Presencia de agentes infrecuentes de infección en el aparato genitourinario en atención sanitaria especializada

Résumé

INTRODUCTION The etiological agents related to genitourinary infections have been widely described, such as enterobacteria, enterococci, Pseudomonas spp., Acinetobacter spp., Candida spp., etc., as well as the empirical diagnosis and treatment protocols. However, more and more frequently, new microorganisms are being detected and recognized that until a few years ago were considered "contaminants" of the sample, not being correctly identified, or could not be isolated because they are demanding with the usual growth conditions in the culture media. This type of microorganisms is gaining great importance when isolated in the absence of the main causative agents of genitourinary infectious pathology, so they can have great clinical and microbiological significance. The increase in the pluripathological population, as well as the early initiation of sexual relations by adolescents and changes in the general lifestyle due to the evolution of today's society, has favored the appearance of risk factors that promote its development. Among these microorganisms, we highlight at the genital level the species of Haemophilus no ducreyi (HND) and at the genitourinary level Corynebacterium spp., Aerococcus spp., Actinotignum spp., Actinobaculum massiliense, Actinomyces turicensis, Alloscardovia omnicolens, Aeromonas hydrophila, Eikenella corrodens, Lactobacillus spp., Streptococcus bovis group (SBG), pneumoniae and viridans group (SVG), Leptotrichia trevisanii, Facklamia spp., Pasteurella spp., Neisseria meningitidis and Gardnerella vaginalis. The detection and identification of these new and infrequent microbiological agents opens up a new range of possibilities in addition to the typical and known pathogens, and could mean a change in the paradigm of management of this type of infection, especially with regard to classical empirical antibiotic treatment, since resistance to some antibiotics has been identified. This study intends to relate the identification of these microorganisms in urinary and genital samples with the clinical manifestations, therapeutic attitude and evolution of the subject at the time of obtaining the sample, as well as trying to identify epidemiological or clinical factors that may act as favoring factors for the growth of said etiological agents. In addition, a systematic review has been carried out on the clinical relevance of Haemophilus no ducreyi and other emerging microorganisms at the genitourinary level. METHODOLOGY The articles that make up this doctoral thesis are divided into two parts: on the one hand, the analysis of the presence and clinical relevance of Haemophilus non ducreyi in genital samples and, on the other hand, the clinical importance of other emerging microorganisms at the genitourinary level. Regarding the methodology used, they are explained separately according to the types of study and article included: - Systematic review: for this doctoral thesis, two systematic reviews have been carried out: clinical importance of the isolation of Haemophilus spp. (excluding H. ducreyi) in genital samples and a systematic review of the publications on the participation of other emerging microorganisms in infections of the genitourinary system. - Study on Haemophilus no ducreyi: descriptive cross-sectional study based on genital samples analyzed in the Microbiology Laboratory of the Virgen de las Nieves University Hospital in Granada between 2016 and 2019, analyzing epidemiological, microbiological and clinical variables and separating between males on the one hand and women and girls on the other. In addition, two cases of urethritis due to H. sputorum and H. pittmaniae are described in a separate article. - Study of other emerging microorganisms at the genitourinary level: descriptive crosssectional study where, based on the results obtained from urine samples and genital exudates of men and women between January 2016 and December 2019, their epidemiological and clinical characteristics were collected and analyzed, as well as the antibiotic treatments used and their evolution. Regarding the study of symptomatic bacteriospermia episodes, the time period was extended to May 2021. RESULTS - Clinical significance of isolation of Haemophilus no ducreyi in genital samples. Systematic review: after reviewing what was described in the literature, Haemophilus spp. (excluding H. ducreyi: HND) was detected in 2397 episodes of genital infection, the most frequently isolated species being H. influenzae and H. parainfluenzae. Most of the episodes (87.6%) are constituted by single isolation. There is a slight predominance in women (48.3%) where it can cause vaginitis, salpingitis, endometritis or complications during pregnancy. In men, the clinical picture usually corresponds to urethritis. Most of the samples correspond to vaginal and urethral exudates, with a minority representation at the rectal level (2.3%). - Isolation of Haemophilus no ducreyi in samples from the genital tract of men: its clinical relationship: HND was isolated in 135 (7%) of the genital infection episodes diagnosed in men. H. parainfluenzae was the most commonly isolated (34/45; 75.6%). The most frequent symptoms in men with proctitis were rectal tenesmus (31.6%) and lymphadenopathy (10.5%); in those with urethritis, dysuria (71.6%), urethral suppuration (46.7%) and gland lesions (27%), so differentiating it from infections caused by other genitopathogens is difficult. 43% of patients were HIV positive. Antibiotic resistance rates for H. parainfluenzae were high to quinolons, ampicillin, tetracycline and macrolides. - Importance of the role of Haemophilus no ducreyi isolates in female genital tract and its clinical relationship: 45 (25 women and 20 girls) isolates of HND were found, corresponding to 1%; the most frequent specie was Haemophilus influenzae (64.4%). In women, leukorrhea and abdominal pain was frequent and in 72% there was a polymicrobial isolate. In girls, it was frequently in isolation, with the presence of vulvovaginal erythema, pathological discharge, and local itching. We highlight the high rate of resistance of Haemophilus parainfluenzae to azithromycin (72.7%) and cotrimoxazole (18.2%) in adult women, in contrast to resistance to azithromycin in girls (25%). - Emergence of genital infections due to Haemophilus pittmaniae and Haemophilus sputorum: description of two cases of urethritis secondary to those species of HND in our hospital Emerging presence of culturable microorganisms in clinical samples of the genitourinary system: systematic review and experience in Specialized Care of a regional hospital: the review highlighted the frequent involvement of Neisseria meningitidis in genital infections, while the data on other microorganisms were consistent with findings in our patient series. The emerging microorganisms most often responsible for urinary tract infections were Streptococcus bovis (58.5%) and Gardnerella vaginalis (23.6%) in females, and S. bovis (32.3%), Aerococcus urinae (18.6%), and Corynebacterium spp. (16.9%) in males; those most frequently reported in genital infections were S. viridans (36.4%) in females and C. glucuronolyticum (32.2%) and G. vaginalis (35.6%) in males. In general, emerging pathogens are resistant to conventional antibiotics such as penicillin. However, there has also been an increase in betalactam resistance by the S. bovis group and Corynebacterium spp. - Presence and relevance of emerging microorganisms in clinical genitourinary samples: Symptomatic episodes were more frequent with Aerococcus spp. and S. bovis and the presence of leukocytosis more frequent with Aerococcus spp. Quinolones and doxycycline were most often prescribed antibiotics for genital infections and quinolones and amoxicillinclavulanic acid for urinary infections. - Antibiotic resistance changes in episodes of symptomatic bacteriospermia: development in a health area of southeast Spain: The main isolated microorganism is Enterococcus faecalis (34.89%), followed by Ureaplasma spp. (13.74%) and Escherichia coli (10.98%). Corynebacterium spp. was the fourth most frequently isolated group of microorganisms (21/5.77%). Emerging microorganisms were responsible for approximately 10% of the cases, highlighting the importance of knowing them in order to establish adequate empirical and directed antibiotic treatment in these conditions. CONCLUSIONS 1. HND species play a relevant pathogenic role in episodes of genital infection, so microbiological diagnostic protocols must include methods that allow their detection, as well as include them in the etiological spectrum of this type of clinical entities. In the systematic review, the most frequent specie was H. influenzae, with urethritis predominating in men; in pregnant women, septic abortion, chorioamnionitis and premature rupture of membranes and in non-pregnant women, vaginitis and upper genital infections. There are few descriptions of its presence in rectal samples. 2. In our study, we found a high prevalence of human immunodeficiency virus infection and previous sexually transmitted infections in men with urethritis and proctitis due to HND. Therefore, it should not be forgotten in cases of urethritis and/or proctitis in men with HIV infection and/or previous risky sexual relations with negative screening tests for common agents. In adult women they can be the cause of vaginitis, cervicitis and pelvic inflammatory disease. In girls, H. influenzae represents one of the microbiological agents of vulvovaginal infections. The rate of resistance to azithromycin in H. parainfluenzae and to cotrimoxazole in both species should be kept in mind. 3. Emerging microorganisms are responsible for a small percentage of episodes of genitourinary infections, but are of mayor clinical interest. They should be suspected in the presence of certain favorable factors that increase the probability of infection by these agents, such as anatomical alterations of the urinary tract or prostate, indwelling urinary catheter, solid organ transplantation, diabetes mellitus, pharmacological immunosuppression or use of antibiotics in the previous three months. In the systematic review, we highlight the role of Neisseria meningitidis in genital infections, describing more and more cases. 4. In our study, we highlight the higher frequency of urinary tract infection due to Aerococcus in in males of advanced age, the association of Corynebacterium with permanent vesical catheter carriers, and the greater presence of episodes of asymptomatic bacteriuria due to G. vaginalis in kidney transplant and chronic consumers of corticosteroid therapy. Lactobacillus spp. should be considered in urinary infections of patients of advanced age and with a previous antibiotic load. Genital infection by Gardnerella spp. was significantly associated with a history of risky sexual relations. Due to the increase in resistance to antibiotics used empirically in genitourinary infections, it is vitally important to carry out an antibiogram and clinical suspicion to establish an adequate targeted treatment.