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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 45376

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Prof. Dr. Riccardo Bartoletti

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Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
Interests: urinary tract infections; sexually transmitted diseases; genital infections; preoperative antibiotic prophylaxis; antibiotic stewardship

Special Issue Information

Dear Colleagues,

This issue of Antibiotics is dedicated to “difficult to treat infections” in urology. It includes clinically relevant topics such as catheter-associated urinary tract infections (CAUTI), recurrent cystitis, peri-procedural antimicrobial prophylaxis, and more.

Many infections in urology are caused by pathogens which are microbiologically difficult to characterize, and are thus clinically difficult to treat. These bacteria are involved not only in the infection process of urinary stones, but also in the case of transrectal prostate biopsy. This is a largely adopted procedure for the diagnosis of prostate cancer, but it is loaded by the high risk of developing sepsis.

The presence of “difficult to treat” bacterial biofilm on the surface of urological devices and catheters and worldwide increasing antimicrobial resistance are further complicating factors.

Fluoroquinolones are still the most frequently used antibiotics in the treatment of urinary tract infections. In most cases, they are immediately clinically effective. Furthermore, they are handy for both the urologist and the patient. The European Medical Agency (EMA) banned fluoroquinolones in March 2019, due to the high risk of developing adverse events, for many indications in daily urological practice. Moreover, bacterial antibiotic resistance against fluoroquinolones has increased significantly in several countries in recent years. The European Association of Urology Guidelines panel of urological infections has recently discussed this issue in a letter to the European Medical Agency, but several aspects remained unresolved. Antibiotic stewardship seems to be less applicable overall in the case of “difficult to treat infections”.

This Special Issue summarizes current knowledge of these aspects and offers the opportunity to face difficult to treat infections more efficiently. It is our pleasure to invite submissions of high-quality research manuscripts and review articles addressing the characterization of physiopathological aspects of these diseases and suggest adequate treatment by established drugs and/or novel compounds.

Prof. Riccardo Bartoletti
Guest Editor

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Keywords

Complicated urinary tract infections

Antibiotic Resistance

Fluoroquinolones therapy warning

Antibiotic prophylaxis in urology

Urinary stone disease treatment

Catheter associated urinary tract infections

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Published Papers (8 papers)

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9 pages, 268 KiB

Open AccessArticle

Comparison of Fluoroquinolones and Other Antibiotic Prophylaxis Regimens for Preventing Complications in Patients Undergoing Transrectal Prostate Biopsy

by Gabriele Tulone, Sofia Giannone, Piero Mannone, Alessio Tognarelli, Tommaso Di Vico, Rosa Giaimo, Alessandro Zucchi, Marta Rossanese, Alberto Abrate, Nicola Pavan, Francesco Claps, Vincenzo Ficarra, Riccardo Bartoletti and Alchiede Simonato

Antibiotics 2022, 11(3), 415; https://doi.org/10.3390/antibiotics11030415 - 20 Mar 2022

Cited by 6 | Viewed by 3405

Abstract

Our study aimed to compare the incidence of infective complications after transrectal ultrasound-guided prostate biopsy (TRUSBx) when adopting different antimicrobial prophylaxis regimens. A multi-institutional cohort of 1150 patients who underwent TRUSBx was retrospectively analyzed. Procedures were performed between 2017 and 2019 (before and after the EMA warning about the use of fluoroquinolones for the antibiotic prophylaxis of patient candidates to TRUSBx). The primary endpoint was the occurrence of infective complications, including sepsis and/or fever. The population was stratified according to the antibiotic prophylaxis adopted: fluoroquinolones (levofloxacin, ciprofloxacin, prulifloxacin), cephalosporins (cefixime, ceftriaxone) or trimethoprim/sulfamethoxazole. Univariable and multivariable binomial logistic regression models were used to assess the odds ratio (OR) with 95% confidence interval (CI) testing of the risk of infective complication after adjusting for each prebiopsy covariate. In total, 478 (41.6%) patients received fluoroquinolone-based prophylaxis. Among these, 443 (38.5%), 25 (2.2%) and 10 (0.9%) patients received levofloxacin prophylaxis, ciprofloxacin and prulifloxacin, respectively while 14.6% received cefixime, 20.7% received the comedication of ceftriaxone/fosfomycin and 23.1% received trimethoprim/sulfamethoxazole. The trimethoprim/sulfamethoxazole and fluoroquinolone regimens were significantly associated with a lower risk of infective complications (OR 0.15, 95% CI 0.03–0.48, p = 0.003 and OR 0.17, 95% CI 0.06–0.43, p < 0.001, respectively). The ceftriaxone/fosfomycin (OR 0.21, 95% CI 0.04–0.92, p = 0.04) and fluoroquinolone (OR 0.07, 95% CI 0.00–0.70, p = 0.048) prophylaxis were associated with a lower risk of infective sequelae. Fluoroquinolone-based prophylaxis was associated with a lower risk of infective complications after TRUSBx compared to other prophylaxis regimens although its clinical application was recently forbidden by European Medical Agency restrictions. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

15 pages, 3596 KiB

Open AccessArticle

Clinical Validation of the Greek Version of the Acute Cystitis Symptom Score (ACSS)—Part II

by Konstantinos Stamatiou, Evangelia Samara, Jakhongir F. Alidjanov, Adrian M. E. Pilatz, Kurt G. Naber and Florian M. E. Wagenlehner

Antibiotics 2021, 10(10), 1253; https://doi.org/10.3390/antibiotics10101253 - 15 Oct 2021

Cited by 4 | Viewed by 1885

Abstract

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) is the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different points in time after the start of treatment was demonstrated as well. The age (mean ± SD) of the 53 patients (44.7 ± 17.0 years) and 39 controls (49.3 ± 15.9 years) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p < 0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patients’ self-diagnosis of AC and as a PRO measure tool. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

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8 pages, 242 KiB

Open AccessArticle

Risk Indicators for Urinary Tract Infections in Low Risk Pregnancy and the Subsequent Risk of Preterm Birth

by Dominique E. Werter, Brenda M. Kazemier, Caroline Schneeberger, Ben W. J. Mol, Christianne J. M. de Groot, Suzanne E. Geerlings and Eva Pajkrt

Antibiotics 2021, 10(9), 1055; https://doi.org/10.3390/antibiotics10091055 - 31 Aug 2021

Cited by 9 | Viewed by 2851

Abstract

Symptomatic urinary tract infections are associated with preterm birth. However, data on risk indicators for urinary tract infections are limited and outdated. The research is a secondary analysis. The study was a prospective multicenter cohort study of low-risk pregnant women. Logistic regression was used to identify risk indicators for urinary tract infections. The incidence of urinary tract infections was 9.4%. Multivariate logistic regression showed that a history of recurrent urinary tract infections and the presence of asymptomatic bacteriuria in the present pregnancy were associated with urinary tract infections (resp. OR 3.14, 95%CI 1.40–7.02 and OR 1.96 95%CI 1.27–3.03). Women with a urinary tract infection were at increased risk of preterm birth compared to women without a urinary tract infection (12 vs. 5.1%; adjusted HR 2.5 95%CI 1.8–3.5). This increased risk was not found in women with the identified risk indicators (resp. 5.3% vs. 5.1%, adjusted HR 0.35 95%CI 0.00–420 and adjusted HR 1.5 95CI% 0.59–3.9). In conclusion, in low-risk pregnant women, risk indicators for urinary tract infections are: a history of recurrent urinary tract infections and the presence of asymptomatic bacteriuria. The risk of preterm birth is increased in women with a urinary tract infection in this pregnancy. However, women with recurrent urinary tract infections and asymptomatic bacteriuria this pregnancy appear not to be at increased risk of preterm birth. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

11 pages, 1761 KiB

Open AccessArticle

Treatment of Urinary Tract Infections with Canephron^® in Germany: A Retrospective Database Analysis

by Martina Höller, Hubert Steindl, Dimitri Abramov-Sommariva, Florian Wagenlehner, Kurt G. Naber and Karel Kostev

Antibiotics 2021, 10(6), 685; https://doi.org/10.3390/antibiotics10060685 - 8 Jun 2021

Cited by 18 | Viewed by 10504

Abstract

Objective: The goal of the present study was to evaluate treatment with Canephron^® compared to standard antibiotic treatment after diagnosis of acute cystitis or urinary tract infection (UTI), with regard to the risk of sporadic recurrent UTIs, frequent recurrent UTIs, UTI-related sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis). Methods: This retrospective cohort study was based on data from the IMS^® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron^® or standard antibiotics between January 2016 and June 2019 and treated in general practitioner (GP), gynecologist, or urologist practices, from which the data were obtained. Multivariable regression models were used to investigate the association between Canephron^® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI-related sick leave, the number of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron^® were adjusted for age, sex, insurance status, and Charlson comorbidity score (CCI). Results: 2320 Canephron^® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron^® prescription was significantly associated with fewer sporadic recurrences of UTI infections 30–365 days after the index date (odds ratio (OR): 0.66; 95%, confidence interval (CI): 0.58–0.72), as well as less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49–0.88), and also with reduced additional antibiotic prescription within 31–365 days (OR: 0.57; 95% CI: 0.52–0.63). No significant differences were observed between the Canephron^® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86–1.14), new antibiotic prescription within 1–30 days (OR: 1.01; 95% CI: 0.87–1.16), or occurrence of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67–1.48). Conclusion: These real-world data show that Canephron^® is an effective, safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment, particularly to also strengthen antimicrobial stewardship strategies. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

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Review

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14 pages, 12250 KiB

Open AccessReview

Genitourinary Tuberculosis: A Comprehensive Review of a Neglected Manifestation in Low-Endemic Countries

by Guglielmo Mantica, Francesca Ambrosini, Niccolò Riccardi, Enrico Vecchio, Lorenzo Rigatti, Aldo Franco De Rose, André Van der Merwe, Carlo Terrone, Riccardo Bartoletti and Gernot Bonkat

Antibiotics 2021, 10(11), 1399; https://doi.org/10.3390/antibiotics10111399 - 14 Nov 2021

Cited by 8 | Viewed by 6235

Abstract

Genitourinary tuberculosis (GUTB) represents a disease often underestimated by urological specialists, particularly in settings such as the European one, where the pathology is less frequent. Similar to other uncommon diseases at these latitudes, GUTB is a neglected clinical problem. In this light, the aim of this review is to give a comprehensive overview of GUTB in order to provide a useful tool for urologists who seldomly manage this disease. A non-systematic review of genitourinary tuberculosis was performed on relevant articles published from January 1990 to July 2021 using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. GUTB represents up to a quarter of extrapulmonary tuberculosis (EPTB) cases. Diagnostic, therapeutic and surgical work-up have been deeply reviewed and summarized. The mass migration of refugees to Europe as well as the ease of international travel is gradually leading to an upsurge in urological diseases such as GUTB, which were previously only rarely encountered in some European countries. The poor TB knowledge of European urologists should be improved through medical education courses, webinars or telematic means. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

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17 pages, 610 KiB

Open AccessReview

Treatment of UTIs Due to Klebsiella pneumoniae Carbapenemase-Producers: How to Use New Antibiotic Drugs? A Narrative Review

by Caroline Chapelle, Benjamin Gaborit, Raphaëlle Dumont, Aurélien Dinh and Maxime Vallée

Antibiotics 2021, 10(11), 1332; https://doi.org/10.3390/antibiotics10111332 - 1 Nov 2021

Cited by 13 | Viewed by 6122

Abstract

Background: K. pneumoniae is one of the bacteria most frequently causing health care-associated urinary tract infections, and increasingly incriminating Klebsiella pneumoniae carbapenemase producers (KPCp). Most infections caused by KPCp are nosocomial and might cause serious issues, even leading to death in half of the reported cases. Our aim was to identify the best strategy, based on available scientific data, for the use of new antibiotic treatments to manage KPCp UTIs. Methods: this narrative review of the literature was performed according to the criteria of preferred reporting items for systematic review and meta-analyses statement (PRISMA) (2020). Results and Conclusions: KPCp-UTIs are a real challenge for physicians. While cefiderocol, meropenem-vaborbactam, ceftazidim-avibactam, and imipenem-relebactam represent a major step forward in the treatment of these UTIs, no guidelines are currently available, in view of choosing the most appropriate treatment, in each specific case. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

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10 pages, 712 KiB

Open AccessReview

Use of Intravesical Injections of Platelet-Rich Plasma for the Treatment of Bladder Pain Syndrome: A Comprehensive Literature Review

by Francesco Trama, Ester Illiano, Alessandro Marchesi, Stefano Brancorsini, Felice Crocetto, Savio Domenico Pandolfo, Alessandro Zucchi and Elisabetta Costantini

Antibiotics 2021, 10(10), 1194; https://doi.org/10.3390/antibiotics10101194 - 1 Oct 2021

Cited by 11 | Viewed by 3559

Abstract

Background: Bladder pain syndrome/interstitial cystitis (BPS/IC) or primary bladder pain syndrome (PBPS) is a complex and poorly understood condition. This comprehensive review aimed to discuss the potential application of platelet-rich plasma (PRP) in the treatment of BPS/IC. The pathophysiology of BPS/IC is characterized by urothelial damage that triggers a chain of events leading to chronic inflammation and other conditions. Frequently, in subjects affected by BPS/IC, recurrent urinary tract infection (rUTI) is associated with difficult therapeutic management. For these reasons, many oral and intravesical treatments (e.g., antibiotic therapy and intravesical anesthetic instillations) have been proposed to alleviate the symptoms of IC/BPS. However, the limitation of these treatments is the short duration of improvement. The purpose of this review is to analyze the efficacy of intravesical PRP injections in subjects with PBS/IC and to try to understand the potential therapeutic effects on the pathophysiology of this disease. Methods: A nonsystematic literature search using Pubmed, EMBASE, Scopus, Web of Science, Medline was performed from January 2000 to August 2021. The following terms were combined to capture relevant publications: “platelet-rich plasma”, “interstitial cystitis”, “PRP”, “bladder pain syndrome”, and “painful bladder syndrome”. Results: After exclusion of non-pertinent studies/articles, we have analyzed 5 studies. In detail, 2 articles concerned preclinical studies in which animal models were used. The authors showed an improvement in the histological pattern with less bleeding in treated subjects, a lower presence of inflammatory cytokines and an increase in the mitotic index of urothelial cells in animals treated with intravesical PRP. In the three prospective clinical trials analyzed, patients with BPS/IC who underwent monthly intravesical PRP injections were found to have a statistically significant improvement in symptoms with modulation of growth factors and inflammatory proteins. Conclusions: New evidence suggests that treatment with intravesical PRP could improve urothelial regeneration and reduces chronic inflammation in BPS/IC, modifying the clinical history of its pathology. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

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10 pages, 261 KiB

Open AccessReview

Role of D-Mannose in the Prevention of Recurrent Uncomplicated Cystitis: State of the Art and Future Perspectives

by Cosimo De Nunzio, Riccardo Bartoletti, Andrea Tubaro, Alchiede Simonato and Vincenzo Ficarra

Antibiotics 2021, 10(4), 373; https://doi.org/10.3390/antibiotics10040373 - 1 Apr 2021

Cited by 24 | Viewed by 8597

Abstract

Background: Urinary tract infections (UTI) are highly frequent in women, with a significant impact on healthcare resources. Although antibiotics still represent the standard treatment to manage recurrent UTI (rUTI), D-mannose, an inert monosaccharide that is metabolized and excreted in urine and acts by inhibiting bacterial adhesion to the urothelium, represents a promising nonantibiotic prevention strategy. The aim of this narrative review is to critically analyze clinical studies reporting data concerning the efficacy and safety of D-mannose in the management of rUTIs. Methods: A non-systematic literature search, using the Pubmed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases, was performed for relevant articles published between January 2010 and January 2021. The following Medical Subjects Heading were used: “female/woman”, “urinary tract infection”, and “D-mannose”. Only clinical studies, systematic reviews, and meta-analyses reporting efficacy or safety data on D-mannose versus placebo or other competitors were selected for the present review. Evidence was limited to human data. The selected studies were organized in two categories according to the presence or not of a competitor to D-mannose. Results: After exclusion of non-pertinent studies/articles, 13 studies were analyzed. In detail, six were randomized controlled trials (RCTs), one a randomized cross-over trial, five prospective cohort studies, and one a retrospective analysis. Seven studies compared D-mannose to placebo or others drugs/dietary supplements. Six studies evaluated the efficacy of D-mannose comparing follow-up data with the baseline. D-mannose is well tolerated, with few reported adverse events (diarrhea was reported in about 8% of patients receiving 2 g of D-mannose for at least 6 months). Most of the studies also showed D-mannose can play a role in the prevention or rUTI or urodynamics-associated UTI and can overlap antibiotic treatments in some cases. The possibility to combine D-mannose with polyphenols or Lactobacillus seems another important option for UTI prophylaxis. However, the quality of the collected studies was very low, generating, consequently, a weak grade of recommendations as suggested by international guidelines. Data on D-mannose dose, frequency, and duration of treatment are still lacking. Conclusion: D-mannose alone or in combination with several dietary supplements or Lactobacillus has a potential role in the non antimicrobial prophylaxis or recurrent UTI in women. Despite its frequent prescription in real-life practice, we believe that further well-designed studies are urgently needed to definitively support the role of D-mannose in the management of recurrent UTIs in women. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

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