Antenatal Ureaplasma Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies.

Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development.

Immunocompromised teenager with meningitis caused by Ureaplasma parvum.

Infection in the immunocompromised patient is often challenging on multiple levels. It can be difficult to distinguish between manifestations of the underlying disease, infection or malignancy. Symptoms may be vague or even absent, deviations in the common inflammatory parameters discrete, imaging findings scarce and the causative microbe may be a true pathogen as well as opportunistic. Here, we report an immunosuppressed female in her late teens with a purulent meningitis due to Ureaplasma parvum-a very rare cause of infection in the central nervous system of adults. We wish to highlight the relevance of intracellular pathogens and the need to actively search for these microbes, especially when response to broad-spectrum antibiotic treatment is absent. Furthermore, we emphasise the need for adequate molecular microbial diagnostics in search of microbes that are difficult to identify by culture and where serology and antigen tests may be absent or unreliable due to immune suppression.

Mycoplasma hominis increases the risk for Ureaplasma parvum infection in Human immunodeficiency virus infected pregnant women.

INTRODUCTION: Mycoplasma hominis and Ureaplasma parvum have been recently linked to sexually transmitted diseases and other conditions. There are a limited number of studies conducted on South African pregnant women that have assessed the prevalence and risk factors for genital mycoplasmas. METHODOLOGY: This study included 264 HIV infected pregnant women attending the King Edward VIII antenatal clinic in eThekwini, South Africa. DNA was extracted using the PureLink Microbiome kit and pathogens were detected using the TaqMan Real-time PCR assays. The statistical data analysis was conducted in a freely available Statistical Computing Environment, R software, version 3.6.3 using the RStudio platform. RESULTS: The prevalence of M. hominis and U. parvum, was 215/264 (81.4%), and 203/264 (76.9%), respectively. In the M. hominis positive group, a significantly (p = 0.004) higher proportion, 80.5% tested positive for U. parvum infection when compared to 61.2% among the M. hominis negative. Of the U. parvum positive women, a significantly (p = 0.004) higher proportion of women (85.2%) tested positive for M. hominis when compared to 68.9% among the U. parvum negative. In the unadjusted and adjusted analysis, being M. hominis positive increased the risk for U. parvum by approximately 3 times more (p = 0.014) and 4-fold (p = 0.008), respectively. CONCLUSIONS: This study showed a significant link between M. hominis and U. parvum infection. To date, there are a limited number of studies that have investigated M. hominisbeing a risk factor for U. parvum infection. Therefore, the data presented in the current study now fills in this gap in the literature.

Membrane inflammasome activation by choriodecidual Ureaplasma parvum infection without intra-amniotic infection in a Non-Human Primate model†.

Intrauterine infection is a significant cause of neonatal morbidity and mortality. Ureaplasma parvum is a microorganism commonly isolated from cases of preterm birth and preterm premature rupture of membranes (pPROM). However, the mechanisms of early stage ascending reproductive tract infection remain poorly understood. To examine inflammation in fetal (chorioamnionic) membranes we utilized a non-human primate (NHP) model of choriodecidual U. parvum infection. Eight chronically catheterized pregnant rhesus macaques underwent maternal-fetal catheterization surgery at ~105-112 days gestation and choriodecidual inoculation with U. parvum (105 CFU/mL, n =4) or sterile media (controls; n = 4) starting at 115-119 days, repeated at 5-day intervals until C-section at 136-140 days (term=167 days). The average inoculation to delivery interval was 21 days, and Ureaplasma infection of the amniotic fluid (AF) was undetectable in all animals. Choriodecidual Ureaplasma infection resulted in increased fetal membrane expression of MMP-9 and PTGS2, but did not result in preterm labor or increased concentrations of AF pro-inflammatory cytokines. However, membrane expression of inflammasome sensors, NLRP3, NLRC4, AIM2, and NOD2, and adaptor ASC (PYCARD) gene expression were significantly increased. Gene expression of IL-1ß, IL-18, IL-18R1  , CASPASE-1, and pro-CASPASE-1 protein increased with Ureaplasma infection. Downstream inflammatory genes MYD88 and NFκB (Nuclear factor kappa-light-chain-enhancer of activated B cells) were also significantly upregulated. These results demonstrate that choriodecidual Ureaplasma infection, can cause activation of inflammasome complexes and pathways associated with pPROM and preterm labor prior to microbes being detectable in the AF.

Effects of Ureaplasma parvum infection in the exosome biogenesis-related proteins in ectocervical epithelial cells.

Ureaplasma parvum is a mycoplasma commonly associated with female reproductive pathologies, such as preterm birth and infertility. It can survive intracellularly and utilize exosomes to propagate infection and its virulence factors. This study explored the differential protein composition of exosomes derived from normal and U. parvum-infected cells. We also investigated the impact of U. parvum on exosome biogenesis in ectocervical epithelial cells. Ectocervical epithelial (ECTO) cells were infected with U. parvum, and immunocytochemical staining was performed using U. parvum-specific marker multiple banded antigen (mba) and exosome marker CD9. NanoLC-MS/MS analysis was conducted to identify differentially expressed proteins in exosomes. Ingenuity Pathway Analysis (IPA) was performed to identify affected canonical pathways and biological functions associated with the protein cargo of exosomes. Western blot analysis of ECTO cells validated the proteomic findings in ECTO cells. U. parvum exhibited colonization of ECTO cells and colocalization with CD9-positive intraluminal vesicles. Proteomic analysis revealed decreased protein abundance and distinct protein profiles in exosomes derived from U. parvum-infected ECTO cells. Differentially expressed proteins were associated with clathrin-mediated endocytosis and various signaling pathways indicative of infection, inflammation, and cell death processes. Additionally, U. parvum infection altered proteins involved in exosome biogenesis. In ECTO cells, U. parvum infection significantly decreased clathrin, ALIX, CD9, and CD63 and significantly increased TSG101, Rab5, Rab35, and UGCG. These findings contribute to our understanding of the infection mechanism and shed light on the importance of exosome-mediated communication in the pathophysiology of diseases affecting the cervix, such as cervicitis and preterm birth.

Application of Metagenomic High-Throughput Sequencing in a Rare Case of Multisite Infection With Two Microorganisms After Total Knee Arthroplasty.

Postoperative deep infection is usually identified by microbial culture. However, frequent false-negative results have severely limited effective treatment. We report a rare case of intra-articular and paravertebral infection after total knee arthroplasty caused by Mycoplasma hominis and Ureaplasma urealyticum, with multiple negative microbial culture results. Eventually, the pathogens were identified using metagenomic high-throughput sequencing, and the patient was successfully treated with several "old" antibiotics. We analyze the clinical characteristics of this patient and systematically describe the application of high-throughput sequencing and antibiotics. [Orthopedics. 2024;47(1):e52-e56.].

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.

Trends of fluoroquinolones resistance in Mycoplasma and Ureaplasma urogenital isolates: Systematic review and meta-analysis.

BACKGROUND: Mycoplasma and Ureaplasma spp. especially M. hominis, U. parvum, and U. urealyticum recognized as an important cause of urogenital infections. Sake of the presence of antibiotic resistance and a continuous rise in resistance, the treatment options are limited, and treatment has become more challenging and costlier. OBJECTIVES: Therefore, this meta-analysis aimed to estimate worldwide resistance rates of genital Mycoplasmas and Ureaplasma to fluoroquinolones (ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin) agents. METHODS: We searched the relevant published studies in PubMed, Scopus, and Embase from until 3, March 2022. All statistical analyses were carried out using the statistical package R. RESULTS: The 30 studies included in the analysis were performed in 16 countries. In the metadata, the proportions of ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 59.8% (95% CI 49.6, 69.1), 31.2% (95% CI 23, 40), 7.3% (95% CI 1, 31), and 5.3% (95% CI 1, 2), respectively. According to the meta-regression, the ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin rate increased over time. There was a statistically significant difference in the fluoroquinolones resistance rates between different continents/countries (P < 0.05). CONCLUSIONS: Based on the results obtained in this systematic review and meta-analysis we recommend the use of the newer group of fluoroquinolones especially levofloxacin as the first choice for the treatment of genital mycoplasmosis, as well as ofloxacin for the treatment of genital infections caused by U. parvum.

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.

Severe Ureaplasma urealyticum infection in a patient with ocrelizumab-induced hypogammaglobulinaemia.

Infections caused by Ureaplasma urealyticum in immune-competent people are typically simple and uncomplicated. However, in cases of immunosuppression, severe disseminated infections can occur.This case report describes the case of a severe, disseminated infection caused by U. urealyticum in a young female with unacknowledged humoral immunosuppression due to treatment with ocrelizumab for multiple sclerosis.The patient was admitted due to a recurrent episode of a tubo-ovarian abscess. Throughout the following 2 months of hospitalisation, treatment with several types of antibiotics and the placement of various drains led to no improvement. As extensive investigations indicated hypogammaglobulinaemia, U. urealyticum was suspected, and tests came back positive. Treatment with doxycycline and moxifloxacin led to a full recovery.This demonstrates how humoral immunosuppression is a risk factor for severe disseminated infections and how these may be avoided through monitoring of immunoglobulin levels in patients treated with ocrelizumab.

Global analysis on the mutations associated with multidrug-resistant urogenital mycoplasmas and ureaplasmas infection: a systematic review and meta-analysis.

BACKGROUND: The emergence of multidrug-resistant (MDR) strains of genital pathogens, notably Mycoplasma genitalium and Ureaplasma spp., constitutes a significant global threat today. The present study aimed to evaluate the prevalence and trend of changes in MDR mycoplasma and ureaplasma strains. METHODS: An exhaustive search was performed across the ISI Web of Science, PubMed, Scopus, ScienceDirect, and Google Scholar databases to accumulate relevant studies without restrictions until April 2023. We used event rate and corresponding 95% confidence intervals to determine the frequency of resistance-related mutations and examine the trend of antibiotic resistance changes. RESULTS: The data from 27 studies, including 24,662 patients across 14 countries, were evaluated. Out of the total studies, 20 focused on M. genitalium infections, and five on Ureaplasma spp. The frequency of resistance-associated mutations to macrolides, tetracyclines, and fluoroquinolones in clinical strains of M. genitalium was 43.5%, 13.1%, and 18.6%, respectively. The prevalence of M. genitalium strains with double resistance and MDR was 11.0% and 17.4%, respectively. The incidence of both double-drug-resistant and MDR strains was higher in the World Health Organization (WHO) Western Pacific Region than in European and American populations. For Ureaplasma strains, resistance-associated mutations to macrolides, tetracyclines, and fluoroquinolones were 40.8%, 25.7%, and 90.3%, respectively. The rate of antibiotic resistance was higher in the African population compared to the European and WHO Western Pacific Regions. The rate of MDR Ureaplasma infections was 13.2%, with a higher incidence in the African population compared to the WHO Western Pacific and European regions. CONCLUSION: The proliferation and spread of MDR Mycoplasma and Ureaplasma strains present a significant public health challenge. The situation is indeed alarming, and the rising trend of MDR M. genitalium and MDR Ureaplasma infections suggests that therapies involving macrolides and fluoroquinolones may become less effective.

Association of Ureaplasma infection pattern and azithromycin treatment effect with bronchopulmonary dysplasia in Ureaplasma positive infants: a cohort study.

BACKGROUND: It is unclear whether Ureaplasma-associated pneumonia and azithromycin treatment affect the risk for bronchopulmonary dysplasia (BPD). METHODS: A retrospective cohort study was performed in very low birth weight (VLBW) infants who tested positive for Ureaplasma within 72 h after birth in a tertiary unit. Chest X-ray (CXR) and laboratory test were performed before and after azithromycin treatment. Multivariate logistic regression analysis was used to identify the independent association between BPD and Ureaplasma-associated pneumonia, as well as BPD and effective azithromycin treatment. RESULTS: A total of 118 infants were included in the current study, of whom 36 developed BPD (defined as supplemental oxygen needed at postmenstrual age 36 weeks or discharge). The rate of BPD was significantly higher in infants with Ureaplasma-associated pneumonia (44.6%) compared to infants with Ureaplasma colonization (17.7%, P = 0.002). After adjusting for confounders, an effective azithromycin treatment was significantly associated with reduced risk of BPD [odd ratio (OR) 0.011; 95% confidence interval (CI): 0.000-0.250), whereas Ureaplasma-associated pneumonia was not significantly associated with BPD (OR 1.835; 95% CI: 0.548-6.147). CONCLUSION: Effective Azithromycin treatment in Ureaplasma positive VLBW infants was associated with a reduced risk of BPD.

Disseminated Ureaplasma polyarthritis in a renal transplant recipient.

BACKGROUND: The risk of infection following kidney transplant increases substantially in the setting of hypogammaglobulinemia and T-cell-depleting therapy. Ureaplasma has been described to cause invasive disease in immunocompromised hosts with humoral immunodeficiency. We describe a kidney transplant recipient with history of antineutrophil cytoplasmic autoantibody (ANCA) vasculitis remotely treated with rituximab who developed Ureaplasma polyarthritis following transplant. The purpose of this report is to highlight the unique risks that kidney transplant patients face particularly if hypogammaglobulinemic. CASE REPORT: Patient is a 16-year-old female with history of granulomatosis with polyangiitis (GPA) treated with maintenance dose of rituximab 13 months prior to transplant. Patient underwent deceased donor kidney transplant with thymoglobulin induction. IgG was 332 mg/dL and CD20 was zero at the time of transplant. One month posttransplant, the patient developed polyarticular arthritis without fever, pyuria, or evidence of GPA reactivation. MRI had diffuse tenosynovitis, myositis, fasciitis, cellulitis, and effusions of three involved joints. Bacterial, fungal, and AFB cultures remained negative, but 16 s ribosomal PCR testing from joint aspirates detected Ureaplasma parvum. The patient was treated with levofloxacin for 12 weeks with the resolution of symptoms. CONCLUSIONS: Ureaplasma infection is an under-recognized pathogen in kidney transplant patients. A high index of clinical suspicion should be employed to identify Ureaplasma infection, especially in those with secondary hypogammaglobulinemia, as this is often missed due to its lack of growth on standard media and the need for molecular testing. In patients with prior B-cell depletion, routine monitoring for B-cell recovery to identify risk factors for opportunistic infections is indicated.

Next-generation sequencing-based detection of Ureaplasma in the gastric fluid of neonates with respiratory distress and chorioamnionitis.

BACKGROUND: Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress. OBJECTIVE: The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful. METHODS: Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed. RESULTS: Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B Streptococcus (Patient 15) and Candida albicans (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B Streptococcus from Patient 15. In the gastric fluid sample of Patient 24, Candida albicans were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster (Phormidium or Toxoplasma) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (Ureaplasma, Nostoc, and Streptococcus) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in Ureaplasma group than in the other two groups. CONCLUSION: Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of Ureaplasma in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for Ureaplasma in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings.

Effects of Ureaplasma urealyticum infection on semen quality and sperm morphology.

Introduction: Ureaplasma urealyticum (U. urealyticum) infection is primarily associated with damage to male fertility through its effects on male sperm parameters. However, its effects on sperm semiological variables remain unclear. Therefore, this study aimed to investigate whether U. urealyticum infection was associated with semen quality and sperm morphology. Methods: From 2019 to 2021, this cross-sectional study analyzed infective pathogens and semen variables in 1064 males (22-30 years old) recruited from our reproductive center and the general public. Routine semen parameters and normal sperm morphology rate were analyzed using methods outlined by the World Health Organization. The associations between semen quality, sperm morphology, and U. urealyticum infection were studied using general linear models. Results: The participants were categorized into three groups: (i) U. urealyticum infection (n=328), (ii) non-U. urealyticum infection (including males with urogenital tract infection symptoms but no U. urealyticum detected in their semen samples, n=377), and (iii) normal volunteers (males without symptoms of urogenital tract infection and no pathogens detected in semen samples, n=359). U. urealyticum in semen samples was observed to be associated with lower sperm concentrations (p<0.001) and a lower ratio of anterograde motile spermatozoa (p<0.001). Semen cultures positive for U. urealyticum were associated with lower normal sperm morphology (p<0.001) compared to semen cultures negative for U. urealyticum. Conclusion: This study shows the importance of proper investigations for U. urealyticum during routine clinical examinations and diagnoses of males with infertility.

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.

Efficacy of azithromycin in treating Ureaplasma urealyticum: a systematic review and meta-analysis.

BACKGROUND: Ureaplasma urealyticum is the most prevalent genital mycoplasma isolated from the urogenital tract of females, but there is no unified treatment plan. This study aimed to evaluate the efficacy of azithromycin in treating Ureaplasma urealyticum. METHODS: From the earliest to June 2022, published randomized controlled trials (RCTs) on azithromycin treatment of Ureaplasma urealyticum were retrieved by searching PubMed, Embase, Cochrane Library, and Web of Science. Two reviewers independently extracted the data. We utilized the Cochrane risk-of-bias assessment technique to assess the quality of included RCTs. The data were analyzed using the R language (version 4.0.4) software. RESULTS: Seven RCTs were finally included, involving 512 participants (240 in the experimental group, 272 in the control group). The experimental group was treated with azithromycin monotherapy, while the control group was treated with doxycycline or a placebo. Meta-analysis results suggested that azithromycin has a comparable therapeutic effect on Ureaplasma urealyticum in comparison to that of controls (risk ratio [RR] = 1.03, 95% confidence interval [CI] 0.94-1.12). Subgroup analysis showed that the dose and duration of azithromycin may don't affect its efficacy. CONCLUSION: Regarding the meta-analysis that we performed based on existing clinical studies, azithromycin is quite effective in treating Ureaplasma urealyticum.

Brain abscess with Ureaplasma parvum in a patient with granulomatosis with polyangiitis.

PURPOSE: Ureaplasma species are associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media with Ureaplasma parvum in a patient with granulomatosis with polyangiitis (GPA). METHODS: Imaging and laboratory findings, treatment decisions, and outcome of this case are explicated. RESULTS: A young adult with GPA presented with progredient earache after ambulant diagnosis of otitis media. Despite different courses of broad-spectrum antibiotic therapy, she developed meningoencephalitis due to mastoiditis following temporal abscess formation. Mastoidectomy and neurosurgical abscess removal were performed. Standard cultures of cerebrospinal fluid, blood and intracranial abscess material, as well as polymerase chain reaction (PCR) for common bacterial and viral meningitis pathogens remained negative. Only eubacterial PCR of intracranial abscess material returned positive for Ureaplasma parvum. The patient finally improved under antibiotic therapy with moxifloxacin and doxycycline. CONCLUSION: Ureaplasma species are rare causative pathogens in immunocompromised patients. They should be considered in patients with humoral immunodeficiencies with culture-negative infections failing standard therapy. Eubacterial PCR should be performed in early states of infection in these patients for immediate diagnosis and initiation of appropriate treatment to prevent adverse outcomes.

Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology.

Disruption of the intestinal mucus barrier and intestinal epithelial endoplasmic reticulum (ER) stress contribute to necrotizing enterocolitis (NEC). Previously, we observed intestinal goblet cell loss and increased intestinal epithelial ER stress following chorioamnionitis. Here, we investigated how chorioamnionitis affects goblet cells by assessing their cellular characteristics. Importantly, goblet cell features are compared with those in clinical NEC biopsies. Mucus thickness was assessed as read-out of goblet cell function. Fetal lambs were intra-amniotically (IA) infected for 7d at 122 gestational age with Ureaplasma parvum serovar-3, the main microorganism clinically associated with chorioamnionitis. After preterm delivery, mucus thickness, goblet cell numbers, gut inflammation, epithelial proliferation and apoptosis and intestinal epithelial ER stress were investigated in the terminal ileum. Next, goblet cell morphological alterations (TEM) were studied and compared to human NEC samples. Ileal mucus thickness and goblet cell numbers were elevated following IA UP exposure. Increased pro-apoptotic ER stress, detected by elevated CHOP-positive cell counts and disrupted organelle morphology of secretory cells in the intestinal epithelium, was observed in IA UP exposed animals. Importantly, comparable cellular morphological alterations were observed in the ileum from NEC patients. In conclusion, UP-driven chorioamnionitis leads to a thickened ileal mucus layer and mucus hypersecretion from goblet cells. Since this was associated with pro-apoptotic ER stress and organelle disruption, mucus barrier alterations seem to occur at the expense of goblet cell resilience and may therefore predispose to detrimental intestinal outcomes. The remarkable overlap of these in utero findings with observations in NEC patients underscores their clinical relevance.

Predicting the likelihood of lower respiratory tract Ureaplasma infection in preterms.

OBJECTIVE: To develop predictive models of Ureaplasma spp lower airway tract infection in preterm infants. METHODS: A dataset was assembled from five cohorts of infants born <33 weeks gestational age (GA) enrolled over 17 years (1999-2016) with culture and/or PCR-confirmed tracheal aspirate Ureaplasma status in the first week of life (n=415). Seventeen demographic, obstetric and neonatal factors were analysed including admission white blood cell (WBC) counts. Best subset regression was used to develop three risk scores for lower airway Ureaplasma infection: (1) including admission laboratory values, (2) excluding admission laboratory values and (3) using only data known prenatally. RESULTS: GA and rupture of membranes >72 hours were significant predictors in all 3 models. When all variables including admission laboratory values were included in the regression, WBC count was also predictive in the resulting model. When laboratory values were excluded, delivery route was found to be an additional predictive factor. The area under the curve for the receiver operating characteristic indicated high predictive ability of each model to identify infants with lower airway Ureaplasma infection (range 0.73-0.77). CONCLUSION: We developed predictive models based on clinical and limited laboratory information available in the perinatal period that can distinguish between low risk (<10%) and high risk (>40%) of lower airway Ureaplasma infection. These may be useful in the design of phase III trials of therapeutic interventions to prevent Ureaplasma-mediated lung disease in preterm infants and in clinical management of at-risk infants.