Antimicrobial resistance rates of urogenital Mycoplasma hominis and Ureaplasma species before and during the COVID-19 pandemic: results from a Greek survey, 2014 to 2022.

The prevalence of antibiotic-resistant urogenital mycoplasmas and ureaplasmas has been gradually increasing over the years, leading to greater concern for accurate diagnosis and treatment. In this study, the antimicrobial resistance trends in Greece were analyzed using 2992 Ureaplasma spp. and 371 M. hominis isolates collected between 2014 and 2022. Antibiotic sensitivity was determined using eight different antimicrobial agents (josamycin, pristinamycin, clindamycin, ofloxacin, azithromycin, tetracycline, erythromycin, and doxycycline), with the data analyzed using descriptive statistical methods. Resistance rates to clindamycin and erythromycin increased for both M. hominis and Ureaplasma spp., while remaining relatively low for Tetracycline, Doxycycline, and Ofloxacin. For Ureaplasma spp., high susceptibility was observed to pristinamycin, tetracycline, doxycycline, azithromycin, and josamycin, and intermediate susceptibility to erythromycin. However, the resistance rate for clindamycin dramatically increased from 60% in 2014 to a peak of 98.46% in 2021, and the erythromycin resistance rate increased from 9.54% in 2018 to 22.13% in 2021. M. hominis exhibited consistently high resistance rates to Erythromycin, while Azithromycin resistance significantly increased over time, from 52.78% in 2017 to 97.22% in 2022. The alarming escalation in antibiotic-resistant urogenital mycoplasmas and ureaplasmas in the Greek population is a significant concern. Antibiotic overconsumption may have played a crucial role in increasing resistance trends. The implementation of nationwide surveillance systems, proper antibiotic stewardship policies, and appropriate culture-based therapy policies are necessary to effectively control this emerging risk.

Preparation and evaluation in vitro and in vivo of pristinamycin enteric-coated granules based on albumin nanoparticles.

CONTEXT: The purpose of this study was to prepare enteric-coated particles based on albumin nanoparticles (NPs) using a mixture of PIA albumin NPs freeze-dried powder (PA-PIA) and PIIA albumin NPs freeze-dried powder (PA-PIIA) to improve the bioavailability effect of pristinamycin. OBJECTIVE: This is the first study on the preparation of pristinamycin into enteric-coated granules based on albumin NPs, and our study has effectively improved the bioavailability of pristinamycin and ensured its safety. METHODS: Pristinamycin albumin enteric-coated granules (PAEGs) were prepared by hybrid wet granulation. The characterizations of albumin NPs were performed by in vitro and in vivo studies of PAEGs. The assays were analyzed using zeta-sizer, transmission electron microscopy, high-performance liquid chromatography, and a fully automated biochemical index analyzer. RESULTS: The morphology of NPs was close to spherical. PIA-NPs and PIIA-NPs respectively had a zeta potential of (-24.33 ± 0.75) mV and (+7.30 ± 0.27) mV and mean size of (251.91 ± 19.64) nm and (232.83 ± 22.61) nm. The release of PIA and PIIA from PAEGs in the artificial gastrointestinal fluid was as high as 58.46% and 87.79%. In the experimental group of oral PAEGs, PIA and PIIA were AUC(0-t) (3.68 ± 0.58) mg·L-1·h-1 and (2.81 ± 1.06) mg·L-1·h-1. The results of aspartate aminotransferase and alanine aminotransferase biochemical indices showed that there was no significant difference between the experimental and normal groups of oral PAEGs. CONCLUSION: The PAEGs significantly increased the release of PIA and PIIA in simulated intestinal fluid and improved the bioavailability. The oral administration of PAEGs may not damage the liver of rats. We hope that our study will promote its industrial development or clinical application.

Genotypic characterization of vancomycin-resistant Enterococcus causing urinary tract infection in northern India.

Background & objectives: Infections caused by vancomycin-resistant Enterococci are difficult to treat given the limited therapeutic alternatives. Different gene clusters are known to confer vancomycin resistance. vanA and vanB genes are transferable and are clinically relevant. This cross-sectional study aimed to identify the vancomycin-resistant genotypes in the strains causing urinary tract infection and also to test the in vitro efficacy of linezolid and pristinamycin against the vancomycin-resistant isolates. Methods: Antimicrobial resistance profile of 118 enterococcal isolates was evaluated. Minimum inhibitory concentration of vancomycin, teicoplanin and high-level gentamicin (HLG) was determined by micro broth dilution. The vancomycin-resistant isolates were tested against linezolid and pristinamycin by micro-broth dilution and E strip method. The presence of vancomycin-resistant genes was detected by multiplex polymerase chain reaction and was sequenced and analyzed. Results: Most commonly isolated species were Enterococcus faecalis (76.9%) and Enterococcus faecium (16.9%). It was found that 43 per cent of the isolates were resistant to HLG and 16.9 per cent to vancomycin. Higher resistance was seen against fluoroquinolones, erythromycin, tetracycline and ß-lactam drugs. However, 5.08 per cent strains were resistant to tigecycline. All vancomycin-resistant strains were sensitive to pristinamycin and one was resistant to linezolid. vanA and vanB gene were found in 15 and five isolates, respectively. The gene sequences were submitted to NCBI gene bank and accession numbers were obtained. Interpretation & conclusions: The present study showed prevalence of vanA and vanB genes carrying Enterococcus in a tertiary care centre in north India. The emergence of resistance against drugs such as tigecycline and linezolid is a topic of concern as it will be a therapeutic challenge for physicians.

Results of patch testing in acute generalized exanthematous pustulosis (AGEP): A literature review.

The literature on positive patch-test results in acute generalized exanthematous pustulosis (AGEP) is reviewed. Ninety-three drugs were identified that have together caused 259 positive patch tests in 248 patients with AGEP. The drug classes causing the highest number of reactions are beta-lactam antibiotics (25.9%), other antibiotics (20.8%), iodinated contrast media (7.3%), and corticosteroids (5.4%), together accounting for nearly 60% of all reactions. The highest number of reactions to individual drugs was to amoxicillin (n = 36), followed by pristinamycin (n = 25), diltiazem (n = 14), amoxicillin-clavulanic acid (n = 13), clindamycin (n = 11), and iomeprol (n = 8); 59 of the 93 drugs each caused a single case only. The "Top-10" drugs together caused over 50% of all reactions. The sensitivity of patch testing (percentage of positive reactions) in patients with AGEP is largely unknown, but may generally be ~50%, which also applies to pristinamycin. Patch testing in AGEP appears to be safe, although mild recurrence of AGEP skin symptoms or other rashes may occur occasionally. Clinical aspects of AGEP, including epidemiology, etiology and pathophysiology, clinical features, histology, treatment, and prognosis are briefly presented, as are diagnosing the disease and identifying the culprit drugs with patch tests, intradermal tests, in vitro tests, and challenge tests.

Pristinamycin production using Streptomyces pristinaespiralis and date sirup as substrate-process modeling, optimization, and scale-up.

Pristinamycin biosynthesis using Streptomyces pristinaespiralis and date sirup (DS) as substrates was optimized before scale-up. DS was filter sterilized as heat sterilization primes Maillard reactions having negative effects on antibiotic production. Multilinear regression modeling (MLR) predicted optimum medium composition, specifying components with positive and negative effects on production. The MLR showed that to maximize bacterial growth, DS, arginine, CaCl2, and KH2PO4 must be fixed at the highest concentration, but to maximize antibiotic production, these factors have to be fixed at a low level. A noticeable difference in productivity was observed in a shake flask experiments with 50.4 and 43.1 mg/L pristinamycin final concentration for the DS and the glucose substrates, respectively. In the 2 L bioreactor, the DS medium resulted in a 66.6 mg/L antibiotic, while the scale-up in the 100 L resulted in 39.0 mg/L. The low yield in the 100 L bioreactor could be attributed to the relatively high stirring rate applied which was the minimum possible in the bioreactor used. This high stirring rate prevented pellet formation by the cells, which is described as necessary for antibiotic formation by the bacterium. Hence, a successful scale-up to pilot-scale should consider the effect of stirring rate.

Initial Failure of Pristinamycin Treatment in a Case of Multidrug-Resistant Mycoplasma genitalium Urethritis Eventually Treated by Sequential Therapy.

ABSTRACT: We present a case of persistent Mycoplasma genitalium urethritis with documented macrolide and fluoroquinolone resistance, and we describe the A2062T mutation in the 23S rRNA gene, possibly associated with pristinamycin resistance. After several treatment failures and loss of the A2062T mutation, M. genitalium urethritis was finally cured by a sequential antibiotic treatment including minocycline.

Streptogramins for the treatment of infections caused by Gram-positive pathogens.

INTRODUCTION: Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially multidrug-resistant isolates. AREAS COVERED: This review provides an updated overview of structural and activity characteristics, mechanisms of action and resistance, pharmacokinetic/pharmacodynamic, and clinical use of streptogramins. EXPERT OPINION: The streptogramin antibiotics act by inhibition of the bacterial protein synthesis. They are composed of two chemically distinct compounds, namely type A and type B streptogramins, which exert a rapid bactericidal activity against a wide range of Gram-positive bacteria (including methicillin-resistant staphylococci and vancomycin-resistant enterococci). Several mechanisms of resistance have been identified in staphylococci and enterococci but the prevalence of streptogramin resistance among clinical isolates remains very low. Even if only a few randomized clinical trials have been conducted, the efficacy of pristinamycin has been largely demonstrated with an extensive use for 50 years in France and some African countries. Despite its effectiveness in the treatment of severe Gram-positive bacterial infections demonstrated in several studies and the low rate of reported resistance, the clinical use of quinupristin-dalfopristin has remained limited, mainly due to its poor tolerance. Altogether, streptogramins (especially pristinamycin) can be considered as potential alternatives for the treatment of Gram-positive infections.

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

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

[Ulcerations of the extremities: An unusual manifestation of Behçet's disease]. / Ulcérations des extrémités : une manifestation inhabituelle de la maladie de Behçet.

BACKGROUND: Although cutaneous and mucosal involvement is a major manifestation in Behçet's disease, ulcerated lesions of the extremities are exceptional and poorly known. CASE REPORT: A 57-year-old male patient was diagnosed 7 years ago with Behçet's disease. This diagnosis was made in the presence of recurrent bipolar aphtous ulcers, pseudofolliculitis lesions and retinal vasculitis. After having been lost to follow up for two years, during which his treatment was discontinued, he presented centimetric necrotic ulcerations of the fingers of the hand and of the right big toe. The biopsy revealed leucocytoclastic and necrotizing vasculitis. The patient improved with antibiotic, oral corticosteroids, colchicine and local care. CONCLUSION: Linking extremity ulcers with Behçet's disease, though sometimes difficult, is essential for proper management.

Clinical Characteristics of Anorectal Mycoplasma genitalium Infection and Microbial Cure in Men Who Have Sex With Men.

BACKGROUND: We report clinical characteristics of proctitis caused solely by Mycoplasma genitalium (MG) compared with chlamydia and gonococcus. We determined the proportions cured with first-line (azithromycin) and second-line antimicrobials (moxifloxacin, pristinamycin). METHODS: A total of 166 patients attending Melbourne Sexual Health Centre from 2012 to 2016 with symptoms of proctitis were tested for MG, Chlamydia trachomatis, and Neisseria gonorrhoeae. Demographic characteristics, sexual behaviors, clinical symptoms, and signs were recorded. Multinomial multivariable logistic regression was used to test for significant differences in symptoms and signs for the pathogens detected. RESULTS: Seventeen percent of men had MG (95% confidence interval, 12-24), 21% had chlamydia (15-27), and 40% had gonococcal monoinfection (32-48), whereas 22% had MG coinfection (16-29). Relative to men with MG monoinfection, those with chlamydial monoinfection reported more anal pain (adjusted prevalence odds ratio (aPOR), 4.68 [1.41-14.19]), whereas men with gonococcal monoinfection reported more anal pain (aPOR, 6.75 [2.21-20.55]) and tenesmus (aPOR, 15.44 [1.62-146.90]), but less anal itch (aPOR, 0.32 [0.11-0.93]). The microbiological cure for MG using azithromycin was low at 35% (22-50), whereas moxifloxacin subsequently cured 92% (64-100) and pristinamycin cured 79% (54-94) of infections. CONCLUSIONS: M. genitalium was almost as common as chlamydia in men presenting to a sexual health center with symptoms of proctitis. Men with anorectal MG monoinfection were less likely to have symptoms and signs compared with those with chlamydia or gonococcus monoinfection. Cure for men with symptomatic anorectal MG by azithromycin was low. We suggest routine testing for MG in cases of proctitis, with test of cure after treatment being essential.

Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection.

High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.

Pristinamycin-induced arthralgia and myalgia: Analysis of the French Pharmacovigilance Database.

INTRODUCTION: Pristinamycin is an antibiotic of the streptogramin family; few adverse effects of this drug are reported, only cutaneous and digestive ones. Arthralgia and myalgia may however be observed although not mentioned in the summary of product characteristics. OBJECTIVE: Description and analysis of cases of pristinamycin-induced arthralgia and/or myalgia registered in the French database of pharmacovigilance. METHOD: We carried out a targeted search of the database, selecting case patients presenting with arthralgia and muscle pain and excluding those associated with sensitivities or allergies to pristinamycin. RESULTS: We retrieved 15 case patients of pristinamycin-induced arthralgia and myalgia. Pristinamycin was the only potentially incriminated drug for seven case patients. CONCLUSION: Although not serious, this adverse effect deserves to be better known by physicians to optimize therapeutic management.

Multianalyte Antibiotic Detection on an Electrochemical Microfluidic Platform.

The excessive use of antibiotics in human and veterinary medicine causes the emergence of multidrug resistant bacteria. In this context, the surveillance of many different antibiotics provokes a worldwide challenge. Hence, fast and versatile multianalyte single-use biosensors are of increasing interest for many fields such as medical analysis or environmental and food control. Here we present a microfluidic platform enabling the electrochemical readout of up to eight enzyme-linked assays (ELAs), simultaneously. To demonstrate the applicability of this platform for the surveillance and monitoring of antibiotics, we used highly sensitive biomolecular sensor systems for the simultaneous detection of two commonly employed antibiotic classes tetracycline and streptogramin. Thus, microfluidic channel networks are designed, comprising distinct numbers of immobilization sections with a very low volume of 680 nL each. These passively metered sections can be actuated separately for an individual assay procedure. The limits of detection (LOD) are determined, with high precision, to 6.33 and 9.22 ng mL-1 for tetracycline and pristinamycin, respectively. The employed channel material, dry film photoresist (DFR), allows an easy storage of preimmobilized assays with a shelf life of at least 3 months. Multianalyte measurements in a complex medium are demonstrated by the simultaneous detection of both antibiotics in spiked human plasma within a sample-to-result time of less than 15 min.