- The study examined 183 geriatric hip fracture patients to determine the prevalence of urinary tract infection (UTI) on admission and whether routine screening for UTI led to reduced rates of catheter-associated UTI (CAUTI).
- 36.1% of patients had a UTI on admission based on urinalysis screening. 4.4% of patients developed CAUTI.
- Patients with UTI on admission had a significantly longer median ICU length of stay compared to those without UTI on admission. No other significant differences were found between groups.
2. 2010). The Centers for Medicare & Medicaid has deemed
that CAUTI is a “reasonably preventable” inhospital com-
plication and has terminated reimbursements for these
events since 2008 (CDC, 2019). The mean cost of UTI is
$862 to $1007 per UTI (Bail et al., 2015; CDC, 2019; Scott,
2010), whereas a systematic review found that the mean
cost of CAUTI can exceed $10,000 per CAUTI based on
the clinical status of the patient (Hollenbeak & Schilling,
2018).
A vast majority of patients who suffer hip fractures
undergo a surgical repair after admission (Bliemel et al.,
2017; Johnstone, Morgan, Wilkinson, & Chissell, 1995;
Wallace et al., 2019). These repairs have an elevated risk
of causing postoperative urinary retention due to the
ABSTRACT
Background: Catheter-associated urinary tract infection
(CAUTI) is a noted complication among geriatric hip fracture
patients. This complication results in negative outcomes
for both the patients and the institution providing care.
Screening measures to identify predisposing factors, with
early diagnosis and treatment of urinary tract infection (UTI)
present on admission, may lead to reduced rates of CAUTI.
Objective: The goals of this study were to determine the
prevalence of UTI on admission among geriatric hip fracture
patients and whether routine screening for UTI or predisposing
factors at presentation resulted in reduced rates of CAUTI.
Methods: A retrospective observational study of geriatric hip
fracture patients from January 2017 to December 2018 at a
Level I trauma center was performed. Rates of UTI on
admission
and CAUTI were calculated using routine admission urinalysis.
Results: Of the 183 patients in the sample, 36.1% had UTI
on admission and 4.4% of patients developed CAUTI. There
3. were no significant differences in patient demographics,
comorbidities, and complications between those with UTI on
admission and those without.
Conclusions: Urinary tract infection on admission may
be present among a large portion of geriatric hip fracture
patients, leading to increased rates of CAUTI. Routine
screening for UTI and its predisposing factors at admission
can identify these patients earlier and lead to earlier
treatments and prevention of CAUTI.
Key Words
Catheter-associated urinary tract infections, CAUTI,
Complications, Elderly, Geriatric, Hip fracture, Hospital costs,
Trauma, Urinary tract infections
Author Affiliation: Department of Surgery, Nassau University
Medical
Center, East Meadow, New York.
The content of this article does not substantially overlap with
previously
published or submitted work, to the best of the authors’
knowledge.
Authors Shridevi Singh, MD, and Swapna Munnangi, PhD, had
full access
to all the data in this study and take responsibility for the
integrity of the
data and the accuracy of the data analysis. The data that support
the
findings of this study are available from the correspondi ng
author L.D.
George Angus, MD, upon reasonable request.
The authors declare no conflicts of interest.
5. (Aubron et al., 2012; Bliemel et al., 2017; Zielinski et al.,
2015). Elderly patients tend to be institutionalized with
lower mobility or have medical comorbidities such as hy-
pertension, diabetes, stroke, or dementia that predispose
these patients to bladder or bowel incontinence and UTI
(Foxman, 2014; Mody & Juthani-Mehta, 2014; Woodford
& George, 2009). In addition, less attention to sanitary
precautions further predisposes this specific patient pop-
ulation to high rates of UTIs (Alpay et al., 2018).
Although current guidelines do not recommend treat-
ing asymptomatic bacteriuria (Zalmanovici Trestioreanu,
Lador, Sauerbrun-Cutler, & Leibovici, 2015), this specific
population subset may not be able to vocalize or validate
symptoms due to altered mental status and communica-
tion incapability as a result of dementia, stroke, etc. (Tsu-
da et al., 2015). Hence, we presume that in this specific
patient population, UTI is a missed diagnosis because
of the missed clinical correlation needed as per current
UTI diagnostic criteria guidelines (CDC, 2019; Rowe &
Juthani-Mehta, 2014). Failure in early diagnosis and treat-
ment in this specific elderly patient population results in
morbid outcomes for patients and significant financial
penalties for institutions (Detweiler et al., 2015; Thakker
et al., 2018; Zielinski et al., 2014). However, the question
arises whether a CAUTI diagnosis is truly the progres-
sion of asymptomatic bacteriuria due to the indwelling
catheter or is rather a result of comorbid UTI at admis-
sion. Therefore, we propose that by screening geriatric
hip fracture patients with a urinalysis (UA) within 24 hr of
an indwelling urinary catheter that is placed at admission,
we will find there is a significant frequency of patients
who present with either UTI on admission or with UA
findings that could predispose patients to a UTI with an
indwelling urinary catheter.
6. METHODS
A retrospective observational study of patients at an ur-
ban Level I trauma center, as verified by the American
College of Surgeons, was performed. The trauma center is
a 500-bed public safety-net hospital that serves 1.4 million
people, with approximately 75,000 emergency depart-
ment visits and approximately 1,700 trauma admissions
each year.
After obtaining approval from the Institutional Review
Board (19-205), the trauma registry was queried by us-
ing ICD-10 codes S72.001-S72.26 for hip fracture for all
patients 65 years and older from January 1, 2017, through
December 31, 2018, which were the first 2 years that
routine screening UA was included as a component of
the multidisciplinary geriatric hip fracture comanagement
protocol at this institution (Wallace et al., 2019). Routine
screening UAs were obtained within 24 hr of admission.
Demographic information, comorbid conditions, prein-
jury medications, mechanism of injury, vital signs, Abbre-
viated Injury Score, Injury Severity Score, Revised Trau-
ma Score, Glasgow Coma Scale, admission disposition,
hospital course, intensive care unit (ICU) length of stay,
hospital length of stay, complications, disposition, and
outcome were extracted from the trauma registry supple-
mented by direct review of the electronic medical record.
Initially, 193 patient records were identified. However, 10
of these patient records were deemed incomplete and
were excluded, as they either did not have at least one of
the above data points available or the screening UA per-
formed, leaving 183 patients for the final sample. There
was no historical control group, as the frequency of UTI
and asymptomatic bacteriuria at the time of admission
were the variables of interest. All patients were admitted
to the ICU as part of our institution's protocol for geriatric
hip fracture patients.
8. The diagnosis of UTI in this study was made based on
the following UA results regardless of clinical symptoms:
white blood cells >10/high-power field (hpf), +nitrites,
+bacteria. Comparisons of outcomes were then com-
pared to subgroups within the data collected. Patients di -
agnosed with UTI were treated with antibiotics.
Statistical Analysis
Descriptive statistics were used to summarize the demo-
graphic and clinical variables in the study sample. Con-
tinuous variables were summarized by presenting mean
and standard deviation. Categorical variables were sum-
marized using frequency and percentages. The study
sample was stratified into two groups based on whether
or not the patient had a UTI upon admission. Continu-
ous variables were compared using unpaired Student's
t-test. The Fisher exact test or Pearson χ2 test was used
to examine the association of categorical variables with
UTI on admission. A p value < .05 was considered sta-
tistically significant. Statistical analysis was performed
using SAS version 9.4 (SAS Institute, Cary, NC).
RESULTS
The study sample consisted of 183 hip fracture patients
who met the inclusion criteria. Of these 183 patients,
36.07% had a UTI on admission, and 63.93% did not.
Table 1 depicts the baseline clinical and demographic
characteristics of the study sample stratified by the UTI
TABLE 1 Demographic and Clinical Characteristics
Variable
Total Sample
9. (n = 183)
n (%)
UTI on Admission
(n = 66; 36.07%)
n (%)
No UTI on Admission
(n = 117; 63.93%)
n (%) p Value
Age, M (SD), year 84.9 (8.0) 86.2 (7.5) 84.2 (8.3) .108
Sex
Female 140 (76.5) 53 (80.3) 87 (74.4) .363
Male 43 (23.5) 13 (19.7) 30 (25.6)
Mechanism of injury .715
Fall from bed 5 (2.7) 1 (1.5) 4 (3.4)
Fall from chair 10 (5.5) 3 (4.5) 7 (6.0)
Fall from stairs 19 (10.4) 7 (10.6) 12 (10.3)
Fall from toilet 2 (1.1) 2 (1.1) 1 (0.8)
Fall same level 141 (77.0) 50 (75.8) 91 (77.8)
Fall unspecified 2 (1.0) 1 (1.5) 1 (0.8)
Other 4 (2.2) 3 (4.5) 1 (0.8)
10. Mortality 8 (4.4) 4 (6.1) 4 (3.4) .401
ICU length of Stay, Mdn (IQR), day 3 (1.0) 3 (3.0) 2 (1.0) .004
Hospital length of stay, Mdn (IQR), day 4 (4.0) 5 (5.0) 4 (3.0)
.118
CAUTI 8 (4.4) 0 (0.0) 8 (6.8)
Foley days, Mdn (IQR), day 2 (1.0) 2 (1.0) 2 (1.0) .593
Injury Severity Score, M (SD) 9.9 (2.9) 10.2 (3.1) 9.7 (2.8)
.307
Glasgow Coma Scale, M (SD) 14.7 (1.2) 14.5 (1.6) 14.8 (.88)
.219
Hospital disposition .806
Acute rehabilitation 91 (49.7) 29 (43.9) 62 (53.0)
Died full code/withdrawal of care 8 (4.4) 4 (6.1) 4 (3.4)
Home 4 (2.2) 2 (3.0) 2 (1.7)
Skilled nursing facility 15 (8.2) 6 (9.1) 9 (7.7)
Subacute rehabilitation 61 (33.3) 24 (36.4) 37 (31.6)
Other nursing facility 4 (2.2) 1 (1.5) 3 (2.6)
Note. CAUTI = catheter-associated urinary tract infection; ICU
= intensive care unit; IQR = interquartile range; UTI = urinary
tract infection.
12. sample. The inhospital complications were not signifi-
cantly different between those who had a UTI on admis-
sion and those who did not.
DISCUSSION
The elimination of all CAUTI is not attainable; however,
it is necessary to take “reasonable preventive” measures
TABLE 2 Comorbidities
Comorbidity
Total Sample
(n = 183)
n (%)
UTI on Admission
(n = 66; 36.07%)
n (%)
No UTI on Admission
(n = 117; 63.93%)
n (%) p Value
Anticoagulation 48 (26.2) 20 (30.3) 28 (23.9) .347
Bleeding disorder 3 (1.6) 1 (1.5) 2 (1.7) .920
CHF 37 (20.2) 14 (21.2) 23 (19.7) .802
Chronic renal failure 15 (8.2) 5 (7.6) 10 (8.5) .217
Cirrhosis 2 (1.1) 0 (0.0) 2 (1.7) .536
15. CAUTI during their hospital course, and 66 of 183 (36%,
Table 1) patients had UTI on admission. The increased
incidence of CAUTI seen in previous studies compared
to our data supports the theory that the colonization of
urine with bacteria might have already been present and
untreated. It is generally recommended that patients with
asymptomatic bacteriuria should not be treated, and for
the nonelderly hip fracture patient, we agree. The limita-
tion in obtaining symptomatology history in this specific
patient population due to their comorbidities (e.g., de-
mentia) and the significant incidence of positive UA at
admission in this study supports the theory that the clini -
cal diagnosis of UTI should be assessed objectively and
thus treated appropriately in elderly hip fracture patients.
Study Limitations
The retrospective design of the study is a limitation in
itself. Our data were collected by analyzing medical re-
cords, which intrinsically lends itself to systematic bias.
The validity of data relating to such things as laboratory
values and interpretation can therefore not be fully guar-
anteed. Our sample size was also small, and we hope to
elaborate with future studies. However, as a pilot study,
we believe that publishing our findings will engage the
academic community and help determine future study
parameters. Furthermore, as a descriptive, observational
study, there are limitations as there are no control groups,
and interpretation of results is therefore theoretical.
CONCLUSIONS
Based on our findings, we strongly believe that if an ad-
mission UA was conducted for elderly hip fracture patients
and positive results were treated accordingly, there would
be a significant reduction in the diagnosis of CAUTI. An
indwelling urinary catheter is commonly placed in elderly
16. hip fracture patients, increasing their inherent risk for a
UTI based on catheter placement alone. This study has
also demonstrated the increased incidence of positive
UA as an additional theoretical risk factor for CAUTI in
these patients. Because of potential for serious complica-
tions, mortality, and financial burden on institutions, early
identification of urinary tract infection or asymptomatic
TABLE 3 Inhospital Complications
Complication
Total Sample
(n = 183)
n (%)
UTI on Admission
(n = 66; 36.07%)
n (%)
No UTI on Admission
(n = 117; 63.93%)
n (%) p Value
Cardiac arrest with CPR 2 (1.0) 1 (1.5) 1 (0.8) .464
Myocardial infarction 1 (0.5) 0 (0.0) 1 (0.8) .639
Unplanned intubation 4 (2.2) 2 (3.0) 2 (1.7) .322
Unplanned return to OR 4 (2.2) 0 (0.0) 4 (3.4) .164
Unplanned return to ICU 1 (0.5) 1 (1.5) 0 (0.0) .361
18. We thank the patients at Nassau University Medical Cent-
er for trusting us with their care. We also thank the staff
of the trauma department at Nassau University Medical
Center for their continued commitment to patient care.
KEY POINTS
• Catheter-associated urinary tract infections (CAUTIs) are a
well-known complication among the geriatric hip fracture
population.
• CAUTI has negative consequences for both the patient and
the institution and may be due to urinary tract infection
(UTI) present on admission.
• This study observed outcomes in geriatric hip fracture
patients who underwent routine UTI screening on admission.
• The results of this study suggest reduced rates of CAUTI
compared to previously published literature.
• The results suggest there may be a role in routine UTI
screening for geriatric hip fracture patients.
TABLE 4 Comorbidities With CAUTI But No UTI on
Admission
Comorbidity
CAUTI (n =8; 4.4%)
n (%)
No UTI on Admission Excluding
CAUTI (n = 109)
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Research Report
Introduction
Urinary tract infections (UTIs) cause significant morbidity
and mortality in older adults, accounting for an estimated
15.5% of hospitalizations and 6.2% of infectious disease–
related deaths in patients 65 years and older.1 Among insti-
tutionalized adults, UTIs are the most common type of
infection and account for one-third of all infections.1 Older
adults are at higher risk for UTI because of increasing inci -
dence of urinary incontinence and retention, use of urinary
catheters, vaginal atrophy in postmenopausal women, long-
term institutionalization, and reduced immune function.1,2
Prophylactic antibiotics are often utilized in older
adults with recurrent UTIs. A retrospective cohort study
evaluated more than 19 000 patients ≥65 years old with
recurrent UTI who received prophylaxis with either trim-
ethoprim, cephalexin, or nitrofurantoin.3 Prophylaxis was
associated with a reduction in the risk of UTIs and UTI-
related hospitalizations.3
Currently, there are no treatment guidelines for the pre-
vention of recurrent UTIs. A major concern with use of
prophylactic antibiotics is antimicrobial resistance and
other adverse effects, including Clostridioides difficile.1
Antimicrobial resistance in community-acquired urinary
organisms is increasing in the United States. In nursing
home settings, colonization with multidrug-resistant organ-
isms is common.1
29. Methenamine is a Food and Drug Administration (FDA)-
approved medication used for the prevention of UTIs in
persons 6 years and older.4 The recommended dosing of
886308AOPXXX10.1177/1060028019886308Annals of
PharmacotherapySnellings et al
research-article2019
1University of Colorado, Aurora, CO, USA
Corresponding Author:
Danielle R. Fixen, Department of Clinical Pharmacy, Skaggs
School
of Pharmacy and Pharmaceutical Sciences, University of
Colorado,
Anschutz Medical Campus Mail Stop C238, 12850 E Montview
Blvd,
Aurora, CO 80045, USA.
Email: [email protected]
Effectiveness of Methenamine for UTI
Prevention in Older Adults
Marina S. Snellings, PharmD1, Sunny A. Linnebur, PharmD1,
Scott M. Pearson, PharmD1, Jeff I. Wallace, MD, MPH/MSPH1,
Joseph J. Saseen, PharmD1, and Danielle R. Fixen, PharmD1
Abstract
Background: Methenamine is a drug used for the prevention of
lower urinary tract infections (UTIs). However, efficacy
has not been established in older adults or patients with varying
degrees of kidney function. Objective: To evaluate the
effectiveness of methenamine for the prevention of UTI in
adults 60 years and older. Methods: This was a retrospective,
pre-post, observational study. The study included primary care
patients 60 years and older who were taking methenamine
30. between January 1, 2015, and September 30, 2018. The pri mary
outcome was the time to first UTI after methenamine
initiation compared with the average time between UTIs in the
12 months prior to methenamine initiation. Results: Of
434 patients reviewed, 150 met inclusion criteria. The average
time to UTI was 3.3 months prior to methenamine initiation
compared with 5.5 months after methenamine initiation (P =
0.0004). There were 33 patients (22%) who did not have
a UTI after methenamine initiation. Also, 14 patients (9.3%)
had a calculated CrCl <30 mL/min at baseline. The average
time to UTI in these patients was 3.3 months prior to
methenamine initiation compared with 12.7 months after
initiation
(P < 0.0001). Conclusion and Relevance: Methenamine use was
associated with a longer time to UTI in older adults
with varying degrees of kidney function. The effectiveness of
methenamine appeared to be similar regardless of kidney
function, which is new evidence. Because of a lack of acquired
resistance, methenamine may be an effective option for UTI
prophylaxis in older adults.
Keywords
methenamine, urinary tract infections, geriatrics, renal
insufficiency
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360 Annals of Pharmacotherapy 54(4)
methenamine hippurate for UTI prophylaxis according to
FDA labeling is 1 g by mouth twice daily. Methenamine
31. acts via conversion of hexamine to formaldehyde in the
bladder, which in turn acts as a bacteriostatic agent.4 Unlike
other antimicrobials, acquired resistance has not been dem-
onstrated with methenamine use, making it an attractive
option for UTI prophylaxis.5 FDA labeling for methena-
mine states that use is contraindicated in patients with a cre-
atinine clearance (CrCl) less than 30 mL/min; therefore, the
safety and efficacy of methenamine in this population
remains largely unknown.4
Prior studies evaluating the efficacy of methenamine for
UTI prophylaxis were often small and/or had mixed results.6
Furthermore, efficacy of methenamine has not been studied
specifically in older adults with varying degrees of kidney
function. The objective of this study was to determine the
effectiveness of methenamine for the prevention of UTIs in
older adults.
Methods
Study Design and Setting
This was a retrospective, pre-post, observational study of
methenamine for UTI prevention in older adults receiving
primary care at University of Colorado Health (UCHealth).
UCHealth is an integrated health system across Colorado
with more than 900 primary care clinics utilizing the elec-
tronic health record (EHR) EPIC (Verona, WI). Patients
aged 60 to 89 years prescribed methenamine between
January 1, 2015, and September 30, 2018, were identified
through an EHR report. Manual verification of study crite-
ria was completed via EHR review. Patients had to be
actively prescribed methenamine during the study period,
but records were reviewed for the entire time the patient
was prescribed methenamine. The study protocol was
reviewed and determined to be exempt by the Colorado
32. Multiple Institutional Review Board.
Participants
Patients were included if they were 60 years and older,
were prescribed methenamine for UTI prophylaxis, and
received care in a UCHealth primary care clinic. Patients
were required to have documentation of recurrent UTI,
defined as 2 or more UTIs in the 12 months prior to methe-
namine initiation. In addition, participants had to be a
UCHealth patient for at least 12 months prior to methena-
mine initiation or have outside records available in the
EHR. Exclusion criteria included spinal cord or urological
structural abnormalities, immunocompromised state, use
of other antimicrobial agents for UTI prophylaxis, no
serum creatinine (SCr) in the EHR within 12 months of
methenamine initiation, or evidence that the patient was
not adherent to methenamine.
Outcomes
The primary outcome was time to first UTI after methena-
mine initiation compared with the time between UTIs in the
12 months prior to methenamine initiation. UTI was defined
as one of the following: (1) antibiotic prescription with an
associated International Classification of Diseases diagno-
sis code for UTI, (2) bacteriuria with >100 000 colony-
forming units (cfu)/mL plus either an antibiotic prescription
or urinary symptoms, or (3) emergency department visit or
hospitalization for UTI. Secondary outcomes included
effectiveness of methenamine in patients with CrCl <30
mL/min compared with CrCl ≥30 mL/min and adverse
effects associated with methenamine.
Data Collection and Analysis
33. Patients were identified from an EHR report, and demo-
graphic data, pertinent lab values, methenamine prescribing
information, and UTI data were collected and recorded
using Microsoft Excel. Number of UTIs in the 12 months
prior to methenamine initiation and time to first UTI after
methenamine initiation were determined. Time between
UTIs in the 12 months prior to methenamine initiation was
calculated by dividing 12 months by the number of UTIs
during that time period to determine an average. In patients
who did not have a UTI after initiation of methenamine,
time to UTI was measured from methenamine initiation
date to date of data collection. Other variables collected
during the EHR review included the following: methena-
mine index (date first prescribed) and discontinuation dates,
height, weight, SCr at index date and highest SCr while on
methenamine, methenamine dose, provider type for methe-
namine prescription, reason for discontinuation, adverse
effects, type of UTI (symptomatic or asymptomatic), bacte-
ria identified in urine culture, antibiotics used for treatment
of UTI, source of antibiotic prescription, use of antibiotics
for other indications, catheter use, and use of other medica-
tions that increase risk of UTI (eg, corticosteroids, sodium-
glucose cotransporter-2 inhibitors). The baseline and lowest
CrCl were manually calculated using the Cockroft-Gault
equation by using the SCr at initiation and highest SCr
while on methenamine.
As our data were normally distributed, a 2-tailed paired
t-test was used for the primary outcome, with a P value of
<0.05 considered statistically significant. Descriptive sta-
tistics were used for demographic and clinical data.
Proportions were used for nominal data.
Results
A total of 434 patients were screened, of whom 150 patients
34. were included (Figure 1). Baseline characteristics are sum-
marized in Table 1. The mean age was 77 years, and the
majority of patients were white and female. The mean CrCl
Snellings et al 361
at time of methenamine initiation was 54 mL/min.
Urologists (66.7%) were the most common prescriber of
methenamine, followed by primary care physicians
(16.7%). The majority of patients (88.7%) were prescribed
methenamine hippurate 1 g by mouth twice daily, with 1 g
by mouth once daily being the second most common dosing
at the time of methenamine initiation (10.7%). There were
25 patients (16.7%) who used antibiotics for other indica-
tions while taking methenamine, and 17 patients (11.3%)
were taking medications that increased risk for UTIs (eg,
corticosteroids). Urinary catheters were utilized in 26
patients (17.3%) prior to methenamine initiation.
Primary Outcome
The average time to recurrent UTI was 3.3 months prior to
methenamine initiation compared with 11.2 months after
methenamine initiation (P < 0.0001; Table 2). There were 33
patients (22%) who did not have a UTI after methena mine
initiation. Of the 117 patients who had a UTI after methena-
mine initiation, 98 (83.8%) were symptomatic, 6 (5.1%) were
asymptomatic, and in 13 (11.1%), it was unknown.
Escherichia coli was the most common bacteria on urine cul -
ture (47%), followed by Klebsiella pneumoniae (12.8%).
Secondary Outcomes
A total of 14 patients (9.3%) had a calculated CrCl <30
35. mL/min at baseline. The average time to UTI recurrence in
these patients was 3.3 months prior to methenamine initia-
tion compared with 12.7 months after initiation (P <
0.0001). Of the 136 patients with CrCl ≥30 mL/min, the
average time to UTI was 3.3 months prior to methenamine
initiation compared with 11 months after initiation (P <
0.0001; Table 2). Adverse events occurred in 16 patients
(10.7%) and led to discontinuation of methenamine in 15
of these patients. The most common adverse events
included gastrointestinal effects and dysuria (Table 3). Of
the 16 patients with adverse effects, 1 patient had CrCl
<30 mL/min.
Discussion
In this retrospective analysis, the use of methenamine for
UTI prophylaxis led to a significantly longer time to UTI
recurrence in older adults with varying degrees of kidney
function. Our results are consistent with prior studies that
have found benefit of using methenamine for UTI prophy-
laxis.5-8 Importantly, the effectiveness and tolerability of
methenamine appeared to be similar regardless of kidney
function. Therefore, the avoidance of methenamine pre-
scribing in patients with decreased kidney function because
of lack of data may not be justified.
Our study evaluated average time to UTI recurrence
before and after methenamine initiation, whereas previous
studies have mostly evaluated the reduction in incidence of
UTI or bacteriuria after initiation of methenamine. A review
of adults 58 years and older, using methenamine for UTI
prophylaxis, found a reduction in incidence of UTI or bac-
teriuria.7 A Cochrane systematic review that included 13
studies and a total of 2032 patients found that methenamine
was effective for UTI prophylaxis in patients without renal
tract abnormalities (symptomatic UTI: RR = 0.24, 95% CI
36. = 0.07 to 0.89; bacteriuria: relative risk (RR) = 0.56, 95%
CI = 0.37 to 0.83).6 Another analysis evaluated rates of
reinfection during a 6-month period of prophylaxis with
methenamine compared with infection rates in the 6 months
prior to methenamine in 52 older women with recurrent
434 pa�ents
screened
150 pa�ents
included
284 pa�ents excluded
• Unclear if ≥2 UTIs prior to methenamine
ini�a�on (n=104)
• Lack of informa�on in EHR (n=104)
• No SCr (n=21)
• Taking other an�bio�cs for prophylaxis (n=20)
• Documenta�on of methenamine non-
adherence (n=18)
• Immunocompromised (n= 13)
• Other (n=4)
Figure 1. Patient screening.
Abbreviations: EHR, electronic health record; SCr, serum
creatinine;
UTI, urinary tract infection.
Table 1. Baseline Characteristics at the Time of Methenamine
Initiation.
Characteristic Patients (n = 150)
Age: mean (years) ± SD 77 ± 8
37. Sex, n (%)
Female 133 (88.7)
Race, n (%)
White 142 (94.7)
CrCl, mean (mL/min) ± SD 54.3 ± 21
Catheter use, n (%) 26 (17.3)
Patients taking medications that increase
risk of UTI, n (%)
17 (11.3)
Methenamine dose, n (%)
1 g Twice daily 133 (88.7)
1 g Daily 16 (10.7)
500 mg Twice daily 1 (0.7)
Provider type for prescription, n (%)
Urologist 100 (66.7)
Primary care physician 25 (16.7)
Urogynecologist 15 (10)
Infectious disease 5 (3.3)
Inpatient provider 4 (2.7)
Oncologist 1 (0.7)
Abbreviations: CrCl, creatinine clearance; UTI, urinary tract
infection.
362 Annals of Pharmacotherapy 54(4)
UTI hospitalized in a long-term care facility.8 Patients were
categorized into 1 of 3 groups based on degree of inconti -
nence and immobility (normal, partial, or total). There was
a lower rate of total reinfection cases per person in each
group over the 6-month period of prophylaxis with methe-
namine compared with when not on treatment (normal
38. [0.45 vs 2.82], partial [0.58 vs 4.33], and total [0.29 vs
5.24]).8 Finally, a case series of 4 patients, 89 years or older,
with history of multidrug-resistant UTIs found that methe-
namine appeared to be safe and effective for prevention of
recurrent UTIs.5
Our study found that patients had a mean of 4.4 UTIs per
year prior to methenamine initiation. This is similar to pre-
vious studies evaluating effectiveness of other prophylactic
agents. A retrospective analysis of 82 renal transplant recip-
ients with recurrent UTI showed that prophylaxis with cran-
berry juice significantly reduced annual number of UTI
episodes from 3.6 ± 1.4 per year to 1.3 ± 1.3 per year (P <
0.001).9 Prophylaxis with l-methionine also significantly
reduced annual UTIs from 3.9 ± 1.8 per year to 2.0 ± 1.3
per year (P < 0.001).9 Another study of 252 postmeno-
pausal women with recurrent UTI randomized patients to
either trimethoprim-sulfamethoxazole or lactobacillus for
prophylaxis.10 The mean number of symptomatic UTIs in
the 12 months prior to initiation of prophylaxis was 7 in the
trimethoprim-sulfamethoxazole group and 6.8 in the lacto-
bacillus group compared with 2.9 (95% CI = 2.3 to 3.6) and
3.3 (95% CI = 2.7 to 4.0) during 12 months of prophylaxis,
respectively. Median time to first UTI was 6 months for
trimethoprim-sulfamethoxazole and 3 months for lactoba-
cillus.10 Our study found a longer mean time to first UTI of
11.2 months with methenamine prophylaxis.
Regardless of kidney function, patients in our study
tolerated methenamine treatment with minimal adverse
effects. Our data are consistent with previous studies that
have shown low rates of adverse events with use of methe-
namine with adequate kidney function, but the finding in
patients with a CrCl <30 mL/min is new.5-8 Other antibiot-
ics that are used for UTI prophylaxis (trimethoprim-sulfa-
39. methoxazole, nitrofurantoin, and cephalexin) often have
higher rates of adverse effects, drug-drug interactions, and
concern for antimicrobial resistance.9-12
FDA labeling for methenamine states that use is contrain-
dicated in patients with CrCl <30 mL/min because of lack of
data and potential for adverse effects, with no dosage adjust-
ments provided for patients with kidney dysfunction.4 Our
study included 14 patients (9.3%) with CrCl <30 mL/min.
Although overall numbers were small, we found that methe-
namine was effective in patients with CrCl <30 mL/min.
Only 1 of 14 patients (7%) with CrCl <30 mL/min had a
documented adverse event, compared with 15 of 136 patients
(11%) with higher levels of kidney function. Interestingly, 16
patients were prescribed a reduced dose of methenamine 1 g
by mouth daily, but only one had a CrCl <30 mL/min.
Despite FDA labeling stating that use is contraindicated in
renal impairment, our results suggest that methenamine was
safe and effective in persons with reduced renal function.
Future studies with a larger number of patients are needed to
determine true efficacy and safety of methenamine in patients
with moderate to severe kidney dysfunction.
Our study has several advantages. In contrast to other
published studies, we used a pre-post study design, where
patients served as their own controls to assess effectiveness
of methenamine for UTI prophylaxis. We also collected
data on other potential confounders that could increase risk
of UTI, including catheter use and use of other medications
(eg, corticosteroids) known to cause UTI. In addition, our
study categorized patients based on CrCl at the time of
methenamine initiation. Our study specifically evaluated
effectiveness in adults 60 years of age and older, which is a
population at high risk for recurrent UTIs as well as for
negative outcomes from antibiotic use.
40. Our study has some limitations. The observational nature
of the study with retrospective analysis and manual EHR
review may have introduced bias. Determination of methena-
mine adherence, discontinuation, and adverse effects relied
on record review alone, which may have underreported these
measures. Determination of UTI relied on patients reporting
a UTI to a provider within the health system or having an
Table 2. Study Outcomes Based on Renal Function.
n (%)
Average Time to UTI Prior to
Methenamine Initiation (months)
Average Time to UTI After
Methenamine Initiation (months) P Value
All patients 150 (100) 3.3 11.2 <0.0001
CrCl <30 mL/min 14 (9.3) 3.3 12.7 <0.0001
CrCl ≥30 mL/min 136 (90.7) 3.3 11.0 <0.0001
Abbreviations: CrCl, creatinine clearance; UTI, urinary tract
infection.
Table 3. Adverse Events.
Adverse Event n (%)
Gastrointestinal effects 9 (56.3)
Dysuria 3 (18.8)
Hand/feet swelling 1 (6.3)
Insomnia 1 (6.3)
Fatigue 1 (6.3)
Elevated liver function tests 1 (6.3)
41. Snellings et al 363
office visit or emergency department visit where a UTI was
diagnosed. Additionally, some antibiotic prescriptions may
not have been captured if they were prescribed outside the
UCHealth system. Because this was a retrospective study, not
all patients had a UTI at the time of methenamine initiation,
which may have underestimated time to first UTI. In addi-
tion, there were 33 patients who did not have a UTI after
methenamine initiation. For these patients, time to first UTI
was measured from methenamine initiation date to date of
data collection, which likely underestimated time to first
UTI. Finally, asymptomatic bacteriuria was treated in several
patients, which may have overestimated the time to first UTI
after methenamine initiation.
Conclusion and Relevance
Our findings suggest that use of methenamine for UTI pro-
phylaxis in older adults was effective by significantly
extending time to UTI. This benefit was observed in patients
with normal and reduced kidney function, which is a new
finding. Clinicians should consider prescribing methena-
mine for UTI prophylaxis in older adults. Future prospec-
tive randomized controlled trials in patients with impaired
kidney function are needed to confirm efficacy and safety
of methenamine in this patient population.
Acknowledgments
The authors wish to thank the Health Data Compass Colorado
Center for Personalized Medicine for their help in creating a
data
report to identify eligible patients.
42. Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with
respect
to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research,
author-
ship, and/or publication of this article.
ORCID iD
Danielle R. Fixen https://orcid.org/0000-0002-7193-1756
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https://orcid.org/0000-0002-7193-1756
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290 WWW.JOURNALOFTRAUMANURSING.COM Volume 28
| Number 5 | September-October 2021
R E S E A R C H
INTRODUCTION
Geriatric hip fracture patients are susceptible to a high-
er rate of complications, with rates ranging from 7% to
40% (Bliemel et al., 2017; Różańska, Wałaszek, Wolak, &
Bulanda, 2016; Thakker et al., 2018). One such complica-
tion is catheter-associated urinary tract infection (CAUTI).
Risk factors inherent to this population include surgical
procedures, immobility, age, and the routine utilization of
indwelling urinary catheters in the perioperative period
(Detweiler, Mayers, & Fletcher, 2015; Hälleberg Nyman
et al., 2013; Zielinski et al., 2015). This complication
negatively impacts both the patient and the institution
providing care.
It is reported that 15.5% of hospitalized patients older
than 65 years have urinary tract infections (UTIs) (Centers
for Disease Control and Prevention [CDC], 2019; Foxman,
2010). Moreover, 6.2% of infectious disease-related deaths
are due to UTIs (Alpay, Aykin, Korkmaz, Gulduren, &
Caglan, 2018). Implementation of various measures has
led to a reduction in the incidence of UTIs; however, UTIs
are still prevalent, placing an enormous financial burden
on institutions (Polites et al., 2014; Rebmann & Greene,](https://image.slidesharecdn.com/copyright2021societyoftraumanurses-220921192542-52c74de9/85/Copyright-2021-Society-of-Trauma-Nurses-Unauthorized-reprod-1-320.jpg)
