PMID- 29710295
OWN - NLM
STAT- MEDLINE
DCOM- 20180516
LR  - 20181114
IS  - 1538-3598 (Electronic)
IS  - 0098-7484 (Linking)
VI  - 319
IP  - 17
DP  - 2018 May 1
TI  - Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution
      of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical
      Trial.
PG  - 1781-1789
LID - 10.1001/jama.2018.3627 [doi]
AB  - 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.
FAU - Huttner, Angela
AU  - Huttner A
AD  - Infection Control Program, Geneva University Hospitals and Faculty of Medicine,
      Geneva, Switzerland.
AD  - Division of Infectious Diseases, Geneva University Hospitals and Faculty of
      Medicine, Geneva, Switzerland.
FAU - Kowalczyk, Anna
AU  - Kowalczyk A
AD  - Centre for Family and Community Medicine, Medical University of Lodz, Lodz,
      Poland.
FAU - Turjeman, Adi
AU  - Turjeman A
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Babich, Tanya
AU  - Babich T
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
FAU - Brossier, Caroline
AU  - Brossier C
AD  - Infection Control Program, Geneva University Hospitals and Faculty of Medicine,
      Geneva, Switzerland.
FAU - Eliakim-Raz, Noa
AU  - Eliakim-Raz N
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
AD  - Department of Internal Medicine E, Rabin Medical Center, Beilinson Campus,
      Peta-Tiqva, Israel.
FAU - Kosiek, Katarzyna
AU  - Kosiek K
AD  - Faculty of Health Sciences, Division of Public Health, Medical University of
      Lodz, Lodz, Poland.
FAU - Martinez de Tejada, Begona
AU  - Martinez de Tejada B
AD  - Obstetrics Division, Department of Obstetrics and Gynecology, Geneva University
      Hospitals and Faculty of Medicine, Geneva, Switzerland.
FAU - Roux, Xavier
AU  - Roux X
AD  - Department of Internal Medicine, Geneva University Hospitals and Faculty of
      Medicine, Geneva, Switzerland.
FAU - Shiber, Shachaf
AU  - Shiber S
AD  - Department of Emergency Medicine, Rabin Medical Center, Beilinson Campus,
      Peta-Tiqva, Israel.
FAU - Theuretzbacher, Ursula
AU  - Theuretzbacher U
AD  - Center for Anti-Infective Agents, Vienna, Austria.
FAU - von Dach, Elodie
AU  - von Dach E
AD  - Division of Infectious Diseases, Geneva University Hospitals and Faculty of
      Medicine, Geneva, Switzerland.
AD  - Clinical Trials Unit, Geneva University Hospitals and Faculty of Medicine,
      Geneva, Switzerland.
FAU - Yahav, Dafna
AU  - Yahav D
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
AD  - Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tiqva, 
      Israel.
FAU - Leibovici, Leonard
AU  - Leibovici L
AD  - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
AD  - Department of Internal Medicine E, Rabin Medical Center, Beilinson Campus,
      Peta-Tiqva, Israel.
FAU - Godycki-Cwirko, Maciek
AU  - Godycki-Cwirko M
AD  - Centre for Family and Community Medicine, Medical University of Lodz, Lodz,
      Poland.
AD  - Faculty of Health Sciences, Division of Public Health, Medical University of
      Lodz, Lodz, Poland.
FAU - Mouton, Johan W
AU  - Mouton JW
AD  - Department of Medical Microbiology and Infectious Diseases, Erasmus MC,
      Rotterdam, the Netherlands.
FAU - Harbarth, Stephan
AU  - Harbarth S
AD  - Infection Control Program, Geneva University Hospitals and Faculty of Medicine,
      Geneva, Switzerland.
AD  - Division of Infectious Diseases, Geneva University Hospitals and Faculty of
      Medicine, Geneva, Switzerland.
LA  - eng
SI  - ClinicalTrials.gov/NCT01966653
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - JAMA
JT  - JAMA
JID - 7501160
RN  - 0 (Anti-Infective Agents, Urinary)
RN  - 2N81MY12TE (Fosfomycin)
RN  - 927AH8112L (Nitrofurantoin)
SB  - AIM
SB  - IM
CIN - JAMA. 2018 May 1;319(17 ):1771-1772. PMID: 29710273
CIN - JAMA. 2018 Sep 25;320(12):1284. PMID: 30264107
CIN - Eur Urol. 2018 Nov;74(5):e124. PMID: 30318069
CIN - J Urol. 2018 Dec;200(6):1145. PMID: 30838915
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-Infective Agents, Urinary/adverse effects/*therapeutic use
MH  - Drug Administration Schedule
MH  - Drug Resistance, Bacterial
MH  - Female
MH  - Fosfomycin/*administration & dosage/adverse effects
MH  - Humans
MH  - Middle Aged
MH  - Nitrofurantoin/*administration & dosage/adverse effects
MH  - Treatment Outcome
MH  - Urinary Tract Infections/*drug therapy
MH  - Urine/microbiology
MH  - Young Adult
PMC - PMC6134435
EDAT- 2018/05/02 06:00
MHDA- 2018/05/17 06:00
CRDT- 2018/05/01 06:00
PHST- 2018/05/01 06:00 [entrez]
PHST- 2018/05/02 06:00 [pubmed]
PHST- 2018/05/17 06:00 [medline]
AID - 2679131 [pii]
AID - 10.1001/jama.2018.3627 [doi]
PST - ppublish
SO  - JAMA. 2018 May 1;319(17):1781-1789. doi: 10.1001/jama.2018.3627.