Ureaplasma parvum meningitis following atypical choroid plexus papilloma resection in an adult patient: a case report and literature review

Background While Ureaplasma parvum has previously been linked to the incidence of chorioamnionitis, abortion, premature birth, and perinatal complications, there have only been rare reports of invasive infections of the central nervous system (CNS) in adults. Owing to its atypical presentation and the fact that it will yield sterile cultures using conventional techniques, diagnosing U. parvum meningitis can be challenging. Case presentation We describe a case of U. parvum meningitis detected in an adult patient following surgical brain tumor ablation. After operation, the patient experienced epilepsy, meningeal irritation, and fever with unconsciousness. Cerebrospinal fluid (CSF) analysis showed leukocytosis (484 * 106 /L), elevated protein levels (1.92 g/L), and decreased glucose concentrations (0.02 mmol/L). Evidence suggested that the patient was suffering from bacterial meningitis. However, no bacterial pathogens in either CSF or blood were detected by routine culture or serology. The symptoms did not improve with empirical antibiotics. Therefore, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the meningitis. Ureaplasma parvum was detected by mNGS in CSF samples. To the best of our knowledge, this case is the first reported instance of U. parvum meningitis in an adult patient in Asian. After diagnosis, the patient underwent successful moxifloxacin treatment and recovered without complications. Conclusions As mNGS strategies can enable the simultaneous detection of a diverse array of microbes in a single analysis, they may represent a valuable means of diagnosing the pathogens responsible for CNS infections and other clinical conditions with atypical presentations.

Determination of In Vitro Antimicrobial Susceptibility for Lefamulin (Pleuromutilin) for Ureaplasma Spp. and Mycoplasma hominis

Lefamulin is the first of the pleuromutilin class of antimicrobials to be available for therapeutic use in humans. Minimum inhibitory concentrations of lefamulin were determined by microbroth dilution for 90 characterised clinical isolates (25 Ureaplasma parvum, 25 Ureaplasma urealyticum, and 40 Mycoplasma hominis). All Mycoplasma hominis isolates possessed lefamulin MICs of ≤0.25 mg/L after 48 h (MIC50/90 of 0.06/0.12 mg/L), despite an inherent resistance to macrolides; while Ureaplasma isolates had MICs of ≤2 mg/L after 24 h (MIC50/90 of 0.25/1 mg/L), despite inherent resistance to clindamycin. Two U. urealyticum isolates with additional A2058G mutations of 23S rRNA, and one U. parvum isolate with a R66Q67 deletion (all of which had a combined resistance to macrolides and clindamycin) only showed a 2-fold increase in lefamulin MIC (1–2 mg/L) relative to macrolide-susceptible strains. Lefamulin could be an effective alternative antimicrobial for treating Ureaplasma spp. and Mycoplasma hominis infections irrespective of intrinsic or acquired resistance to macrolides, lincosamides, and ketolides. Based on this potent in vitro activity and the known good, rapid, and homogenous tissue penetration of female and male urogenital tissues and glands, further exploration of clinical efficacy of lefamulin for the treatment of Mycoplasma and Ureaplasma urogenital infections is warranted.

Inflammatory Response Elicited by Ureaplasma parvum colonization in human cervical epithelial, stromal, and immune cells

Ureaplasma parvum is a commensal bacterium in the female reproductive tract but has been associated with pregnancy complications such as preterm prelabor rupture of membranes and preterm birth (PTB). However, the pathologic effects of U. parvum in the cervix, that prevents ascending infections during pregnancy, are still poorly understood. To determine the impact of U. parvum on the cervix, ectocervical (ecto) and endocervical (endo) epithelial and stromal cells were incubated with U. parvum. Macrophages were also tested as a proxy for cervical macrophages to determine the antigenicity of U. parvum. The effects of U. parvum, including influence on cell cycle and cell death, antimicrobial peptide production, epithelial-to-mesenchymal transition (EMT), and inflammatory cytokine levels, were assessed. U. parvum colonized cervical epithelial and stromal cells 4 hours post-infection. Like uninfected control, U. parvum neither inhibited cell cycle progression and nor caused cell death in cervical epithelial and stromal cells. U. parvum increased the production of the antimicrobial peptides (AMPs) cathelicidin and human β-defensin 3 and exhibited weak signs of EMT evidenced by decreased cytokeratin 18 and increased vimentin expression in cervical epithelial cells. U. parvum induced a pro-inflammatory environment (cytokines) and increased MMP-9 in cervical epithelial cells but promoted pro- and anti-inflammatory responses in cervical stromal cells and macrophages. U. parvum may colonize the cervical epithelial layer, but induction of AMPs and anti-inflammatory response may protect the cervix and may prevent ascending infections that can cause PTB. These findings suggest that U. parvum is a weak inducer of inflammation in the cervix.

Dual Ureaplasma parvum arthritis: a case report of U. parvum septic arthritis following contralateral reactive arthritis in an immunosuppressed patient

Background Ureaplasma parvum is usually part of the normal genital flora. Rarely can it cause invasive infections such as genitourinary infections, septic arthritis, or meningitis. Case presentation Here we present the first description of chronic ureterocystitis in a 56-year-old immunocompromised patient, complicated first by reactive arthritis and secondarily by contralateral septic arthritis due to U. parvum infection. U. parvum was detected in synovial fluid and in a urine sample. Treatment consisted of double-J stenting and targeted antibiotic therapy. Evolution showed resolution of urinary symptoms and clinical improvement of arthritis despite functional sequelae. Conclusions Given the high prevalence of U. parvum colonisation, this diagnosis should remain a diagnosis of exclusion. However, because of the difficulty in detecting this microorganism, it should be considered in unexplained subacute urethritis or arthritis, including reactive arthritis, especially in immunosuppressed patients. Real-time PCR positivity in the absence of a differential diagnosis should not be overlooked.

Phenotypic Antimicrobial Susceptibility and Genotypic Characterization of Clinical Ureaplasma Isolates Circulating in Shanghai, China

There is a growing global concern regarding the rise of antimicrobial resistance among Ureaplasma spp. isolates. However, studies on the antimicrobial susceptibility profiles, resistance mechanisms, and clonality of Ureaplasma spp. clinical isolates are still limited and cover only some geographic regions. Firstly, Ureaplasma species from the urogenital tracts of patients in Shanghai, China, were isolated by using the culture medium (A8 and 10B broth), and identified the genotype by polymerase chain reaction (PCR). Secondly, the antimicrobial susceptibility tests were determined by using broth microdilution assay. Then, the resistance genetic determinants to fluoroquinolones (FQs), macrolides, and tetracyclines were investigated through PCR/DNA sequencing. Finally, the molecular epidemiology of Ureaplasma species was studied by multilocus sequence typing (MLST). Among 258 isolates, Ureaplasma parvum (UPA) and Ureaplasma urealyticum (UUR) were found in 226 (87.60%) and 32 (12.40%) isolates, respectively. The minimum inhibitory concentrations (MICs) of 258 Ureaplasma spp. strains ranged from 0.015 to 64μg/ml for all 11 kinds of antimicrobials. Regardless of species, the isolates were most sensitive to AZI (1.94%), JOS (3.49%), and CLA (4.23%). Among them, there were 39 (15.12%) multidrug-resistant (MDR) strains, including 32 UPA isolates. The resistance rates of UPA to CIP (91.59%), and ROX (36.28%) were significantly higher than those of UUR. Twenty six FQ-resistant isolates had amino acid substitutions in gyrA and in parC (Ser83Leu). Mutations were detected in genes encoding ribosomal proteins L4 (Thr84Ile) and L22 (Ser81Pro) in macrolide-resistant isolates. Tet(M) was found in four UPA isolates. These mutations were mainly found in UPA isolates. Sequence type 1 (ST1) was the predominant ST, which contained 18 isolates. In conclusion, this study showed a higher resistance rate (especially to ROX and CIP), higher substitution rate, and higher MDR rate among UPA strains. The most active antimicrobial agents were AZI, JOS, and CLA. Identifying UPA or UUR in clinical isolates could help clinicians to choose appropriate drugs for treatment. The main resistance mechanisms may involve gene substitution of Ser83Leu in parC and Ser81Pro in L22. ST1 was the predominant ST of Ureaplasma isolates with MDR to FQs and macrolides in Shanghai, China.

Detection of Volatile Organic Compounds as Potential Novel Biomarkers for Chorioamnionitis – Proof of Experimental Models

Background: Histologic chorioamnionitis is only diagnosed postnatally which prevents interventions. We hypothesized that volatile organic compounds (VOCs) in the amniotic fluid might be useful biomarkers for chorioamnionitis and that VOC profiles differ between amnionitis of different origins.Methods: Time-mated ewes received intra-amniotic injections of media or saline (controls), or live Ureaplasma parvum serovar 3 (Up) 14, 7 or 3d prior to c-section at day 124 gestational age (GA). 100 μg recombinant ovine IL-1α was instilled at 7, 3 or 1d prior to delivery. Headspace VOC profiles were measured from amniotic fluids at birth using ion mobility spectrometer coupled with multi-capillary columns.Results: 127 VOC peaks were identified. 27 VOCs differed between samples from controls and Up- or IL-1α induced amnionitis. The best discrimination between amnionitis by Up vs. IL-1α was reached by 2-methylpentane, with a sensitivity/specificity of 96/95% and a positive predictive value/negative predictive values of 96 and 95%. The concentration of 2-methylpentane in VOCs peaked 7d after intra-amniotic instillation of Up.Discussion: We established a novel method to study headspace VOC profiles of amniotic fluids. VOC profiles may be a useful tool to detect and to assess the duration of amnionitis induced by Up. 2-methylpentane was previously described in the exhalate of women with pre-eclampsia and might be a volatile biomarker for amnionitis. Amniotic fluids analyzed by ion mobility spectrometry coupled with multi-capillary columns may provide bedside diagnosis of amnionitis and understanding inflammatory mechanisms during pregnancy.

Contribution of Uremia to Ureaplasma-Induced Hyperammonemia

Lung transplant recipients (LTRs) are vulnerable to unexplained hyperammonemia syndrome (HS) in the early post-operative period, a condition typically unresponsive to non-antibiotic interventions. Recently, we showed that HS in LTRs is strongly correlated with Ureaplasma infection of the respiratory tract. It is not well-understood what makes LTRs preferentially susceptible to this phenomenon, compared to other immunocompromised hosts. Ureaplasma species harbor highly active ureases that convert urea to ammonia and CO2, utilizing the generated transmembrane potential to synthesize ATP. Post-operative LTRs commonly experience renal failure, resulting in uremia. We hypothesized that uremia could be a potentiating comorbidity to the development of HS secondary to Ureaplasma infection in LTRs by providing increased substrate for ureaplasmal ureases. We designed a novel dialyzed flow system to test the ammonia producing capacity of four isolates of Ureaplasma parvum and six isolates of Ureaplasma urealyticum in media formulations relating to normal and uremic host conditions. For all isolates, growth under uremic conditions resulted in significantly increased ammonia production over 24 hours, despite similar end-point bacterial quantities. Specifically, the isolates produced, on average, 1776.52 [standard deviation=263.98] μmol/L more ammonia when grown under uremic compared to normal conditions. This suggests that uremia, common in early post-operative LTRs, is a plausible contributing factor to the phenomenon of Ureaplasma-induced HS in this patient population.