Risk factors, management, and clinical outcomes of invasive Mycoplasma and Ureaplasma infections after lung transplantation.

Mollicute infections, caused by Mycoplasma and Ureaplasma species, are serious complications after lung transplantation; however, understanding of the epidemiology and outcomes of these infections remains limited. We conducted a single-center retrospective study of 1156 consecutive lung transplants performed from 2010-2019. We used log-binomial regression to identify risk factors for infection and analyzed clinical management and outcomes. In total, 27 (2.3%) recipients developed mollicute infection. Donor characteristics independently associated with recipient infection were age ≤40 years (prevalence rate ratio [PRR] 2.6, 95% CI 1.0-6.9), White race (PRR 3.1, 95% CI 1.1-8.8), and purulent secretions on donor bronchoscopy (PRR 2.3, 95% CI 1.1-5.0). Median time to diagnosis was 16 days posttransplant (IQR: 11-26 days). Mollicute-infected recipients were significantly more likely to require prolonged ventilatory support (66.7% vs 21.4%), undergo dialysis (44.4% vs 6.3%), and remain hospitalized ≥30 days (70.4% vs 27.4%) after transplant. One-year posttransplant mortality in mollicute-infected recipients was 12/27 (44%), compared to 148/1129 (13%) in those without infection (P <.0001). Hyperammonemia syndrome occurred in 5/27 (19%) mollicute-infected recipients, of whom 3 (60%) died within 10 weeks posttransplant. This study highlights the morbidity and mortality associated with mollicute infection after lung transplantation and the need for better screening and management protocols.

Donor-derived Mycoplasma and Ureaplasma infections in lung transplant recipients: A prospective study of donor and recipient respiratory tract screening and recipient outcomes.

Mycoplasma hominis and Ureaplasma species are urogenital mollicutes that can cause serious donor-derived infections in lung transplant recipients. Best practices for mollicute screening remain unknown. We conducted a single-center prospective study analyzing lung transplants performed from October 5, 2020, to September 25, 2021, whereby donor and recipient bronchoalveolar lavage (BAL) samples obtained at time of transplant underwent mollicute screening via culture and polymerase chain reaction (PCR). Of 115 total lung transplants performed, 99 (86%) donors underwent combined mollicute BAL culture and PCR testing. The study cohort included these 99 donors and their matched recipients. In total, 18 (18%) of 99 donors screened positive via culture or PCR. Among recipients, 92 (93%) of 99 had perioperative BAL screening performed, and only 3 (3%) had positive results. After transplant, 9 (9%) recipients developed mollicute infection. Sensitivity of donor screening in predicting recipient mollicute infection was 67% (6/9) via culture and 56% (5/9) via PCR. Positive predictive value for donor culture was 75% (6/8), compared with 33% (5/15) for PCR. Donor screening via culture predicted all serious recipient mollicute infections and had better positive predictive value than PCR; however, neither screening test predicted all mollicute infections. Independent of screening results, clinicians should remain suspicious for posttransplant mollicute infection.

Ureaplasma infections: update on epidemiology, antimicrobial resistance, and pathogenesis.

Human Ureaplasma species are being increasingly recognized as opportunistic pathogens in human genitourinary tract infections, infertility, adverse pregnancy, neonatal morbidities, and other adult invasive infections. Although some general reviews have focused on the detection and clinical manifestations of Ureaplasma spp., the molecular epidemiology, antimicrobial resistance, and pathogenesis of Ureaplasma spp. have not been adequately explained. The purpose of this review is to offer valuable insights into the current understanding and future research perspectives of the molecular epidemiology, antimicrobial resistance, and pathogenesis of human Ureaplasma infections. This review summarizes the conventional culture and detection methods and the latest molecular identification technologies for Ureaplasma spp. We also reviewed the global prevalence and mechanisms of antibiotic resistance for Ureaplasma spp. Aside from regular antibiotics, novel antibiotics with outstanding in vitro antimicrobial activity against Ureaplasma spp. are described. Furthermore, we discussed the pathogenic mechanisms of Ureaplasma spp., including adhesion, proinflammatory effects, cytotoxicity, and immune escape effects, from the perspectives of pathology, related molecules, and genetics.

Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Prevalence of Ureaplasma species among patients at a tertiary hospital in China: a 10-year retrospective study from 2013 to 2022.

BACKGROUND: Ureaplasma species are common pathogens of the urogenital tract and can cause a range of diseases. Unfortunately, there is still a scarcity of large-scale and cross-sectional studies on the prevalence of Ureaplasma species in China to clarify their epidemic patterns. METHODS: This study retrospectively analyzed the data of 18667 patients who visited Peking Union Medical College Hospital for showing various symptoms of (suspected) Ureaplasma species infection during the period 2013-2022. The overall prevalence of Ureaplasma species was calculated, and subgroup analyses were conducted in view of gender, age, specimen types, and diagnosis in every year within the period studied. Furthermore, previous literature that reported on the prevalence of Ureaplasma species in various regions of China was searched and summarized. RESULTS: The overall positive rate of Ureaplasma species in this study reached 42.1% (7861/18667). Specifically, the prevalence of Ureaplasma species was significantly higher in female patients, while the highest detection rate was found in the 21-50 age group. From 2013 to 2022, there were no significant differences in positive rates of Ureaplasma species among years. However, the detection rate of Ureaplasma species was decreased in COVID-19 period (2020-2022) compared to pre-COVID-19 period (2017-2019). In view of the distribution of patients, outpatients predominated, but the detection rate was lower than inpatients. Urine was the most common specimen type, while cervical swabs had the highest detection rate of Ureaplasma species. When grouped by diagnosis, the highest positive rate of Ureaplasma species was seen in patients with adverse pregnancy outcomes and the lowest rate in patients with prostate disease. The previous literature, although heterogeneous, collectively suggested a high prevalence of Ureaplasma species in China. CONCLUSIONS: Our study has shown that Ureaplasma species have reached a significant prevalence in China and demands adequate attention.

Mycoplasma hominis and Ureaplasma urealyticum infections in the immediate post-lung transplant period: A case series and literature review.

Mycoplasma hominis and Ureaplasma species infections in the post-transplant setting are believed to be donor-derived and can be associated with poor outcomes. Difficulty in culturing and identifying these organisms is a significant barrier to diagnosis and early intervention. Tetracyclines, macrolides and fluoroquinolones are the mainstay treatments to cure these infections; however, there are increasing reports of antibiotic resistance. In this case series, we report our single-centre experience with M. hominis and U. urealyticum infection after lung transplantation (9 recipients, all men, mean age 56 years). Delayed diagnosis was common. Young donor age (mean age 23 yrs) and high-risk donor social history (67%) were repeatedly noted in these cases, and all infections were associated with significant morbidity (anastomosis and sternal wound infection, empyema, mediastinitis, pericarditis). Two patients died; with one directly related to Ureaplasma urealyticum infection. In conclusion post lung transplant M. hominis, and U. urealyticum infections are challenging and carry high morbidity. More prospective studies are required to assess the true prevalence, full spectrum of complications and utility of molecular diagnostics to aid early diagnosis and identify antibiotic susceptibility of Mycoplasma and Ureaplasma infections in the post-lung transplant setting.

Prevalence and Antimicrobial Susceptibility of Mycoplasma hominis and Ureaplasma Species in Nonpregnant Female Patients in South Korea Indicate an Increasing Trend of Pristinamycin-Resistant Isolates.

Mycoplasma hominis and Ureaplasma species, commonly found in the lower urogenital tract, have been associated with various urogenital infections. This study aimed to estimate the prevalence and antimicrobial susceptibility trend of M. hominis and Ureaplasma sp. in female patients and to evaluate the risk factors for the acquisition of pristinamycin-resistant mycoplasma. Endocervical swab specimens obtained between March 2016 and December 2018 were analyzed using a Mycoplasma IST2 kit. Because pristinamycin and josamycin are not available in South Korea, we conducted an age- and date-matched case-control study to evaluate the risk factors for the acquisition of pristinamycin-resistant isolates. Among 4,035 specimens, 1,589 (39.4%) cases were positive for genital mycoplasma, which included 49 (3.1%) cases of M. hominis, 1,243 (78.2%) cases of Ureaplasma sp., and 297 (18.7%) cases of both M. hominis and Ureaplasma species. Based on antimicrobial susceptibility tests, the antibiotic susceptible rate of both M. hominis and Ureaplasma species to pristinamycin decreased annually during the study period (100%, 97.1%, and 87.3% for 2016, 2017, and 2018, respectively, P < 0.001). According to a multivariate analysis, josamycin resistance (odds ratio, 7.18; 95% confidence interval, 1.20 to 43.00; P = 0.027) and coinfection (odds ratio, 145.38; 95% confidence interval, 21.80 to 3,017.23; P < 0.001) with Candida species were independent risk factors for the acquisition of pristinamycin-resistant isolates. Antibiotic-resistant genital mycoplasmas have been gradually increasing annually. Nationwide surveillance, proper antibiotic stewardship, and appropriate culture-based treatment strategies are required to control this upcoming threat.

Antimicrobial resistance, genetic characterization, and molecular epidemiology of Ureaplasma species in males with infertility.

This study aimed to study the antimicrobial resistance, genetic characterization, and molecular epidemiology of Ureaplasma species in order to provide clinicians sufficient data to select optimal strategies of treatment for genitourinary tract infections of infertile male patients. Firstly, a total of 817 clinical semen specimens were detected for Ureaplasma species by molecular detection. Secondly, culture and identification of Ureaplasma species were achieved by using Mycoplasma ICS Test, and the antimicrobial susceptibility tests were determined by using broth microdilution assay. Then, the tetracycline resistance genetic determinants in Ureaplasma species were identified by PCR, and the fluoroquinolone and macrolide resistance genetic determinants were identified by DNA sequencing. Finally, the molecular epidemiology of Ureaplasma species was studied by both multilocus sequence typing (MLST) and expanded MLST (eMLST) schemes. Among the 817 semen specimens, 320 (39.17%) specimens were positive for Ureaplasma species. The percentages of resistance in 320 isolates against LEV, MXF, TET, and ERY were 47.5%, 39.38%, 19.69%, and 3.75%, respectively. The tet(M) and int-Tn genes were detected positive in all the tetracycline-resistant isolates. One macrolide-resistant UU isolate had a novel amino acid alteration (R66T) in L4 ribosomal protein and another UU isolate harbored a novel alteration (S109T) in L22. In fluoroquinolone-resistant isolates, S83L substitution in the ParC was predominant. In this area, ST22 and eST16 were the most prevalent ST and eST, respectively. One ST and 3 eSTs were newly identified in this study. This study has demonstrated that ERY can be first-line therapy for Ureaplasma species infections.

Novel insights into neuroinflammation: bacterial lipopolysaccharide, tumor necrosis factor α, and Ureaplasma species differentially modulate atypical chemokine receptor 3 responses in human brain microvascular endothelial cells.

BACKGROUND: Atypical chemokine receptor 3 (ACKR3, synonym CXCR7) is increasingly considered relevant in neuroinflammatory conditions, in which its upregulation contributes to compromised endothelial barrier function and may ultimately allow inflammatory brain injury. While an impact of ACKR3 has been recognized in several neurological autoimmune diseases, neuroinflammation may also result from infectious agents, including Ureaplasma species (spp.). Although commonly regarded as commensals of the adult urogenital tract, Ureaplasma spp. may cause invasive infections in immunocompromised adults as well as in neonates and appear to be relevant pathogens in neonatal meningitis. Nonetheless, clinical and in vitro data on Ureaplasma-induced inflammation are scarce. METHODS: We established a cell culture model of Ureaplasma meningitis, aiming to analyze ACKR3 variances as a possible pathomechanism in Ureaplasma-associated neuroinflammation. Non-immortalized human brain microvascular endothelial cells (HBMEC) were exposed to bacterial lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α), and native as well as LPS-primed HBMEC were cultured with Ureaplasma urealyticum serovar 8 (Uu8) and U. parvum serovar 3 (Up3). ACKR3 responses were assessed via qRT-PCR, RNA sequencing, flow cytometry, and immunocytochemistry. RESULTS: LPS, TNF-α, and Ureaplasma spp. influenced ACKR3 expression in HBMEC. LPS and TNF-α significantly induced ACKR3 mRNA expression (p < 0.001, vs. control), whereas Ureaplasma spp. enhanced ACKR3 protein expression in HBMEC (p < 0.01, vs. broth control). Co-stimulation with LPS and either Ureaplasma isolate intensified ACKR3 responses (p < 0.05, vs. LPS). Furthermore, stimulation wielded a differential influence on the receptor's ligands. CONCLUSIONS: We introduce an in vitro model of Ureaplasma meningitis. We are able to demonstrate a pro-inflammatory capacity of Ureaplasma spp. in native and, even more so, in LPS-primed HBMEC, underlining their clinical relevance particularly in a setting of co-infection. Furthermore, our data may indicate a novel role for ACKR3, with an impact not limited to auto-inflammatory diseases, but extending to infection-related neuroinflammation as well. AKCR3-induced blood-brain barrier breakdown might constitute a potential common pathomechanism.

Vaginal Ureaplasma species increase chorioamnionitis in very preterm infants with preterm premature rupture of the membranes at < 28 weeks of gestation.

Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subsequent occurrence of chorioamnionitis (CAM), perinatal death, neonatal morbidity, and long-term neurodevelopmental impairments (NDIs) at 3 years of age. We analyzed 55 pregnant women with singleton pregnancy who had preterm premature rupture of the membranes (pPROM) at < 28+0 weeks of gestation, and delivered between 22+0 and 31+6 weeks at our tertiary hospital in 2007-2016. NDIs were defined as either cerebral palsy or developmental delay evaluated at 1.5 and/or 3 years old. The presence of Ureaplasma spp. and Mycoplasma hominis were evaluated using urea-arginine broth and Mycoplasma PPLO Agar. The presence of Ureaplasma spp. in the vagina was positive in 41%. Vaginal Ureaplasma spp. was a significant risk factor for CAM; however, it was not significantly associated with the occurrence of perinatal death, pulmonary hypoplasia, respiratory distress syndrome, transient tachypnea of the newborn, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia defined as oxygen required and occasional ventilatory assistance required at week 36 as modified (BPD36), or NDIs. The crude odds ratio (95% confidence interval) of Ureaplasma spp. for the occurrence of CAM was 9.5 (1.10-82) (p = 0.041). In very preterm birth infants with pPROM, CAM, BPD36, and NDIs occurred in 78, 60, and 36%, respectively. Vaginal Ureaplasma spp. was a significant risk factor for CAM in very preterm birth infants with pPROM. The incidences of BPD36 and NDIs in such infants were very high, nearing 3/5 and 1/3, respectively.

Placental Infection With Ureaplasma species Is Associated With Histologic Chorioamnionitis and Adverse Outcomes in Moderately Preterm and Late-Preterm Infants.

OBJECTIVE: The human Ureaplasma species are the microbes most frequently isolated from placentae of women who deliver preterm. The role of Ureaplasma species has been investigated in pregnancies at <32 weeks of gestation, but currently no studies have determined the prevalence of ureaplasmas in moderately preterm and late-preterm (hereafter, "moderate/late preterm") infants, the largest cohort of preterm infants. METHODS: Women delivering moderate/late preterm infants (n = 477) and their infants/placentae (n = 535) were recruited, and swab specimens of chorioamnion tissue, chorioamnion tissue specimens, and cord blood specimens were obtained at delivery. Swab and tissue specimens were cultured and analyzed by 16S ribosomal RNA polymerase chain reaction (PCR) for the presence of microorganisms, while cord blood specimens were analyzed for the presence of cytokines, chemokines, and growth factors. RESULTS: We detected microorganisms in 10.6% of 535 placentae (443 were delivered late preterm and 92 were delivered at term). Significantly, Ureaplasma species were the most prevalent microorganisms, and their presence alone was associated with histologically confirmed chorioamnionitis in moderate/late preterm and term placentae (P < .001). The presence of ureaplasmas in the chorioamnion was also associated with elevated levels of granulocyte colony-stimulating factor (P = .02). CONCLUSIONS: These findings have important implications for infection and adverse pregnancy outcomes throughout gestation and should be of major consideration for obstetricians and neonatologists.

Intrauterine Detection of Ureaplasma Species after Vaginal Colonization in Pregnancy and Neonatal Outcome.

INTRODUCTION: Intrauterine infection with Ureaplasma species (U.spp.) is mostly a result of vaginal colonization with subsequent ascending infection and is associated with adverse pregnancy outcome. Little is known about rates and risk factors for ascending infection. Aim of the current study was to analyse the frequency of ascending U.spp. infection in vaginally colonized pregnant women delivering preterm and subsequent short- and long-term outcome of infants. METHODS: Women delivering ≤32 weeks of gestation with available data on vaginal U.spp. colonization in early pregnancy as well as amniotic and placental colonization screening during caesarean section were included. Neonatal short- and long-term outcome was analysed depending on vaginal and intrauterine colonization. RESULTS: Seventy-two women giving birth to 104 preterm infants were included. Intrauterine microbial invasion was found in 23/72 (31.9%) pregnancies. The most commonly detected organisms were U.spp. (52.2%), followed by E. coli (21.7%) and Enterococcus faecalis (17.4%). Intrauterine growth of U.spp. occurred exclusively after previous vaginal colonization in early pregnancy (42/72; 58.3%) and was found in 12/42 (28.6%) cases. Ascending U.spp. infection mainly occurred in pregnancies delivering <28 weeks after preterm rupture of membranes or preterm labour (9/17, 52.3%). Intrauterine detection of U.spp., but not vaginal colonization, was associated with a significantly higher rate of severe intraventricular haemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and unfavourable psychomotor outcome. CONCLUSION: Ascending U.spp. infection after previous vaginal colonization occurred in almost one-third of pregnancies delivering ≤32 weeks, with particularly high rates in those <28 weeks, and was associated with adverse outcome of preterm infants.

The Role of Ureaplasma Species in Prenatal and Postnatal Morbidity of Preterm Infants: Current Concepts.

BACKGROUND: Ureaplasma species are considered commensals of the adult urogenital tract. Yet, in pregnancy, Ureaplasma parvum and Ureaplasma urealyticum have been associated with chorioamnionitis and preterm birth. In preterm infants, Ureaplasma respiratory tract colonization has been correlated with the development of bronchopulmonary dysplasia and has been implicated in the pathogenesis of other complications of prematurity. Controversies on the impact of Ureaplasma exposure on neonatal morbidity, however, remain, and recommendations for screening practices and therapeutic management in preterm infants are missing. SUMMARY: In this review, we outline clinical and experimental evidence of Ureaplasma-driven fetal and neonatal morbidity, critically examining inconsistencies across some of the existing studies. We explore underlying mechanisms of Ureaplasma-associated neonatal morbidity and discuss gaps in the current understanding including the interplay between Ureaplasma and the maternal urogenital tract and the preterm airway microbiome. Ultimately, we highlight the importance of adequate diagnostics and review the potential efficacy of anti-infective therapies. KEY MESSAGES: There is strong evidence that perinatal Ureaplasma exposure is causally related to the development of bronchopulmonary dysplasia, and there are conclusive data of the role of Ureaplasma in the pathogenesis of neonatal central nervous system infection. Observational and experimental findings indicate immunomodulatory capacities that might promote an increased risk of secondary infections. The burden of Ureaplasma exposure is inversely related to gestational age - leaving the tiniest babies at highest risk. A better knowledge of contributing pathogen and host factors and modulating conditions remains paramount to define screening and treatment recommendations allowing early intervention in preterm infants at risk.

Genital infection with Ureaplasma urealyticum and its effect on pregnancy.

Chorioamnionitis or intra-amniotic infection is an infection that affects the intrauterine content during pregnancy. Numerous studies have reported vaginal colonization with various types of infectious agents as a risk factor for chorioamnionitis. Although this complication occurs due to the ascending polymicrobial bacterial infection at the time of membrane breakage, it may also occur in pregnant women with intact membranes, mainly due to Ureaplasma urealyticum (U. urealyticum) and Mycoplasma hominis (M. hominis). The main aim of the present study was to identify a region-specific panel of infectious agents that can be used more accurately determine premature birth, as well as the premature rupture of membranes (PROM). Thus, a 10-year retrospective study was conducted. A total of 1,301 pregnant women with PROM and premature birth or spontaneous abortion were included in the study. It was observed that the main infectious agent varied in the five groups analyzed in total. The infectious agent distribution also varied depending on environmental parameters. Ureaplasma was found to be the most frequently detected germ amongst the infectious agents of the vaginal cultures from pregnant women enrolled in the present study, regardless of gestational age. On the whole, the findings of the present study suggest that additional studies are required, in order to confirm that diagnosis and treatment according to laboratory results of vaginal infections with U. urealyticum/M. hominis during the first trimester of pregnancy could prevent premature birth, abortion or chorioamnionitis.

Genital Mycoplasmas and Biomarkers of Inflammation and Their Association With Spontaneous Preterm Birth and Preterm Prelabor Rupture of Membranes: A Systematic Review and Meta-Analysis.

Genital mycoplasmas (GM), such as Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma parvum, and Ureaplasma urealyticum are commonly associated with spontaneous preterm labor (SPTL), spontaneous preterm birth (PTB), and preterm prelabor rupture of membranes (PPROM). This study determined the association between GM and such adverse pregnancy outcomes. We searched for studies published 1980-2019 in MEDLINE, EMBASE, and Web of Science. Studies were eligible when GM was detected during pregnancy. We included 93 and 51 studies in determining the prevalence and the inflammatory biomarkers associated with GM, respectively, using the "metafor" package within R. The protocol was registered with PROSPERO (registration no. CRD42016047297). Women with the studied adverse pregnancy outcomes had significantly higher odds of presence with GM compared to women who delivered at term. For PTB, the odds ratios were: M. hominis (OR: 2.25; CI: 1.35-3.75; I 2: 44%), M. genitalium (OR: 2.04; CIL 1.18-3.53; I 2: 20%), U. parvum (OR: 1.75; CI: 1.47-2.07; I 2: 0%), U. urealyticum (OR: 1.50; CI: 1.08-2.07; I 2: 58%). SPTL had significantly higher odds with M. hominis (OR: 1.96; CI: 1.19-3.23; I 2: 1%) or U. urealyticum (OR: 2.37; CI: 1.20-4.70; I 2: 76%) compared to women without SPTL. Women with PPROM had significantly higher odds with M. hominis (OR: 2.09; CI: 1.42-3.08; I 2: 0%) than women without PPROM. However, our subgroup analysis based on the diagnostic test and the sample used for detecting GM showed a higher prevalence of GM in maternal samples than in fetal samples. GM presence of the cervix and vagina was associated with lower odds of PTB and preterm labor (PTL). In contrast, GM presence in the AF, fetal membrane, and placenta was associated with increased odds of PTB and PTL. However, genital mycoplasmas may not elicit the massive inflammation required to trigger PTB. In conclusion, GM presence in the fetal tissues was associated with significantly increased odds of PTB and PTL.

Different degrees of maternal Ureaplasma colonization and its correlation with bronchopulmonary dysplasia in <32 weeks' preterm infants.

BACKGROUND: Ureaplasma spp. is a known risk factor for bronchopulmonary dysplasia (BPD). However, little is known about the effect of different degrees of maternal Ureaplasma colonization and their adverse outcomes. Hence, the aim of this study was to determine the effects of different degrees of maternal Ureaplasma colonization on BPD. METHODS: A retrospective cohort study of preterm infants delivered at <32 weeks' gestational age (GA) was performed. The infants were divided according to maternal Ureaplasma status as follows: high-colonization (≥104 CCU/ml, UUH), low-colonization (<104 CCU/ml, UUL), and noncolonization (controls). Subgroup analysis according to neonatal respiratory Ureaplasma (n-UU) was also performed to evaluate vertical transmission. RESULTS: In total, 245 infants were included in this study (UUH = 105, UUL = 47, controls = 93). The rates of preterm labor and histological chorioamnionitis were significantly different. The rate of BPD was significantly high in UUH (P = 0.044). The transmission rate of n-UU colonization was 36% in UUH and 32% in UUL (P = 0.609). The rate of BPD was 78% in n-UU (+) of UUH but 43% in n-UU (-) of UUL (P = 0.027). CONCLUSIONS: High-degree colonization of maternal Ureaplasma was associated with preterm labor, histological chorioamnionitis, and neonatal BPD. The incidence of BPD was significantly higher in Ureaplasma-colonized infants born to women with high-degree colonization.

Rapid and simple detection of Ureaplasma species from vaginal swab samples using a loop-mediated isothermal amplification method.

PROBLEM: Ureaplasma species occasionally cause chorioamnionitis and premature labor. We developed a novel assay employing a loop-mediated isothermal amplification (LAMP) method to detect Ureaplasma parvum and Ureaplasma urealyticum. METHOD OF STUDY: Loop-mediated isothermal amplification primers were designed to amplify Ureaplasma-specific ureaseB genes. Four U. parvum strains, 5 U. urealyticum strains and 14 reference bacterial species were evaluated. Forty-six vaginal swab samples were analyzed by LAMP, culture, and PCR. RESULTS: Our LAMP primers were specific to each species and had no cross-reaction. Of 46 clinical specimens, the sensitivity, specificity, and positive and negative predictive values of the LAMP method were 100% (12/12), 100% (34/34), 100% (12/12), and 100% (34/34), respectively, whereas those of PCR were 66.7% (8/12), 100% (34/34), 100% (8/8), and 89.5% (34/38), respectively, compared to culture-based detection. CONCLUSION: The LAMP detection method outperformed the culture and PCR methods. Early detection enables appropriate antibiotic selection for improved prenatal outcomes.

Mollicutes in vaginal microbiology: Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma genitalium.

Mycoplasma hominis was isolated in 1937 from the human genital tract, followed 17 years later by Ureaplasma urealyticum and 27 years after that by Mycoplasma genitalium. The first two proved relatively easy to culture but the latter required a polymerase chain reaction assay for further studies. In sexually mature women, M. hominis may be found in the vagina/cervix of about 20-50%, ureaplasmas in 40-80% and M. genitalium in 0-5%. Some heterogeneity has been found among strains of all these species, sufficient to divide ureaplasmas into two species, namely U. urealyticum and Ureaplasma parvum. Studies in female mice show that sex hormones have a profound influence on colonization, multiplication and persistence of mycoplasmas/ureaplasmas in the genital tract and provoke the question, unanswered, of whether there is such an effect in the human tract. In women, there is no evidence that any of the mycoplasmal species stimulate an inflammatory vaginitis. M. hominis organisms increase hugely in number in the case of bacterial vaginosis (BV), and to a lesser extent so do ureaplasmas. Despite this, they have not been incriminated as a sole cause of BV. Evidence for the involvement of M. genitalium remains controversial. The strong association of BV with preterm birth raises the possibility that the genital mycoplasmas might play a part, but assurance that any do will be difficult to obtain. Detailed examination of the vaginal microbiome has not yet provided an answer.

Anti-inflammatory effects of the new generation synthetic surfactant CHF5633 on Ureaplasma-induced cytokine responses in human monocytes.

BACKGROUND: Synthetic surfactants represent a promising alternative to animal-derived preparations in the treatment of neonatal respiratory distress syndrome. The synthetic surfactant CHF5633 has proven biophysical effectiveness and, moreover, demonstrated anti-inflammatory effects in LPS-stimulated monocytes. With ureaplasmas being relevant pathogens in preterm lung inflammation, the present study addressed immunomodulatory features on Ureaplasma-induced monocyte cytokine responses. METHODS: Ureaplasma parvum-stimulated monocytes were exposed to CHF5633. TNF-α, IL-1ß, IL-8, IL-10, TLR2 and TLR4 expression were analyzed using qPCR and flow cytometry. RESULTS: CHF5633 did not induce pro-inflammation, and did not aggravate Ureaplasma-induced pro-inflammatory cytokine responses. It suppressed U. parvum-induced intracellular TNF-α (p < 0.05) and IL-1ß (p < 0.05) in neonatal monocytes and inhibited Ureaplasma-induced TNF-α mRNA (p < 0.05), TNF-α protein (p < 0.001), and IL-1ß (p = 0.05) in adult monocytes. Ureaplasma-modulated IL-8, IL-10, TLR2 and TLR4 were unaffected. CONCLUSION: CHF5633 does neither act pro-apoptotic nor pro-inflammatory in native and Ureaplasma-infected monocytes. Suppression of Ureaplasma-induced TNF-α and IL-1ß underlines anti-inflammatory features of CHF5633.

Ureaplasma Species Multiple Banded Antigen (MBA) Variation Is Associated with the Severity of Inflammation In vivo and In vitro in Human Placentae.

Background: The multiple banded antigen (MBA), a surface-exposed lipoprotein, is a proposed virulence factor of Ureaplasma spp. We previously demonstrated that the number of Ureaplasma parvum MBA size variants in amniotic fluid was inversely proportional to the severity of chorioamnionitis in experimentally infected pregnant sheep. However, the effect of ureaplasma MBA size variation on inflammation in human pregnancies has not been reported. Methods: Ureaplasmas isolated from the chorioamnion of pregnant women from a previous study (n = 42) were speciated/serotyped and MBA size variation was demonstrated by PCR and western blot. Results were correlated with the severity of chorioamnionitis and cord blood cytokines. In vitro, THP-1-derived macrophages were exposed to recombinant-MBA proteins of differing sizes and NF-κB activation and cytokine responses were determined. Results: MBA size variation was identified in 21/32 (65.6%) clinical isolates (in 10 clinical isolates MBA size variation was unable to be determined). Any size variation (increase/decrease) of the MBA (regardless of Ureaplasma species or serovar) was associated with mild or absent chorioamnionitis (P = 0.023) and lower concentrations of cord blood cytokines IL-8 (P = 0.04) and G-CSF (P = 0.008). In vitro, recombinant-MBA variants elicited different cytokine responses and altered expression of NF-κB p65. Conclusion: This study demonstrates that size variation of the ureaplasma MBA protein modulates the host immune response in vivo and in vitro.