplasma respiratory tract colonization and decreased risk for BPD (odds ratio: 0.54 [0.34-0.86] and odds ratio: 0.54 [0.31-0.95], respectively). There was a significant additive interaction between Ureaplasma colonization and genotype at TLR6 SNP rs5743827 (Padditive = 0.023), with an attributable proportion due to interaction of 0.542., Conclusions: Polymorphisms in host defense genes may alter susceptibility to Ureaplasma infection and severity of the inflammatory response contributing to BPD. These observations implicate host genetic susceptibility as a major factor in BPD pathogenesis in Ureaplasma-infected preterms.

Background: Ureaplasma respiratory tract colonization is a risk factor for bronchopulmonary dysplasia (BPD) in preterm infants, but whether Ureaplasma isolates from colonized infants can form biofilms is unknown. We hypothesized that Ureaplasma isolates vary in capacity to form biofilms that contribute to their antibiotic resistance and ability to evade host immune responses. Study objectives were to (1) determine the ability of Ureaplasma isolates from preterm neonates to form biofilms in vitro; (2) compare the susceptibility of the sessile and planktonic organisms to azithromycin (AZI) and erythromycin; and (3) determine the relationship of biofilm-forming capacity in Ureaplasma isolates and the risk for BPD., Methods: Forty-three clinical isolates from preterm neonates and 5 American Tissue Culture Collection strains were characterized for their capacity to form biofilms in vitro, and antibiotic susceptibility was performed on each isolate prebiofilm and postbiofilm formation., Results: Forty-one (95%) clinical and 4 of 5 (80%) American Tissue Culture Collection isolates formed biofilms. All isolates were more susceptible to AZI (minimum inhibitory concentration, MIC50 2 µg/mL) than erythromycin (MIC50 4 µg/mL), and biofilm formation did not significantly affect antibiotic susceptibility for the 2 tested antibiotics. The MIC50 and minimum biofilm inhibitory concentrations (MBIC50) for Ureaplasma urealyticum clinical isolates for AZI were higher than for MIC50 and MBIC50 for Ureaplasma parvum isolates. There were no differences in MIC or MBICs among isolates from BPD infants and non-BPD infants., Conclusions: Capacity to form biofilms is common among Ureaplasma spp. isolates, but biofilm formation did not impact MICs for AZI or erythromycin.

Objective: To determine the prevalence of Ureaplasma urealyticum and Ureaplasma parvum bacteremia in very low birth weight (VLBW) infants and to evaluate the associated factors., Materials and Methods: Ninety-five VLBW newborns with gestational age ≤32 weeks were included in the study conducted between March 2009 and July 2010. DNA was extracted from the blood samples collected during the first 72 hours of life, and U. urealyticum and/or U. parvum were identified by polymerase chain reaction. The newborns were followed up until hospital discharge., Results: The prevalence of U. urealyticum and/or U. parvum bacteremia was 12.6% (12 cases): 5 (5.2%) for U. urealyticum, 5 (5.2%) for U. parvum, and 2 (2.1%) for both. Based on the univariate analysis, the presence of Ureaplasma was associated with clinical chorioamnionitis and spontaneous preterm labor. Preeclampsia and small for gestational age were associated with lower incidence of Ureaplasma. When spontaneous preterm labor was present, the prevalence of Ureaplasma bacteremia was 25%. Only spontaneous preterm labor was a statistically significant factor after step-by-step logistic regression analysis (P = 0.006), with 9-fold increase in chance of neonatal Ureaplasma bacteremia., Conclusions: Ureaplasma bacteremia is common in VLBW infants, especially among those born after preterm labor.

Objective: Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Whether the 4 Ureaplasma parvum and 10 Ureaplasma urealyticum serovars differ in virulence is unknown. This study was conducted to determine the distribution of Ureaplasma serovars in respiratory secretions of a prospective cohort of preterm infants and to assess whether any of the serovars are associated with BPD., Methods: Serial endotracheal and/or nasopharyngeal aspirates were obtained for Ureaplasma culture and PCR from 136 infants of gestational age <33 weeks. All positive samples were speciated and serovars were determined by real-time PCR., Results: A total of 51 (37.5%) infants were Ureaplasma-positive one or more times during the first month of life. Respiratory colonization was inversely related to gestational age. Sixty-five percent of infants <26 weeks compared with 31% infants ≥ 26 weeks were culture or PCR positive. U. parvum was more common (N = 32, 63%) than U. urealyticum (N = 17, 33%); both species were present in 2 samples. Serovars 3 and 6 alone and in combination accounted for 96% U. parvum isolates. U. urealyticum isolates were commonly a mixture of multiple serovars, with serovar 11 alone or combined with other serovars (10/17, 59%) being the most common serovar. No individual species or serovars or serovar mixtures were associated with moderate-to-severe BPD., Conclusions: U. parvum serovars 3 and 6 and U. urealyticum serovar 11 were the most common serovars detected in respiratory samples from a prospective cohort of preterm infants.

The significance of Ureaplasma species as pathogens in neonatal meningitis remains contentious. Using an illustrative case of a premature infant with Ureaplasma parvum meningitis, confirmed by cerebrospinal fluid cultures and both specific and 16s rDNA polymerase chain reaction, we discuss the epidemiology of Ureaplasma species, the difficulties involved in diagnosis and establishing pathogenicity, and the challenges in defining appropriate treatment.

Mollicutes can cause a wide spectrum of disease, especially in neonates. To better define their disease spectrum in the United States, we reviewed the results of >14,000 mollicute isolates, including 1346 from neonates. When mollicute infection is suspected, clinicians should alert laboratories, which will optimize methods of detection.

Background: Controversy exists over whether or not Ureaplasma colonization or infection of the respiratory tract contributes to the development of bronchopulmonary dysplasia (BPD). Because BPD is a major cause of morbidity and mortality in preterm infants and a potential therapeutic intervention with antimicrobials is possible, we sought to evaluate and critique the current medical literature and to document the reported association between Ureaplasma and BPD., Methods: We analyzed all peer-reviewed articles and previous reviews including cross-references that reported Ureaplasma respiratory tract colonization or infection and development of BPD in neonates published from January 1966 to December 2004. Inclusion criteria included a cohort limited to all neonatal intensive care unit admissions or all colonized infants, articles that did not define a numerator and a denominator for BPD and Ureaplasma or that included patients from other reports were excluded from the analysis. We evaluated BPD at 28 postnatal days (BPD28) or 36 weeks post-menstrual age (BPD36)., Results: Twenty-three studies with an aggregate of 2216 infants reported BPD28, and 8 studies with 751 infants reported BPD36. Although there was significant association between Ureaplasma colonization and both BPD28 and BPD36, there was substantial heterogeneity (Q test statistic, P < 0.01). We therefore focused on describing the study characteristics associated with an increased relative proportion of BPD. The greatest contribution to effect was from the studies enrolling fewer than 100 infants., Conclusion: Ureaplasma colonization is associated with higher reported rates of BPD, but the greatest reported effect is seen in small studies; reporting bias may be partially responsible for this effect.

We report an infant with a mixed Mycoplasma and Ureaplasma brain abscess who was successfully treated with intravenous doxycycline and erythromycin. Therapeutic concentrations of doxycycline were demonstrated in cerebrospinal fluid. This report is evidence of the potential for Mycoplasma and Ureaplasma to produce focal central nervous system infection, as well as meningitis, in neonates and that use of doxycycline can be efficacious in the therapy of such infections.

Objective: To describe the isolation of mycoplasmas and ureaplasmas from synovial fluid in pediatric patients with joint disorders., Methods: During 1 year 45 samples of synovial fluid, blood and urine were collected from 33 hospitalized pediatric patients up to 17 years old who had joint disorders. Mycoplasmas and ureaplasmas were isolated in joint fluid by culture methods., Results: Of the 33 patients 12 (36%) had joint disorders associated with pathogens (bacteria, Mycoplasma/Ureaplasma, Chlamydia) present at the site of inflammation. Mycoplasma hominis and Ureaplasma urealyticum were isolated from 3 and 1% of joint fluid samples, respectively. M. pneumoniae was isolated from nasopharyngeal secretion in a patient with evidence of a reactive arthritis., Conclusion: Our results raise the question of the possible role of Mycoplasma as a cofactor in the triggering of inflammatory joint disease, as well as the hypothesis that arthropathies may be caused by chronic local infection. These findings may contribute to early diagnosis of the disease and initiation of specific treatment.

The rates of colonization by Ureaplasma urealyticum and Mycoplasma hominis were evaluated in 208 women at delivery and in their neonates. Mycoplasmas were isolated from the cervicovaginal specimens of 100 mothers (48.1%) and from the gastric secretions of 40 neonates (19.2%). The prevalences of U. urealyticum and M. hominis were 47.6% and 11.0% in women and 19.2% and 1.0% in neonates, respectively. Premature rupture of membranes was significantly associated with colonization of women by U. urealyticum (P = 0.031), and colonization of their neonates by U. urealyticum (P = 0.002) and/or M. hominis (P = 0.023). Forty-four selected strains of mycoplasmas were further characterized by arbitrarily primed polymerase chain reaction. All strains of U. urealyticum belonged to the parvo biovar of the species. Arbitrarily primed polymerase chain reaction demonstrated the similarity of strains isolated from mother-neonate pairs, confirming the importance of vertical transmission of mycoplasmas at delivery.