Review

Authors: Marzie Mahdizade Ari, Shirin Dashtbin, Fatemeh Ghasemi...

Nitrofurantoin (NF), a wide-spectrum antibiotic accessible since 1953, is utilized widely to treat urinary tract infections as it usually stays active against drug-resistant uropathogen. The use of Nitrofurantoin has increased exponentially since new guidelines have repositioned it as first-line therapy for uncomplicated lower urinary tract infection (UTI). To, although fluoroquinolones are usually used to re-evaluate the first- and second-line therapies for treating uncomplicated UTI, their level of utilization is thought to be inappropriately excessive and will eventually have a detrimental impact; thus, we hypothesize that NF might be the best choice for this condition, because of its low frequency of utilization and its high susceptibility in common UTI pathogens. It can be concluded from this review that NF can be considered as the most effective drug in the treatment of acute urinary infection, but due to the long-term side effects of this drug, especially in elderly patients, it is essential to introduce some criteria for prescribing NF in cases of chronic UTI.

Topics: Humans; Aged; Nitrofurantoin; Urinary Tract Infections; Anti-Bacterial Agents; Fluoroquinolones

PubMed: 37577377
DOI: 10.3389/fcimb.2023.1148603

Review

Authors: Raúl J Andrade, Guruprasad P Aithal, Ynto S de Boer...

Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarises the major topics discussed at a joint International Conference held between the Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and the condition often resolves spontaneously after withdrawal of the implicated drug, whereas patients with AIH mostly require long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow-up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements (such as Khat and Tinospora cordifolia) have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow for a precise diagnosis, while there is similarly no single feature which is diagnostic of AIH. We propose a management algorithm for patients with liver injury and an autoimmune phenotype. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterisation of this condition.

Topics: Humans; Chemical and Drug Induced Liver Injury; Hepatitis, Autoimmune; Nitrofurantoin; Congresses as Topic

PubMed: 37164270
DOI: 10.1016/j.jhep.2023.04.033

Comparative Study Randomized Controlled Trial

Authors: Angela Huttner, Anna Kowalczyk, Adi Turjeman...

IMPORTANCE

The use of nitrofurantoin and fosfomycin has increased since guidelines began recommending them as first-line therapy for lower urinary tract infection (UTI).

OBJECTIVE

To compare the clinical and microbiologic efficacy of nitrofurantoin and fosfomycin in women with uncomplicated cystitis.

DESIGN, SETTING, AND PARTICIPANTS

Multinational, open-label, analyst-blinded, randomized clinical trial including 513 nonpregnant women aged 18 years and older with symptoms of lower UTI (dysuria, urgency, frequency, or suprapubic tenderness), a positive urine dipstick result (with detection of nitrites or leukocyte esterase), and no known colonization or previous infection with uropathogens resistant to the study antibiotics. Recruitment took place from October 2013 through April 2017 at hospital units and outpatient clinics in Geneva, Switzerland; Lodz, Poland; and Petah-Tiqva, Israel.

INTERVENTIONS

Participants were randomized in a 1:1 ratio to oral nitrofurantoin, 100 mg 3 times a day for 5 days (n = 255), or a single 3-g dose of oral fosfomycin (n = 258). They returned 14 and 28 days after therapy completion for clinical evaluation and urine culture collection.

MAIN OUTCOMES AND MEASURES

The primary outcome was clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection). Secondary outcomes included bacteriologic response and incidence of adverse events.

RESULTS

Among 513 patients who were randomized (median age, 44 years [interquartile range, 31-64]), 475 (93%) completed the trial and 377 (73%) had a confirmed positive baseline culture. Clinical resolution through day 28 was achieved in 171 of 244 patients (70%) receiving nitrofurantoin vs 139 of 241 patients (58%) receiving fosfomycin (difference, 12% [95% CI, 4%-21%]; P = .004). Microbiologic resolution occurred in 129 of 175 (74%) vs 103 of 163 (63%), respectively (difference, 11% [95% CI, 1%-20%]; P = .04). Adverse events were few and primarily gastrointestinal; the most common were nausea and diarrhea (7/248 [3%] and 3/248 [1%] in the nitrofurantoin group vs 5/247 [2%] and 5/247 [1%] in the fosfomycin group, respectively).

CONCLUSIONS AND RELEVANCE

Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT01966653.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Fosfomycin; Humans; Middle Aged; Nitrofurantoin; Treatment Outcome; Urinary Tract Infections; Urine; Young Adult

PubMed: 29710295
DOI: 10.1001/jama.2018.3627

Authors: Naiqi Zhang, Yanni Li, Jan Sundquist...

BACKGROUND

Drug repurposing provides a cost-effective approach to address the need for breast cancer prevention and therapeutics. We aimed to identify actionable druggable targets using Mendelian randomization (MR) and then validate the candidate drugs using population-based analyses.

METHODS

We identified genetic instruments for 1406 actionable targets of approved non-oncological drugs based on gene expression, DNA methylation, and protein expression quantitative trait loci (eQTL, mQTL, and pQTL, respectively). Genome-wide association study (GWAS) summary statistics were obtained from the Breast Cancer Association Consortium (122,977 cases, 105,974 controls). We further conducted a nested case-control study using data retrieved from Swedish registers to validate the candidate drugs that were identified from MR analyses.

FINDINGS

We identified six significant MR associations with gene expression levels (TUBB, MDM2, CSK, ULK3, MC1R and KCNN4) and two significant associations with gene methylation levels across 21 CpG islands (RPS23 and MAPT). Results from the nested case-control study showed that the use of raloxifene (targeting MAPT) was associated with 35% reduced breast cancer risk (odds ratio, OR, 0.65; 95% confidence interval, CI, 0.51-0.83). However, usage of estradiol, tolterodine, and nitrofurantoin (also targeting MAPT) was associated with increased breast cancer risk, with adjusted ORs and 95% CI of 1.10 (1.07-1.13), 1.16 (1.09-1.24), and 1.09 (1.05-1.13), respectively. The effect of raloxifene and nitrofurantoin lost significance in further validation analyses using active-comparator and new-user design.

INTERPRETATION

This large-scale MR analysis, combined with population-based validation, identified eight druggable target genes for breast cancer and suggested that raloxifene is an effective chemoprevention against breast cancer.

FUNDING

Swedish Research Council, Cancerfonden, Crafoordska Stiftelsen, Allmänna Sjukhusets i Malmö Stiftelsen för bekämpande av cancer, 111 Project and MAS cancer.

Topics: Humans; Female; Breast Neoplasms; Case-Control Studies; Genome-Wide Association Study; Mendelian Randomization Analysis; Nitrofurantoin; Raloxifene Hydrochloride

PubMed: 38251461
DOI: 10.1016/j.ebiom.2023.104859

Comparative Study

Authors: Erika Y Lee, Tara Gomes, Aaron M Drucker...

IMPORTANCE

Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes.

OBJECTIVES

To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them.

DESIGN, SETTING, AND PARTICIPANTS

Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.

EXPOSURE

Various classes of oral antibiotics.

MAIN OUTCOMES AND MEASURES

Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group.

RESULTS

During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital.

CONCLUSION AND RELEVANCE

Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

Topics: Aged; Aged, 80 and over; Female; Humans; Male; Administration, Oral; Anti-Bacterial Agents; Case-Control Studies; Cephalosporins; Drug Eruptions; Emergency Service, Hospital; Fluoroquinolones; Hospitalization; Macrolides; Nitrofurantoin; Ontario; Penicillins; Sulfonamides; Risk Assessment

PubMed: 39115856
DOI: 10.1001/jama.2024.11437

Authors: Hala Alghoraibi, Aisha Asidan, Raneem Aljawaied...

BACKGROUND

Recurrent urinary tract infection (UTI) occurs in sizable percentages of patients after a single episode and is a frequent cause of primary healthcare visits and hospital admissions, accounting for up to one quarter of emergency department visits. We aim to describe the pattern of continuous antibiotic prophylaxis prescription for recurrent urinary tract infections, in what group of adult patients they are prescribed and their efficacy.

METHODS

A retrospective chart review of all adult patients diagnosed with single and recurrent symptomatic urinary tract infection in the period of January 2016 to December 2018.

RESULTS

A total of 250 patients with a single UTI episode and 227 patients with recurrent UTI episodes were included. Risk factors for recurrent UTI included diabetes mellitus, chronic renal disease, and use of immunosuppressive drugs, renal transplant, any form of urinary tract catheterization, immobilization and neurogenic bladder. E. coli infections were the most prevalent organism in patients with UTI episodes. Prophylactic antibiotics were given to 55% of patients with UTIs, Nitrofurantoin, Bactrim or amoxicillin clavulanic acid. Post renal transplant is the most frequent reason to prophylaxis antibiotics (44%). Bactrim was more prescribed in younger patients (P < 0.001), in post-renal transplantation (P < 0.001) and after urological procedures (P < 0.001), while Nitrofurantoin was more prescribed in immobilized patients (P = 0.002) and in patients with neurogenic bladder (P < 0.001). Patients who received continuous prophylactic antibiotics experienced significantly less episodes of urinary tract infections (P < 0.001), emergency room visits and hospital admissions due to urinary tract infections (P < 0.001).

CONCLUSION

Despite being effective in reducing recurrent urinary tract infection rate, emergency room visits and hospital admissions due to UTI, continuous antibiotic prophylaxis was only used in 55% of patients with recurrent infections. Trimethoprim/sulfamethoxazole was the most frequently used prophylactic antibiotic. Urology and gynecological referral were infrequently requested as part of the evaluation process for patients with recurrent UTI. There was a lack of use of other interventions such as topical estrogen in postmenopausal women and documentation of education on non-pharmacological methods to decrease urinary tract infections.

Topics: Humans; Adult; Female; Antibiotic Prophylaxis; Nitrofurantoin; Trimethoprim, Sulfamethoxazole Drug Combination; Escherichia coli; Retrospective Studies; Urinary Bladder, Neurogenic; Urinary Tract Infections; Anti-Bacterial Agents; Escherichia coli Infections; Risk Factors

PubMed: 37273158
DOI: 10.1007/s44197-023-00105-4

Authors: Vanessa Lopes, Joana Ramos, Patrícia Dias...

Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/μL of blood. Nitrofurantoin has been associated with haematological adverse events, but few agranulocytosis cases worldwide have been reported. We present a case of a 68-year-old woman who presented with fever and agranulocytosis following treatment with nitrofurantoin. Extensive workup for agranulocytosis, including a bone marrow aspirate, was unremarkable. Treatment with nitrofurantoin was discontinued, which led to a complete recovery of the complete blood count. This case stresses the importance of monitoring treatments, given that widely used drugs are not free from severe adverse reactions.

Topics: Aged; Blood Cell Count; Female; Humans; Leukocyte Count; Neutropenia; Neutrophils; Nitrofurantoin

PubMed: 34764131
DOI: 10.1136/bcr-2021-246788

Authors: A Huttner

Topics: Humans; Nitrofurantoin; Taboo

PubMed: 32454189
DOI: 10.1016/j.cmi.2020.05.011