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Ureaplasma urealyticum and Mycoplasma hominis are common inhabitants of the human genital tract. Increasingly, serious and sometimes fatal infections in immunocompromised hosts have been reported, highlighting their pathogenic potential. We reviewed the clinical impact of positive Ureaplasma spp. and Mycoplasma spp. urine cultures in 10 renal allograft recipients who presented with sterile leukocyturia. Five recipients remained asymptomatic. Five patients were symptomatic with dysuria or pain at the graft site. Three patients developed biopsy-proven acute graft pyelonephritis with graft dysfunction. One of these patients additionally showed a renal abscess as demonstrated by magnetic resonance imaging (MRI). All were successfully treated. A literature search revealed a substantial number of case reports with severe and sometimes fatal Ureaplasma spp. or Mycoplasma spp. infections in immunocompromised patients. Colonization rate is high in renal transplant patients. A subset of patients is at risk for invasive disease., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 17-year-old male with acute lymphoblastic leukemia developed severe hematuria and scrotal swelling after haploidentical hematopoietic cell transplantation (HCT). Urine culture was negative. BK virus and adenovirus were negative. However, Ureaplasma urealyticum was detected. He showed dramatic improvement after doxycycline treatment. This is the first report in the literature of hemorrhagic cystitis caused by U. urealyticum in a HCT recipient. In HCT recipients with hemorrhagic cystitis, U. urealyticum should be considered as a potential cause., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: This study explored chlamydia trachomatis (CT), ureaplasma urealyticum (UU) and/or neisseria gonorrhoeae (NG) in 5893 women with urinary tract infections (UTIs) in Shanghai., Methods: From January 2009 to December 2014, 5893 women with UTIs in Shanghai were selected to undergo CT, UU and NG detection. Baseline characteristics including age, education level, occupation, reproductive history, sexual behavior and contraceptive method were obtained for epidemiological analysis., Results: The total CT, UU and/or NG infection rate in the urine samples of 5893 patients was 50.69% (2987/5893), while the infection rate in vaginal secretion samples was 56.22% (3313/5893). The two detection methods were consistent. Patients aged 21-30, service personnel and unemployed persons had the highest rates of CT, UU and/or NG infection, while patients with higher education levels exhibited lower rates. As the number of previous pregnancies, natural births, abortions, sexual partners and the frequency of sexual intercourse increased, the rates of CT, UU and/or NG infection were elevated. Sexual intercourse during the menstruation period, a lack of cleaning before sexual intercourse and the use of intrauterine devices could all lead to an increased rate of CT, UU and/or NG infection., Conclusions: These data revealed that the rate of CT, UU and/or NG infection may be associated with age, education level, occupation, reproductive history, sexual behavior and type of contraceptive method in female patients with UTI in Shanghai., (© 2017 Japan Society of Obstetrics and Gynecology.)

The article presents current views on urogenital diseases caused by M. hominis and U. urealyticum. Particular attention is paid to concurrent (co-occurring) urogenital infections. The review reports the data from epidemiological studies and outlines recent Russian and international guidelines and consensuses on managing patients with urogenital inflammatory diseases. The importance of adequate diagnosis and rational therapy of urogenital infections is discussed.

Genital tract infections with ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) are the most frequent sexually-transmitted disease worldwide. UU and CT infections are considered to be the leading cause for infertility and adverse pregnancy outcomes. However, little is known about the specific effect of cervical UU and CT infections on the etiology of female infertility, as well as the pregnancy outcomes of the patients undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). In order to find the association between cervical UU and/or CT infection and pregnancy outcomes, we conducted a retrospective case-control study on the patients undergoing IVF/ICSI-ET with cervical UU and/or CT infection. A total of 2208 patients who received IVF/ICSI-ET were enrolled in this study. Data on the general conditions, pregnancy history and clinical pregnant outcomes were analyzed in terms of the cervical UU and CT detection. Our results revealed that cervical UU and CT infections were the risk factors for ectopic pregnancy and tubal factor-induced infertility. Moreover, the pregnancy rate, abortion rate, ectopic pregnancy rate and premature birth rate in patients with UU and/or CT infections showed no significant difference when compared with the control group. We recommend that cervical UU and CT detection should be an optional item for infertility patients and clinical UU detection should differentiate the subtypes of cervical UU. Positive cervical UU and CT infections should not be taken as strict contraindications for IVF/ICSI-ET.

Ureaplasma urealyticum is an opportunistic pathogen during pregnancy and in newborns. Other clinical problems related to U. urealyticum infections are: no susceptibility to cell wall-active drugs, limits of antibiotic treatment in pregnancy, and spread of antimicrobial resistance. In addition, the results of antimicrobial susceptibility against U. urealyticum from various countries are few and controversial. The antimicrobial susceptibility of U. urealyticum, isolated from cervical swabs and collected from outpatient childbearing-aged women in Italy from 2009 to 2012, was performed against fluoroquinolones, macrolides, streptogramin and tetracyclines, using an available biochemical commercial kit and a specific solid culture medium, to improve the therapeutic management of these pathogenic agents. Ureaplasma urealyticum was detected in 49.4% of samples, but significant bacterial load was revealed in 29.8%. In vitro tetracyclines showed the best activity against U. urealyticum, followed by streptogramin, macrolides, and fluoroquinolones., (© 2013 APMIS. Published by John Wiley & Sons Ltd.)

There is controversy regarding the roles of Ureaplasma urealyticum (U. urealyticum) colonization in the development of bronchopulmonary dysplasia (BPD). This study explored the association between U. urealyticum and bronchopulmonary dysplasia at 36 weeks post-menstrual age (BPD36). Studies published before December 31, 2013 were searched from Medline, Embase, Ovid, Web of Science, and Cochrane databases, with the terms "Ureaplasma urealyticum", "chronic lung disease", or "BPD36" used, and English language as a limit. The association between U. urealyticum colonization and BPD36 was analyzed with RevMan 4.2.10 software, using the odds ratio (OR) and relative risk (RR) for dichotomous variables. Out of the enrolled 81 studies, 11 investigated the BPD36 in total 1193 infants. Pooled studies showed no association between U. urealyticum colonization and subsequent development of BPD36, with the OR and RR being 1.03 (95% CI=0.78-1.37; P=0.84) and 1.01 (95% CI= 0.88-1.16, P=0.84), respectively. These findings indicated no association between U. urealyticum colonization and the development of BPD36.

Objective: To explore the distribution of Ureaplasma urealyticum (UU) serotypes in cervix secretion and examine the relationship between serotype and host age, clinical phenotypes and vaginal Lactobacilli., Methods: A total of 444 cervical secretion samples were collected from healthy subjects and 342 cervical secretion samples from females with genital diseases between October and December 2012 at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Biovar-typing was performed by PCR based on multiple-banded antigen (MBA) gene. And serotyping was performed by real-time PCR based on specific nucleotide sequences., Results: The positive rate of UU in disease group (62.6%, 214/342) was significantly higher than that in healthy group (44.1%, 196/444, P < 0.05). The main serotypes in both groups were 1, 3, 6, 9 and mixed infection.No significant difference existed between host age and UU serotype (P > 0.05) . The distribution of serotype 3 in disease and Lactobacilli abnormal group was significantly higher than that in healthy and Lactobacilli normal groups (13.1% (28/214) vs 5.1% (10/196) , 12.2% (27/221) vs 5.8% (11/189) , both P < 0.05) whereas the distribution of serotype 6 in disease and Lactobacilli abnormal groups was significantly lower than that in healthy and Lactobacilli normal groups (14.0% (30/214) vs 30.1% (59/196) , 16.3% (36/221) vs 28.0% (53/189) , both P < 0.05)., Conclusions: 1, 3, 6, 9 and mixed infection are the main UU serotypes in female cervix.Serotype 3 and mixed infection may be associated with female genital infection.

Ureaplasma urealyticum (UU) is closely related to human diseases including non-gonococcal urethritis (NGU), infertility, premature membranes and neonatal bronchopulmonary dysplasia. Researches on the pathogenicity of UU have become a hot topic in recent years, and suggest that many potential pathogenicity genes or putative pathogenicity islands are involved in its virulence. Moreover, the biovar and serum types of UU, the infection concentration and the state of the host immune system are also important to determine whether UU can cause human disease or not. In this article the recent progress of researches in the pathogenicity of UU is reviewed.

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.

The aim of the research was to explore women with reproductive problems and pregnant women on Mycoplasma and Ureaplasma as well as to investigate spread of these microbes in the women of reproductive age. There were investigated 100 women with reproductive problem and 96 pregnant women. It was found that 64% of women with reproductive problem and 60% of pregnant women had Ureaplasma urealyticum with high titer (more then 1000 cells in ml), but Mycoplasma hominis was detected approximately in equal % of non-pregnant and pregnant women (12% - non-pregnant women; 16% - pregnant women). It is recommended to investigate women before planning pregnancy.

The aim of this study was to establish a murine model of lower genital tract infection by Ureaplasma urealyticum and Ureaplasma parvum and evaluate differences in pathogenicity of five serotypes. BALB/c female mice were divided into seven groups (five mice in each group), including five groups infected in the lower genital tract after treatment with estradiol with U. urealyticum serotypes 4 and 8 and U. parvum serotypes 1, 3, and 6, respectively, and two control groups of untreated mice and estradiol treated mice. The presence of infection was determined on solid and liquid culture media. Tumor necrosis factor-alpha (TNF-α) expression in lower genital tract secretions was determined by PCR, and morphological and histological changes of the lower genital tract were observed. The genital secretions of all inoculated mice were positive for U. urealyticum and U. parvum on culture in both liquid and solid media. TNF-α expression at 7 and 14 days after infection was markedly increased as compared with that of the controls. Morphological changes of the external genitalia included hair loss and erosions, and histological examination revealed infiltration by inflammatory cells. The five serotypes tested were all found to be pathogenic, and the pathogenicity varied with serotype 4 showing the greatest pathogenicity.

Problem: We compared the frequency of intra-amniotic infection in preterm labor (PL) with women not in labor, and correlated infection with amniotic fluid (AF) cytokines. Detailed identification of species, especially mycoplasmata, was tried to improve our understanding of the pathogenesis of PL., Method of Study: AF from 20 women with PL and 20 controls were evaluated. Infection was detected by PCR for Mycoplasma hominis, Ureaplasma urealyticum and 16S rRNA bacterial gene, which was cloned and sequenced for bacterial identification. Interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α levels were measured by ELISA., Results: Frequency of intra-amniotic infection is higher in PL (40.0%). Sequencing-based method identified Bacteroides fragilis, Prevotella bivia and Leptotrichia amnionii, in addition to Mycoplasma species detected by PCR. AF infection correlated with increased IL-1β and IL-6 levels., Conclusion: The frequency of intra-amniotic infection, especially M. hominis, in PL women who delivered with 7 days, is high and correlates with high IL-1β and IL-6 levels, but not IL-8., (© 2011 John Wiley & Sons A/S.)

Aim: To study the possibility of existence of antigenemia during urogenital mycoplasmal infections by detection the antigens of agents in blood and viscera of infected animals., Materials and Methods: Rabbits and mice were intraperitoneally inoculated with Mycoplasma hominis and Ureaplasma urealyticum, their antigens and DNAs. Samples of blood and visceral organs were studied by several methods: cultural with use of standard media, PCR, RT-PCR, indirect hemagglutination test, and immunofluorescence assay for detection of antibodies., Results: Bacteremia with M. hominis develops during 2 months after inoculation in rabbits and 3 weeks after inoculation in mice. Antigens of M. hominis and U. urealyticum were detected in serum and visceral organs significantly frequently than live cells and DNAs. Prolonged preservation of the antigens in animals' blood and viscera after intraperitoneal administration of "pure" antigens points to the presence of true mycoplasmal antigenemia. Forms of existence of antigens in organism are different-they can represent corpuscular antigens as well as soluble molecular compounds circulating in blood both in free state and in structure of immune complexes. Antigens as well as live cells are preserved in all studied organs., Conclusion: Inoculation of rabbits and mice with M. hominis or U. urealyticum resulted in development of generalized infection with persistence of the agent in all studied organs during initial phase of infection and predominant persistence in organs of immunogenesis during later phases.

Objective: To study the pathogenicity of Ureaplasma urealyticum serotype 3 (UU3) with different concentration in the genital tract of the mice., Methods: A total of 156 Kunming mice were divided into 4 groups randomly, including group A, B, C (48 mice in every experimental group) and control group (12 mice in control group). UU 3 at concentration of 1x10(7) copy/g (group A), 1x10(6) copy/g (group B), 1x10(5) copy/g (group C) were inoculated into 48 mice in every experimental group intravaginally, in the mean time, culture medium of UU was given into 12 mice in control group. They were necropsied at 1, 3, 7, 14, 21, 35 days of postinoculation randomly, which included 8 mice of every experimental group and 2 mice of control group every time, and to detect UU3 expression from cervical secretions by FQ-PCR and observing the pathogenicity rate in tissues of cervix, endometrium, fallopian tube by light microscope and calculate the morbidity rate., Results: (1) The total positive rates of UU3 were 63% (30/48) in group A, 50% (24/48) in group B, 17% (8/48) in group C, which showed a significant difference (P<0.01). And at 1, 3, 7, 14, 21, 35 days of postinoculation, the positive rates of group A were 8/8, 7/8, 6/8, 5/8, 4/8 and 0, group B were 7/8, 5/8, 5/8, 4/8, 3/8 and 0, group C were 3/8, 2/8, 2/8, 1/8, 0 and 0; all mice in control group were zero. At all time points, there were statistical difference in the positive rate among three experimental groups only at 1 day (P<0.05). (2) In the positive mice, their UU3 quantity concentration at 1, 3, 7, 14, 21 days were 1.70x10(7), 8.26x10(6), 4.04x10(6), 2.86x10(6), and 2.41x10(5) copy/g in group A; 3.75x10(6), 2.56x10(6), 1.37x10(6), 6.72x10(5), and 1.12x10(5) copy/g in group B, and 1.45x10(5), 1.07x10(5), 5.43x10(4), 4.68x10(3), and 0 copy/g in group C. There were statistical difference among experimental groups at all time points except 21 days (P<0.05). Comparing the concentration among all time points of every group, both group A and B showed a significant difference (P<0.05), group C didn't reach it (P>0.05). (3) The total pathogenicity rates of three groups were significant different at 7-35 days, which were 56% (18/32) in group A, 44% (14/32) in group B, 6% (2/32) in group C (P<0.01). And at 7, 14, 21, 35 days of postinoculation, the pathogenicity rates in group A were 5/8, 5/8, 4/8 and 4/8, group B were 4/8, 4/8, 3/8 and 3/8, group C were 1/8, 0, 1/8 and 0; all mice in control group were zero, which demonstrated significant difference only at 14 days (P<0.05), no other statistical difference were observed (P>0.05)., Conclusions: The pathogenicity of UU3 varies with different concentration in genital tract of mice. When UU3 concentration is more than 1x10(6) copy/g, the susceptibility to infection was intensified significantly.

Objective: To investigate the influence of culture proven intrauterine infection on preterm morbidity and to test the effect of antimicrobial treatment., Methods: Retrospective cohort study conducted between October 1997 and February 2001 in patients with preterm premature rupture of membranes or preterm labor. Vaginal swabs were sampled and amniocentesis for microbiologic culture of the amniotic fluid was performed. Patients with Ureaplasma urealyticum in the amniotic fluid were treated with josamycin. Infants were followed post partum according to birth weight, gestational age, APGAR score and infant morbidity., Results: In 49 eligible patients, 40% of cultures were positive, 22% for Ureaplasma urealyticum, 12% for other bacteria and 6% for candida. Children of mothers with positive amniotic fluid cultures had significantly lower gestational ages (26+4 weeks for Ureaplasma urealyticum [p=0.04] and 25+5 weeks for other microorganisms [p=0.0017] versus 28+6 weeks for mothers with negative amniotic fluid cultures) and lower birth weights (975 g [n.s.] and 828 g [p=0.0072] versus 1,041 g) but were appropriate for their gestational ages. 33.3% and 66.7% versus 24% of the children were mechanically ventilated [n.s.], duration of mechanical ventilation was 5.3 [p=0.02] and 10.1 days [p=0.04] versus 1.4 days, and prevalence of chronic lung disease was 38% and 33% versus 11% [n.s.]. Prevalence of severe intraventricular hemorrhage (12.5% [n.s.] and 33% [p=0.04] versus 3.4%) and nosocomial infections (50% for both groups of positive cultures versus 10.3% for negative cultures, p=0.02 and 0.03, respectively) was higher and median length of stay was significantly longer (121 [p=0.02] and 107 days [p=0.03] versus 60 days) in these patients. Maternal positive vaginal swab cultures were not associated with any of the above-mentioned factors. In none of the patients treated with macrolids for proven Ureaplasma urealyticum amnionitis could the microbes be eradicated., Conclusion: Maternal positive amniotic fluid cultures have been associated with lower gestational age and lower birth weight. Rate of infant morbidity was higher and length of stay was significantly longer in this group. Positive vaginal swabs were not predictive for infant morbidity. Treatment of mothers showing positive amniotic fluid cultures with macrolids was not effective.

Purpose of Review: Ureaplasma urealyticum is a frequent commensal in the lower genital tract of sexually active women. It may be transmitted perinatally from the colonized mother to her offspring, often resulting in prematurity and neonatal disease. The microorganism also sustains a causative role for infectious diseases in older children., Recent Findings: U. urealyticum infection can be diagnosed by culture, polymerase chain reaction, and the detection of specific antibodies. Neonatal infection has been implicated in various pathological conditions including pneumonia, chronic lung disease, central nervous system disorders, sepsis, osteomyelitis and even death. Older children may present with wheezing, pneumonitis, pertussis-like syndrome and different forms of arthritis. Large well-designed trials have demonstrated that the regular administration of antibiotics to vaginally colonized women are not beneficial in terms of preventing preterm labour. Macrolide-containing antibiotic regimens are, however, recommended for preterm premature rupture of the membranes. Erythromycin treatment of ureaplasma respiratory colonized premature infants shows no reduction in the incidence of chronic lung disease. Treatment of central nervous system infections, sepsis and arthritides includes tetracyclines, fluoroquinolones and anti-inflammatory agents, respectively., Summary: This review covers recent evidence concerning the role of U. urealyticum as a pathogen during childhood. It also includes an evaluation of contemporary diagnostic techniques and optimal therapeutic approaches.

The genital mycoplasmas represent a complex and unique group of microorganisms that have been associated with a wide array of infectious diseases in adults and infants. The lack of conclusive knowledge regarding the pathogenic potential of Mycoplasma and Ureaplasma spp. in many conditions is due to a general unfamiliarity of physicians and microbiology laboratories with their fastidious growth requirements, leading to difficulty in their detection; their high prevalence in healthy persons; the poor design of research studies attempting to base association with disease on the mere presence of the organisms in the lower urogenital tract; the failure to consider multifactorial aspects of diseases; and considering these genital mycoplasmas only as a last resort. The situation is now changing because of a greater appreciation of the genital mycoplasmas as perinatal pathogens and improvements in laboratory detection, particularly with regard to the development of powerful molecular nucleic acid amplification tests. This review summarizes the epidemiology of genital mycoplasmas as causes of neonatal infections and premature birth; evidence linking ureaplasmas with bronchopulmonary dysplasia; recent changes in the taxonomy of the genus Ureaplasma; the neonatal host response to mycoplasma and ureaplasma infections; advances in laboratory detection, including molecular methods; and therapeutic considerations for treatment of systemic diseases.

Ureaplasma urealyticum and Mycoplasma hominis colonized 20-40% of newborns and are more frequent in premature. They are responsible for localized infections such as pleural effusion, pneumopathy, adenopathy, abscess or systemic sepsis. An important hyperleukocytosis is often associated with pulmonary infections. Their responsibility, as pathogen agents, is questionable in some non bacterial meningitis. There is large controversy for their role as cofactor, in chronic lung disease (bronchopulmonary dysplasia) and periventricular leukomalacia, because of a too low number of newborns in prospective trials. Genital mycoplamas are resistant to beta lactamines. Macrolides have a good sensitivity, particularly josamycine, but Mycoplasma hominis is resistant to erythromycin. For systemic sepsis, fluoroquinolones such as ciprofloxacine have less deleterious effects than IV erythromycin.

Ureaplasma urealyticum genital tract colonization of pregnant women has been associated with an adverse pregnancy outcome, while its consequent perinatal transmission has been implicated in the development of respiratory disease of the neonate. Clinical manifestations or contributions of ureaplasmal airway colonization in newborns mainly include pneumonia, precocious dysplastic changes and chronic lung disease; although systemic disease has also been documented. This review aims to summarize current diagnostic techniques, pathogenetic mechanisms and pathological data in an attempt to establish an optimal therapeutic approach regarding neonatal U. urealyticum respiratory infection. Related morbidity and mortality, along with the high economic impact of neonatal respiratory disease worldwide, renders this topic particularly interesting and promotes further research in this field.

Ureaplasma urealyticum respiratory tract colonization in preterm infants has been associated with a high incidence of pneumonia and the development of bronchopulmonary dysplasia. However, study of this human pathogen has been hampered by the absence of animal models. We have developed the first juvenile mouse model of Ureaplasma pneumonia and characterized the histopathology during the month following inoculation. C3H/HeN mice were inoculated intratracheally with a mouse-adapted clinical Ureaplasma isolate (biovar 2) or sham inoculated with 10B broth. Culture of lung homogenates and PCR of DNA from bronchoalveolar lavage fluid (BAL) confirmed the presence of Ureaplasma in 100% of inoculated animals at 1 day, 60% at 2 days, 50% at 3 days, and 25% at 7 and 14 days. Ureaplasma was undetectable 28 days postinoculation. There were marked changes in BAL and interstitial-cell composition with increased number of polymorphonuclear leukocytes 1 to 2 days and 14 days postinoculation and macrophages at 2 and 14 days postinoculation. The Ureaplasma infection caused a persistent focal loss of airway ciliated epithelium and a mild increase in interstitial cellularity. There were no differences in BAL protein concentration during the first 28 days, suggesting that pulmonary vascular endothelial barrier integrity remained intact. Comparison of BAL cytokine and chemokine concentrations revealed low levels of tumor necrosis factor alpha (TNF-alpha) at 3 days and monocyte chemoattractant protein 1 at 7 days in Ureaplasma-infected mice but a trend toward increased TNF-alpha at 14 days and increased granulocyte-macrophage colony-stimulating factor and interleukin-10 at 28 days. These data suggest that Ureaplasma alone may cause limited inflammation and minimal tissue injury in the early phase of infection but may promote a mild chronic inflammatory response in the later phase of infection (days 14 to 28), similar to the process that occurs in human newborns.

Three serovars (5, 8 and 10) of Ureaplasma urealyticum were inoculated intravaginally into groups of oestradiol-treated young adult BALB/c strain mice. Hormone treatment was essential for vaginal colonisation. The proportion of mice colonised initially and the persistence of colonisation were different with the three serovars; half of those given serovar 8 were still colonised after 84 days. A strain of serovar 5 after a further 50 subcultures in vitro was a little less persistent than it was before such subculture, but not in a way to suggest that subculturing was the main reason for differences in the behaviour of the serovars. At autopsy of six mice that were still colonised vaginally 158 days after inoculation of serovar 8, spread to the upper genital tract was shown to have occurred in three of them and dissemination to the liver and kidney in one. Compared with immunocompetent mice of strain CB20, such dissemination was not a feature in genetically related mice with severe combined immunodeficiency. This is not in keeping with the situation in hypogammaglobulinaemic patients in whom ureaplasmas and other mycoplasmas are known to disseminate. However, differences in the proportion of immunocompetent mice colonised or in ureaplasmal persistence with different serovars may act as a marker for differences in human pathogenicity and is worthy of further study.

Background: Chronic inflammatory processes contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized colonisation with Ureaplasma urealyticum (Uu) as a possible reason for an increased risk of developing prolonged oxygen dependency > 28 days in very low birth weight (VLBW) infants., Patients and Methods: From January 1998 to November 1999 pharyngeal swabs were prospectively obtained and tested for Uu at birth and then weekly in VLBW infants. The following variables were compared between Uu-positive and Uu-negative infants: prenatal corticosteroids, maternal infections, mode of delivery, gestational age, birth weight, gender distribution, RDS, surfactant therapy, maximum inspiratory oxygen concentration during the first 24 and 48 hours, duration of oxygen supplementation beyond day 28, PDA, and weight differences during the first week of life., Results: Of a total of 74 infants, 17 were found to be Uu-positive. The latter group showed a lower mean gestational age (29; 25 - 37 vs. 28; 24 - 34 WOG; p = 0.02) and a longer duration of oxygen supplementation after day 28 (0; 0 - 121 vs. 5; 0 - 134 d; p = 0.02). All other variables did not differ significantly between both groups. Multivariate analyses identified the variables birth weight and colonisation with Uu as risk factors for a longer period of oxygen dependency after day 28 (p < 0.01; p = 0.05)., Conclusion: These data indicate a correlation between the colonisation with Uu and prolonged oxygen dependency > 28 days.

Chronic lung disease (CLD) of prematurity remains a significant cause of morbidity among premature infants. It is a multifactorial disorder and characterized by an early increased number of neutrophils and alveolar macrophages, with later architectural epithelial and endothelial cell damage. Recently, apoptosis of type 2 pneumocytes in the lung of preterm neonates with acute and chronic lung disease has been examined and apoptosis of mesenchymal cells was detected in the chronic stage of bronchopulmonary dysplasia. Infection and inflammatory responses in the lungs play important roles. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated. We found that U. urealyticum induced apoptosis in human type II lung epithelial cells (A549 cell line) and macrophages (derived from human monocytic cell line THP-1) by measuring the outer leaflets translocation of phosphatidylserine (flow cytometry analysis and fluorescence microscopy assessment), DNA fragmentation analysis, cell morphology changes such as diminution in cell volume, increased cytoplasmic staining, and nuclear pyknosis (hematoxylin and eosin staining) and viable counting (trypan blue exclusion). Anti-TNF-alpha monoclonal antibody partially protected the macrophages from undergoing apoptosis after infection with U. urealyticum. Our findings imply that U. urealyticum might be involved in impairing lung structure and host immune response during the development of CLD., (Copyright 2002 S. Karger AG, Basel)

Background: An exaggerated inflammatory response occurs in infants who subsequently develop bronchopulmonary dysplasia (BPD). Ureaplasma urealyticum (Uu) is frequently isolated from cultures of tracheal secretions obtained from very low birth weight infants and is associated with an increased risk of BPD., Methods: We examined the relationships between isolation of genital mycoplasmas, tracheal aspirate (TA) interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) concentrations and the development of BPD. Serial TAs were obtained prospectively from 35 very low birth weight infants, and IL-8 and MCP-1 concentrations were determined by enzyme-linked immunoadsorbent assay. Tracheal cultures for bacteria and genital mycoplasmas were performed on aspirates obtained during the first 2 days of life., Results: Infants who developed BPD (n=18) were less mature (25.2+/-0.2 vs 27.8+/-0.5 weeks; P<0.001), of lower birth weight (746+/-28 vs 1052+/-41 g; P<0.001), and more likely to have a positive tracheal culture for Uu (39% vs 6%; P=0.026) than those who did not develop BPD (n=17). Tracheal concentrations of IL-8 and MCP-1 were significantly increased in infants who developed BPD (IL-8: P=0.0001; MCP-1: P<0.001, analysis of variance) and correlated with duration of mechanical ventilation and oxygen treatment. Uu-positive infants had an increased incidence of BPD (88% in infants with Uu vs 42% in infants without Uu; P=0.020) and had TA concentrations of IL-8 and MCP-1 that were significantly increased compared with those of Uu-negative infants., Conclusions: Increased TA concentrations of IL-8 and MCP-1 during the first 2 weeks of life are associated with the development of BPD. Recovery of Uu from TAs is associated with a more robust inflammatory reaction and an increased risk of BPD.

Background: The aim of this case control study was to investigate the influence of genital Ureaplasma urealyticum colonization on pregnancy outcome., Methods: One hundred and seventy-two women colonized with Ureaplasma urealyticum without co-existing other infections and 123 women with negative cultures for Ureaplasma urealyticum were enrolled. In a multivariate analysis the influence of quantitative Ureaplasma urealyticum colonization level was determined., Results: Compared to the negative women increasing colonization with Ureaplasma urealyticum was associated with a significant decrease of birth weight (p<0.0001) and gestational age (p<0.0001) and with a significant increase of chorioamnionitis (p<0.0001) and preterm delivery (p<0.001). In a multivariate analysis high-density Ureaplasma urealyticum colonization was an independent risk factor for chorioamnionitis and preterm delivery, whereas low colonization levels had no effect on an adverse outcome of pregnancy., Conclusions: The degree of colonization with Ureaplasma urealyticum correlates strongly with an adverse effect on pregnancy outcome.

The comparison of the genomes of two very closely related human mucosal pathogens, Mycoplasma genitalium and Mycoplasma pneumoniae, has helped define the essential functions of a self-replicating minimal cell, as well as what constitutes a mycoplasma. Here we report the complete sequence of a more distant phylogenetic relative of those bacteria, Ureaplasma urealyticum (parvum biovar), which is also a mucosal pathogen of humans. It is the third mycoplasma to be sequenced, and has the smallest sequenced prokaryotic genome except for M. genitalium. Although the U. urealyticum genome is similar to the two sequenced mycoplasma genomes, features make this organism unique among mycoplasmas and all bacteria. Almost all ATP synthesis is the result of urea hydrolysis, which generates an energy-producing electrochemical gradient. Some highly conserved eubacterial enzymes appear not to be encoded by U. urealyticum, including the cell-division protein FtsZ, chaperonins GroES and GroEL, and ribonucleoside-diphosphate reductase. U. urealyticum has six closely related iron transporters, which apparently arose through gene duplication, suggesting that it has a kind of respiration system not present in other small genome bacteria The genome is only 25.5% G+C in nucleotide content, and the G+C content of individual genes may predict how essential those genes are to ureaplasma survival.

Ureaplasma urealyticum is relatively common in the respiratory tract of very low birth weight infants and has been hypothesized to be involved in the development of chronic lung disease. The purpose of this study was to investigate whether U. urealyticum could stimulate macrophages to produce proinflammatory cytokines in vitro, which are early pathologic changes in the lung during the development of chronic lung disease. A human monocytic cell line (THP-1) differentiated to macrophages, a rat alveolar macrophage cell line (Nr8383), and human lung macrophages from tracheobronchial aspirate fluid in preterm infants were exposed to U. urealyticum antigen for 24 h. The protein levels of human IL-6, tumor necrosis factor-alpha (TNF-alpha), and rat TNF-alpha were measured with ELISA. Rat IL-6 was analyzed with a specific bioassay. The mRNA levels of these cytokines were detected by reverse transcriptase-PCR. The production of TNF-alpha and IL-6 increased after stimulation with U. urealyticum in both the human and rat macrophage cell lines. In tracheobronchial aspirate fluid macrophages, U. urealyticum increased the production of TNF-alpha from 14 to 84% and IL-6 from 46 to 268% above control levels. U. urealyticum also induced gene expression of TNF-alpha and IL-6. In conclusion, U. urealyticum could be an important factor in the development of chronic lung disease because of its ability to induce alveolar macrophage proinflammatory cytokine production.

We trace the evidence-based evolution of ureaplasmal male infertility as an established clinical entity. We review epidemiology data, possible pathogenic mechanisms of Ureaplasma urealyticum in infertility, and the results of isolation studies and therapeutic trials. Future developments are outlined.

The presence of Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis was explored in 50 public restroom toilet bowls. We used culture, antigen detection, polymerase chain reaction, and survival assay. Five bowls (10%) were contaminated with at least one organism. U. urealyticum was found in four bowls, M. hominis in three, and C. trachomatis in one. U. urealyticum survived on the toilet rim for up to 2 hours.

The in-vitro effects of several concentrations of Ureaplasma urealyticum on the motility, membrane integrity and morphology of washed spermatozoa from healthy donors were studied. A significant reduction in sperm motility and signs of membrane alteration, directly related to U.urealyticum concentration and contact time were observed. Scanning electron microscopy examination showed masses of U. urealyticum attached to the head and middle piece of some of deformed spermatozoa. It is suggested that U.urealyticum is involved in sperm changes leading to male infertility, particularly when there is heavy U. urealyticum colonization or specific infections with this microorganism.

A cohort of 78 infants of gestational age less than 34 weeks was examined for Ureaplasma urealyticum colonization and neonatal morbidity. Ureaplasma urealyticum was cultured from nasopharyngeal, endotracheal and blood-culture samples. A child was considered as being colonized if any sample was positive. The children with perinatal U. urealyticum colonization (n = 11; 14%) differed from those with no colonization (n = 67) in two important aspects: (i) they had higher leucocyte counts on the first (18.6 vs 12.4 10(9)) and the second (29.0 vs 15.4 10(9)) days of life (p = 0.01, both days); and (ii) they more often needed high-frequency oscillatory ventilation (45% vs 13%, p = 0.02). This study showed that U. urealyticum colonization is associated with signs of the host defence response together with symptoms of respiratory tract involvement suggesting the pathogenicity of U. urealyticum in premature infants.

The possibility that Ureaplasma urealyticum might play an important role in human infertility was first raised more than 20 years ago, but this association remains speculative. Considering the hypothesis that the pathogenicity of Ureaplasma urealyticum may depend on its serotypes, the clastogenic effects of different strains of Ureaplasma urealyticum, at concentrations of 10(3) CCU (color changing units)/ml, 10(4) CCU/ml and 10(5) CCU/ml, were evaluated in vitro in short-term cultures of human lymphocytes. Total or partial mitotic inhibition was produced by Ureaplasma urealyticum serotypes 2, 3 and 10 independent of the concentration (10(3) CCU/ml, 10(4) CCU/ml or 10(5) CCU/ml) of the microorganisms employed. In contrast, the clastogenic effects observed with serotypes 1, 7 and 12 varied according to the concentration employed in the test. Mitotic alterations were observed in Ureaplasma urealyticum serotypes 5, 6, 7, 8, 9, 11 and 12. Chromatid gaps (53.0%) and chromatid breaks (13.9%) were the most frequent types of alterations observed. The results of this in vitro assay demonstrated that the clastogenic effects varied with the Ureaplasma urealyticum serotypes evaluated.

This study was undertaken to test the effects of erythromycin as an adjunct to tocolysis for preterm labor in women with vaginal cultures positive for Ureaplasma urealyticum. The study group consisted of 18 women in active preterm labor with pregnancies between 26 and 34 weeks of gestation and intact membranes who received 500 mg erythromycin orally every 8 h for 10 days. Seventeen women with similar characteristics served as controls and received no antibiotics. In all women contractions were suppressed with ritodrine. Erythromycin treatment resulted in a statistically significant greater mean delay of delivery (36.4 days) than among the control group (23.1 days). Higher proportion of term pregnancies (7 versus 3 pregnancies), higher mean birth weight (2,745 versus 2,474 g), lower neonatal morbidity (22.2 versus 42.2%) and shorter mean neonatal hospitalization time (9.6 versus 12.1 days) were observed, although these differences were not statistically significant. Adjunctive erythromycin treatment given to women treated for preterm labor with intact membranes and positive vaginal cultures for U. urealyticum appears to prolong gestation and to improve perinatal outcome.

Ureaplasma urealyticum is a fastidious organism which is not recovered by conventional bacterial cultures techniques, but special cultures are required for its isolation and identification. As it is a urease-producing organism, it is considered a risk factor for the formation of struvite calculi in the urinary tract. A total of 30 patients with urinary infection stones (19 of them with the 1st formation and 11 with recurrent stone formation) were included in the study. Both bladder urine specimen (cystoscopically obtained) and stones removed were subjected to conventional cultures and also to Ureaplasma specific cultures (A7 agar and U9 broth). The results of culture techniques revealed that 86.7% of patients had aerobic organisms (E. coli in 46.7%, Klebsiella in 30%, Proteus in 6.7% and Pseudomonas in 3.3%) and 26.7% showed U. urealyticum in mid stream urine. As regards stone cultures, they revealed aerobic organisms in 76.7%, and U. urealyticum in 20%. Sensitivity tests for U. urealyticum showed that minocycline was the most effective antimicrobial followed by tetracycline and ciprofloxacin. From these data, we conclude that U. urealyticum may be the causative organism for infection stone and should be searched for via its specific cultures, especially in patients with recurrent stones and with the so-called sterile pyuria.

Fourteen serotypes are currently recognized in the Ureaplasma urealyticum species. These serotypes have been divided into two genomic clusters or biovars by a large number of typing methods. The parvo-biovar includes strains of serotypes 1, 3, 6 and 14 and the T960-biovar, strains belonging to the ten other serotypes. In this study, arbitrarily primed polymerase chain reaction (AP-PCR) has been applied to the analysis of reference strains of the 14 U. urealyticum serotypes. By using two different sets of 10-mer oligonucleotide primers, the method allowed the clear differentiation between the two known biovars of the species. However, further differentiation within a same biovar was only achieved for a few standard strains of the T960-biovar analysed by using a pairwise combination of primers. The reproducibility of AP-PCR profiles was shown on strains tested after repeated subcultures and with different thermal cyclers. Additional experiments were performed on forty isolates of U. urealyticum recovered from subjects of various origins. They confirmed that AP-PCR was able to identify the strains at the biovar level. With reference to the other typing methods, AP-PCR is easy to perform and can be applied to large numbers of strains for epidemiological purposes.

Vaginal cultures for Ureaplasma urealyticum and confidential questionnaires were obtained from women with signs and symptoms of vaginitis who consulted a physician at a Primary Health Center, Tlalpan, D.F., México. In all 220 women were studied, 50 (22.7%) of whom were colonized with Ureaplasma urealyticum, statistical analysis (X2) showed there was no association between colonization with Ureaplasma urealyticum, and age, pregnancy, and other but there was association between colonization with Ureaplasma urealyticum and the number of pregnancies and no birth control method use.

Mycoplasma hominis was isolated in pure culture from septic synovial aspirates from an individual (patient A) during 16 different bouts of exacerbation over a 70-month period of observation. Two isolates, 10(7) and also 10(6) color-changing units (CCU) of the 1620 isolate and 5 x 10(4) CCU of the 1628 isolate, caused inflammation in chimpanzees inoculated intraarticularly. Inflammation was also induced with 10(7) CCU of the 2010B isolate, serovar VII of Ureaplasma urealyticum, recovered from an agammaglobulinemic individual (patient B) with septic polyarthritis and with 3 x 10(6) CCU of the PI-1428 isolate of Mycoplasma pneumoniae. Inflammation persisted for up to 36 days and was self-limiting. The aspirates contained up to 220,000 white blood cells/mm3 and up to 10(7) CCU/mL. There was good correlation between the severity of inflammation and the numbers of organisms, but antibody was not detected in aspirates during the peak severity of disease. As the numbers of organisms, decreased, detectable levels of antibody increased, thus suggesting that antibody may have been bound to antigen. Chimpanzees previously infected with either the 1628 isolate of M. hominis or the 2010B isolate of U. urealyticum were protected on challenge with > 100 times the minimal dose causing arthritis. Chimpanzees showed little or no inflammation when inoculated intraarticularly with 5 x 10(8) CCU of the type strain PG-21 of M. hominis or with the type strain CO of U. urealyticum or when inoculated intravenously with 3 x 10(8) CCU of the arthrogenic 1620 isolate of M. hominis.

On the ground of contemporary medical literature and our own observations, we have tried to estimate the participation of microorganism infection in preterm labor. In this article, we present mechanism, currently recognized as the most probable, that are leading to preterm labor under condition of perinatal infections. One of them seems to be the production of enzymes by pathological strains. Those enzymes are considered to stimulate decidual and amniotic cells to arachidonic acid metabolism and prostaglandins synthesis. Coexisted with chorionamnionitis the migration of leukocytes that are able to induce prostaglandins synthesis releasing interleukin, can also be an important factor of preterm labor.

Cultures positive for Ureaplasma urealyticum in babies weighing < 1000 g have been associated with both chronic lung disease (CLD) and death, but no definite causality has been established. To further investigate the role of the organism in CLD, we colonized premature baboons with U. urealyticum and compared resulting pathology with that in uninoculated control animals. Using an established model of prematurity, the 140-day-gestation baboon, three animals were colonized with U. urealyticum via endotracheal tube. All had hyaline membrane disease, indistinguishable from disease in human infants, and U. urealyticum infection. Samples obtained from nasopharynx, trachea, pleural fluid, and, at necropsy, lung tissue produced positive cultures. Culture of blood from one animal yielded U. urealyticum. On pathologic examination, after 6 days of ventilation, all three of the infected animals had the specific pathologic finding of bronchiolitis with epithelial ulceration not seen in four uninfected control animals. Thus, U. urealyticum is capable of causing a pathologically recognizable pulmonary lesion in premature primates with hyaline membrane disease.

Recent studies show an association between the presence of Ureaplasma urealyticum in tracheal aspirates and bronchopulmonary dysplasia. We hypothesized that among infants with birth weights < or = 1,250 g and respiratory disease, those with U. urealyticum in their tracheal aspirates would have radiographic evidence of more-severe pulmonary disease more often than would those without this organism. A total of 292 low-birth-weight infants who had endotracheal aspirate cultured within 7 days of birth were enrolled. The radiographic outcome variables were pneumonia, early severe bronchopulmonary dysplasia (precocious), and chronic lung disease. Microorganisms were isolated from 128 infants (44%); U. urealyticum was isolated from 44 (15%). Pneumonia was significantly more common in infants with than without U. urealyticum (30% vs. 16%, P = .03). U. urealyticum also was associated with precocious bronchopulmonary dysplasia independent of prematurity, race, and sex (odds ratio, 2.2; P < .05). Tracheal isolation of U. urealyticum within 7 days of birth is associated with pneumonia and precocious bronchopulmonary dysplasia.

This study examined the association between Ureaplasma urealyticum colonization and the development of chronic lung disease (CLD) in 93 premature infants who were treated with surfactant and who had birth weights < 1251 g. Nasopharyngeal and tracheal cultures for U. urealyticum were obtained at 2 +/- 1 and at 14 +/- 1 days after birth and were positive in 17 (18%) of 93 patients. Infants born vaginally were 4.5 times more likely to be colonized than were those born by cesarean section. Colonization with U. urealyticum was associated with 1.66 (95% confidence interval, 1.24-2.20, P = .024) times the risk of developing CLD and with a greater incidence of > or = 2+ polymorphonuclear leukocytes in the tracheal aspirate at 2 +/- 1 days of age compared with uncolonized infants (P = .025). We conclude that U. urealyticum colonization is associated with CLD even after surfactant treatment. The presence of U. urealyticum is also associated with inflammatory cells in the tracheal aspirate.

Evidence related to the association of Ureaplasma urealyticum with premature birth is reviewed. U. urealyticum is a common inhabitant in the vagina of pregnant women. It is recovered from the vaginas of approximately 70% of pregnant women. The presence of U. urealyticum in the vagina is not associated with premature birth. Therapy to eradicate U. urealyticum from the vagina during pregnancy does not reduce the incidence of premature birth. Recovery of U. urealyticum from the amniotic fluid has not been associated with prematurity. However, in three of six reports, the recovery of U. urealyticum from the chorioamnion has been associated with prematurity, and U. urealyticum is rather consistently associated with histological chorioamnionitis. This review suggests that U. urealyticum in the lower genital tract is not associated with premature birth but that its presence in the chorioamnion is weakly associated with prematurity and strongly associated with histological chorioamnionitis.

Multiple insults may induce bronchopulmonary dysplasia (BPD) in premature infants, including the recently reported association of BPD with neonatal Ureaplasma urealyticum colonization. One mechanism of damage could involve stimulation of proinflammatory cytokine release from pulmonary fibroblasts. We therefore compared the effects of U. urealyticum, oxygen, and lipopolysaccharide (LPS) on the release of interleukin (IL)-1 beta, IL-6, and IL-8 from neonatal fibroblasts. Fibroblasts were grown in multiwell plates and divided into the following experimental conditions: fibroblasts alone, fibroblasts plus U. urealyticum (10,000 cfu/mL), and fibroblasts plus LPS (2 micrograms/mL). Plates were then exposed to room air or hyperoxia for 48 h, and supernatants were assayed for IL. U. urealyticum-infected fibroblasts produced a significant increase in IL-6 (P < .05) and a dramatic increase in IL-8 (P < .05) that was independent of hyperoxic exposure and significantly increased over that produced by LPS or hyperoxia alone. U. urealyticum is a potent inducer of fibroblast cytokine release in vitro and may contribute to the development of BPD.

A critical appraisal of four cohort studies examining the relationship between Ureaplasma urealyticum and chronic lung disease (CLD) of prematurity is presented. Three studies were concurrently conducted, but the fourth was conducted 4 years later when surfactant replacement was a widespread practice. Although infants were enrolled in all studies soon after birth before they had developed CLD, there were differences in patients population, the definition of colonization with U. urealyticum, neonatal management, and the definition of CLD of prematurity. Despite the differences, all four studies found an association between colonization and development of CLD of prematurity. A combined estimate of relative risk for the four studies was 1.91 (95% confidence interval, 1.54-2.37). When infants were categorized into groups by birth weight, the association was not observed in infants who weighed > 1,250 g. The association was also not observed in infants who weighed < 750 g, but the risk of CLD of prematurity in the uncolonized control group was already 82%. Because the cohort study design allows for the possibility that one or more additional factors associated with U. urealyticum may be the true cause(s) of CLD of prematurity, there is strong but not definitive evidence that U. urealyticum causes CLD of prematurity.

We present a case of premature twins, born at 24 weeks of gestation. Both infants died of intraventricular hemorrhage, aged 1 and 3 days, respectively. Ureaplasma urealyticum was isolated from brain tissue obtained at the autopsy of both infants. Our observations lend additional evidence of the role of U. urealyticum as a central nervous system pathogen in premature infants.