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Clinical Microbiology and Infection :... Oct 2023Urinary tract infections (UTIs) are the most common infection among pregnant women and have been associated with maternal and foetal complications. Antimicrobial... (Review)
Review
BACKGROUND
Urinary tract infections (UTIs) are the most common infection among pregnant women and have been associated with maternal and foetal complications. Antimicrobial exposure during pregnancy is not without risk. International guidelines recommend a single screen-and-treat approach to asymptomatic bacteriuria (ASB); however, this approach has been questioned by recent studies.
OBJECTIVES
The aim of this narrative review was to assess the pathophysiology, current risk factors and management of UTI during pregnancy, its impact on pregnancy outcomes, and to develop recommendations on the best use of antimicrobials.
SOURCES
PubMed, Cochrane database, and ClinicalTrials.gov.
CONTENT
Owing to the physiological changes related to pregnancy, pregnant women are at higher risk of UTI. All types of UTIs combined have been estimated to affect approximately 2% to 15% of women. ASB affects 2% to 7% of pregnant women. Recent studies do not provide good-quality evidence for an association between ASB and acute pyelonephritis if ASB is untreated. There is low-to-moderate-quality evidence that treatment of ASB results in a reduction in the incidence of low birth weight and preterm birth, which justifies screening practices for ASB with only a single urine culture in the first trimester. If the clinician opts for treatment, a short course of β-lactams, nitrofurantoin, or fosfomycin should be favoured. Studies on cystitis during pregnancy are limited. Acute pyelonephritis has been shown to be associated with increased maternal complications and in some studies has also been associated with preterm delivery and low birth weight. Preferred antimicrobials for the management of pyelonephritis are amoxicillin combined with an aminoglycoside, third-generation cephalosporins, or carbapenems. Studies on recurrent UTIs during pregnancy are limited, making it difficult to draw conclusions regarding prophylactic measures.
IMPLICATIONS
Further research is required to understand the true incidence of ASB-related complications and the benefit and modalities of screening for ASB and to further explore prophylactic measures.
Topics: Female; Pregnancy; Infant, Newborn; Humans; Pregnancy Complications, Infectious; Premature Birth; Urinary Tract Infections; Bacteriuria; Anti-Bacterial Agents; Pyelonephritis; Pregnancy Outcome
PubMed: 36031053
DOI: 10.1016/j.cmi.2022.08.015 -
The New England Journal of Medicine Feb 2024Carbapenem-resistant Enterobacterales species and multidrug-resistant are global health threats. Cefepime-taniborbactam is an investigational β-lactam and β-lactamase... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Carbapenem-resistant Enterobacterales species and multidrug-resistant are global health threats. Cefepime-taniborbactam is an investigational β-lactam and β-lactamase inhibitor combination with activity against Enterobacterales species and expressing serine and metallo-β-lactamases.
METHODS
In this phase 3, double-blind, randomized trial, we assigned hospitalized adults with complicated urinary tract infection (UTI), including acute pyelonephritis, in a 2:1 ratio to receive intravenous cefepime-taniborbactam (2.5 g) or meropenem (1 g) every 8 hours for 7 days; this duration could be extended up to 14 days in case of bacteremia. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 to 23 in the microbiologic intention-to-treat (microITT) population (patients who had a qualifying gram-negative pathogen against which both study drugs were active). A prespecified superiority analysis of the primary outcome was performed after confirmation of noninferiority.
RESULTS
Of the 661 patients who underwent randomization, 436 (66.0%) were included in the microITT population. The mean age of the patients was 56.2 years, and 38.1% were 65 years of age or older. In the microITT population, 57.8% of the patients had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Composite success occurred in 207 of 293 patients (70.6%) in the cefepime-taniborbactam group and in 83 of 143 patients (58.0%) in the meropenem group. Cefepime-taniborbactam was superior to meropenem regarding the primary outcome (treatment difference, 12.6 percentage points; 95% confidence interval, 3.1 to 22.2; P = 0.009). Differences in treatment response were sustained at late follow-up (trial days 28 to 35), when cefepime-taniborbactam had higher composite success and clinical success. Adverse events occurred in 35.5% and 29.0% of patients in the cefepime-taniborbactam group and the meropenem group, respectively, with headache, diarrhea, constipation, hypertension, and nausea the most frequently reported; the frequency of serious adverse events was similar in the two groups.
CONCLUSIONS
Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem. (Funded by Venatorx Pharmaceuticals and others; CERTAIN-1 ClinicalTrials.gov number, NCT03840148.).
Topics: Adult; Aged; Humans; Middle Aged; Administration, Intravenous; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Borinic Acids; Carboxylic Acids; Cefepime; Drug Therapy, Combination; Hospitalization; Meropenem; Microbial Sensitivity Tests; Pyelonephritis; Urinary Tract Infections; Drug Resistance, Bacterial
PubMed: 38354140
DOI: 10.1056/NEJMoa2304748 -
Obstetrics and Gynecology Aug 2023Urinary tract infection (UTI) is one of the more common perinatal complications, affecting approximately 8% of pregnancies (1, 2). These infections represent a spectrum,...
Urinary tract infection (UTI) is one of the more common perinatal complications, affecting approximately 8% of pregnancies (1, 2). These infections represent a spectrum, from asymptomatic bacteriuria, to symptomatic acute cystitis, to the most serious, pyelonephritis. The presence of UTIs has been associated with adverse pregnancy outcomes, including increased rates of preterm delivery and low birth weight. Screening for and treating asymptomatic bacteriuria have been shown in multiple studies to reduce the incidence of pyelonephritis in pregnancy (3-5). Given the frequency at which UTIs are encountered in pregnancy, the ability to recognize, diagnose, and treat them is essential for those providing care to pregnant individuals. This Clinical Consensus document was developed using an established protocol in conjunction with the authors listed.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Bacteriuria; Pregnancy Complications, Infectious; Urinary Tract Infections; Pyelonephritis; Cystitis; Anti-Bacterial Agents
PubMed: 37473414
DOI: 10.1097/AOG.0000000000005269 -
Drugs Jun 2024Cefepime/enmetazobactam (EXBLIFEP), an intravenous (IV) antibacterial fixed-dose combination of a 4th generation cephalosporin and an extended-spectrum β-lactamase... (Review)
Review
Cefepime/enmetazobactam (EXBLIFEP), an intravenous (IV) antibacterial fixed-dose combination of a 4th generation cephalosporin and an extended-spectrum β-lactamase (ESBL) inhibitor, is being developed by Allecra Therapeutics and ADVANZ PHARMA for the treatment of infections caused by multi-drug-resistant (MDR) Gram-negative bacteria. In February 2024, cefepime/enmetazobactam was approved in the USA for use in adults with complicated urinary tract infections (cUTI) including pyelonephritis, caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex. In March 2024, cefepime/enmetazobactam was approved in the EU for use in adults for the treatment of cUTI, including pyelonephritis, and hospital-acquired pneumonia, including ventilator associated pneumonia, and the treatment of patients with bacteraemia occurring in association with or suspected to be associated with any of these infections. This article summarizes the milestones in the development of cefepime/enmetazobactam leading to this first approval for the treatment of adults with infections caused by MDR Gram-negative bacteria.
Topics: Humans; Cefepime; Anti-Bacterial Agents; Urinary Tract Infections; Drug Approval; Gram-Negative Bacterial Infections; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Cephalosporins; beta-Lactamase Inhibitors; United States; Drug Combinations; Pyelonephritis
PubMed: 38761353
DOI: 10.1007/s40265-024-02035-2 -
Radiographics : a Review Publication of... May 2024
Topics: Humans; Pyelitis
PubMed: 38635453
DOI: 10.1148/rg.240002 -
Nature Reviews. Nephrology Oct 2023Urinary tract infections (UTIs) are among the most common bacterial infections seen in clinical practice. The ascent of UTI-causing pathogens to the kidneys results in... (Review)
Review
Urinary tract infections (UTIs) are among the most common bacterial infections seen in clinical practice. The ascent of UTI-causing pathogens to the kidneys results in pyelonephritis, which can trigger kidney injury, scarring and ultimately impair kidney function. Despite sizable efforts to understand how infections develop or are cleared in the bladder, our appreciation of the mechanisms by which infections develop, progress or are eradicated in the kidney is limited. The identification of virulence factors that are produced by uropathogenic Escherichia coli to promote pyelonephritis have begun to fill this knowledge gap, as have insights into the mechanisms by which kidney tubular epithelial cells oppose uropathogenic E. coli infection to prevent or eradicate UTIs. Emerging data also illustrate how specific cellular immune responses eradicate infection whereas other immune cell populations promote kidney injury. Insights into the mechanisms by which uropathogenic E. coli circumvent host immune defences or antibiotic therapy to cause pyelonephritis is paramount to the development of new prevention and treatment strategies to mitigate pyelonephritis and its associated complications.
Topics: Humans; Escherichia coli; Pyelonephritis; Kidney; Epithelial Cells
PubMed: 37479904
DOI: 10.1038/s41581-023-00737-6 -
Clinical Imaging Dec 2023Various infectious and inflammatory diseases affect the genitourinary system. This paper provides a review of multiple common and uncommon infectious and inflammatory... (Review)
Review
Various infectious and inflammatory diseases affect the genitourinary system. This paper provides a review of multiple common and uncommon infectious and inflammatory conditions affecting the genitourinary system and some associated complications. These include acute infectious cystitis, emphysematous cystitis, acute pyelonephritis, emphysematous pyelonephritis, renal and perinephric abscesses, pyonephrosis, xanthogranulomatous pyelonephritis, epididymo-orchitis, vasitis, prostatitis, pelvic inflammatory disease, renal hydatid infection, renal tuberculosis, actinomycosis, Erdheim-Chester Disease, IgG4-Related Kidney Disease, urethritis and urethral strictures, ureteritis cystica, and genitourinary fistulas. Radiologists should be aware of these diseases' complications and management. Uncommon conditions must be considered when evaluating the genitourinary system.
Topics: Male; Humans; Inflammation; Urogenital System; Pyelonephritis; Urinary Tract Infections; Kidney Diseases; Cystitis
PubMed: 37918136
DOI: 10.1016/j.clinimag.2023.110013 -
Medicina (Kaunas, Lithuania) Sep 2023Diabetes mellitus is a chronic disease that, untreated or poorly controlled, can lead to serious complications, reducing life expectancy and quality. Diabetic patients... (Review)
Review
Diabetes mellitus is a chronic disease that, untreated or poorly controlled, can lead to serious complications, reducing life expectancy and quality. Diabetic patients are more likely to develop infections, including many common infections, but also pathognomonic ones such as emphysematous pyelonephritis, malignant otitis externa, mucormycosis and Fournier's gangrene. Considering the fact that diabetic patients experience more frequently urinary tract infections (UTIs) with a worse prognosis than non-diabetic people, we conducted a review study based on data in the literature, following the particularities of UTIs in this group of patients, the risk factors, the mechanisms involved and the challenges in their management. The findings highlight that UTI in diabetic patients have some particularities, including a more frequent evolution to bacteremia, increased hospitalizations, and elevated rates of recurrence and mortality than non-diabetic patients. The possible risk factors identified seem to be female gender, pregnancy, older age, UTI in the previous six months, poor glycemic control and duration of diabetes. The mechanisms involved are related to glucosuria and bladder dysfunction, factors related to bacterial strains and host response. The bacterial strains involved in UTIs in diabetic patients and their antibiotic susceptibility profile are, with some exceptions, similar to those in non-diabetic people; however, the antimicrobial agents should be carefully chosen and the duration of the treatment should be as those required for a complicated UTI. The data related to the risk of developing UTIs in patients treated with SGLT-2 inhibitors, a new class of oral hypoglycaemic agents with cardiovascular and renal benefits, are controversial; overall, it was evidenced that UTIs occurred at the initiation of the treatment, recurrent infection was uncommon and the majority of UTIs responded to treatment with standard antibiotics. Moreover, interruption or discontinuation of SGLT-2 inhibitor as a result of UTI was rare and SGLT-2 inhibitors did not increase the risk of severe infections such as urosepsis and pyelonephritis.
Topics: Pregnancy; Humans; Female; Sodium-Glucose Transporter 2 Inhibitors; Urinary Tract Infections; Diabetes Mellitus; Pyelonephritis; Anti-Bacterial Agents
PubMed: 37893465
DOI: 10.3390/medicina59101747 -
Clinical Microbiology and Infection :... Oct 2023Given the high frequency of patients presenting with urinary tract infections (UTIs) and the ensuing high degree of antibiotic prescription, UTI is a critical point of... (Review)
Review
BACKGROUND
Given the high frequency of patients presenting with urinary tract infections (UTIs) and the ensuing high degree of antibiotic prescription, UTI is a critical point of intervention for non-antibiotic treatments to curb the further development of antimicrobial resistance and provide risk-appropriate care for patients.
OBJECTIVES
To highlight several select non-antibiotic therapies for the treatment of uncomplicated UTI and relevant indications (prevention and complicated UTI) from recent literature.
SOURCES
PubMed, Google Scholar, and clinicaltrials.gov were searched for clinical trials published in the English language corresponding to non-antibiotic treatments for UTI.
CONTENT
The focus of this narrative review centres on a limited number of non-antibiotic therapies for the treatment of UTI based on (a) herbal extracts or (b) antibacterial strategies (e.g. bacteriophage therapy and D-mannose). The experience of treatment with non-steroidal anti-inflammatory drugs is also used to fuel discussion on the risk of developing pyelonephritis without antibiotics-compared with the projected harms of continuing their widespread use.
IMPLICATIONS
Non-antibiotic treatment strategies for UTI have shown varying results in clinical trials, and the current evidence does not yet indicate a clear, better alternative to antibiotics. However, the collective experience with non-antibiotic treatments suggests that there is a need to weigh the actual benefits/risks of unfettered, non-culture-confirmed antibiotic use in uncomplicated UTI. Given the different mechanisms of action of proposed alternatives, more in-depth knowledge on microbiological and pathophysiological factors influencing UTI susceptibility and prognostic indicators are highly needed to stratify patients most likely to benefit. The feasibility of alternatives in clinical practice should also be considered.
Topics: Humans; Anti-Bacterial Agents; Urinary Tract Infections; Pyelonephritis; Anti-Inflammatory Agents, Non-Steroidal; Prescriptions
PubMed: 37301438
DOI: 10.1016/j.cmi.2023.06.001