Infección Aguda Aguda Del Tracto Urinario (Incluida La Pielonefritis) en Adultos - UpToDate

3/3/2019 Infección aguda aguda del tracto urinario (incluida la pielonefritis) en adultos - UpToDate
Autores: Thomas M Hooton, MD, Kalpana Gupta, MD, MPH

Editor de la sección: Stephen B Calderwood, MD
Editor Adjunto: Allyson Bloom, MD
Divulgaciones del contribuyente
Todos los temas se actualizan a medida que se dispone de nueva evidencia y se completa nuestro proceso de
revisión por pares .
Revisión de literatura vigente hasta: febrero 2019. | Este tema se actualizó por última vez el 20 de abril de
2018.
INTRODUCCIÓN
Las infecciones del tracto urinario (IU) incluyen cistitis (infección de la vejiga / tracto urinario
inferior ) y pielonefritis (infección del riñón / tracto urinario superior). La patogenia de la IU
comienza con la colonización del introito vaginal o el meato uretral por parte de los
uropatógenos de la flora fecal, seguida de la ascensión a través de la uretra hacia la vejiga. La
pielonefritis se desarrolla cuando los patógenos ascienden a los riñones a través de los
uréteres. La pielonefritis también puede ser causada por la siembra de los riñones por
bacteriemia. Es posible que algunos casos de pielonefritis estén asociados con la siembra de
los riñones a partir de bacterias en los linfáticos.
Este tema revisará el enfoque de los adultos con IU complicada aguda, que definimos como una
IU que posiblemente se haya extendido más allá de la vejiga (es decir, IU con fiebre u otros
síntomas sistémicos, pielonefritis sospechada o documentada, y IU con sepsis o bacteriemia).
En contraste, cuando hay síntomas de cistitis en ausencia de fiebre, dolor en el costado,
sensibilidad en el ángulo costovertebral y otros signos de enfermedad sistémica, consideramos
esta cistitis aguda simple. Este enfoque para categorizar la UTI ( tabla 1 ) difiere de otras
convenciones, como se explica en detalle a continuación.
Nuestros enfoques para el diagnóstico y el tratamiento de la cistitis aguda simple (es decir, los
síntomas de cistitis en ausencia de fiebre, dolor en el flanco, sensibilidad en el ángulo
costovertebral y otros signos de enfermedad sistémica) y las IU en poblaciones especiales se
analizan en otra parte:
● (Ver "Cistitis aguda simple en mujeres" .)

● (Ver "Cistitis aguda simple en hombres" .)
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● (Consulte "Infecciones del tracto urinario y bacteriuria asintomática en el embarazo" .)

● (Ver "Infección del tracto urinario asociada a catéter en adultos" .)
● (Ver "Infección del tracto urinario en receptores de trasplante renal" .)
● (See "Recurrent simple cystitis in women".)
Asymptomatic bacteriuria is also discussed in detail elsewhere. (See "Approach to the adult with
asymptomatic bacteriuria".)
UTI in children is also discussed separately.
TERMINOLOGY
We use the term acute complicated urinary tract infection (UTI) to refer to an acute UTI with any
of the following features, which suggest that the infection extends beyond the bladder (table 1):
• Fever (>99.9°F/37.7°C) – This temperature threshold is not well defined and should be
individualized, taking into account baseline temperature, other potential contributors to
an elevated temperature, and the risk of poor outcomes should empiric antimicrobial
therapy be inappropriate.
• Other signs or symptoms of systemic illness (including chills or rigors, significant fatigue
or malaise beyond baseline).
• Flank pain.
• Costovertebral angle tenderness.
• Pelvic or perineal pain in men, which can suggest accompanying prostatitis. (See
"Acute bacterial prostatitis" and "Chronic bacterial prostatitis".)
By this definition, pyelonephritis is a complicated UTI, regardless of patient characteristics. In the

absence of any of these symptoms, we consider patients with UTI to have acute simple cystitis
and manage the patient differently. (See "Acute simple cystitis in women" and "Acute simple
cystitis in men".)
We do not automatically consider patients with underlying urologic abnormalities (such as

nephrolithiasis, strictures, stents, or urinary diversions), immunocompromising conditions (such
as neutropenia or advanced HIV infection), or poorly controlled diabetes mellitus to have a
complicated UTI if they have no concerning symptoms for upper tract or systemic infection.
However, such patients can be at higher risk for more serious infection and have not traditionally
been included in studies evaluating the antibiotic regimens we typically use for acute simple
cystitis. Thus, we follow such patients more closely and/or have a low threshold to manage them
as complicated UTI (eg, if they have subtle signs or symptoms that could be suggestive of more
extensive infection). Many patients with significant urologic abnormalities come to clinical
attention for UTI because of signs or symptoms consistent with complicated UTI as defined here
(rather than features of simple cystitis alone).
We also do not automatically consider men to have acute complicated UTI in the absence of
concerning symptoms for upper tract or systemic infection. However, the possibility of prostatic
involvement should always be considered in men, and this is incorporated into our approach with
men with apparent simple cystitis. (See "Acute simple cystitis in men".)
Certain populations, such as pregnant women and renal transplant recipients, have unique
management considerations and thus are not included in the above categorization. These
populations are discussed elsewhere. (See "Urinary tract infections and asymptomatic
bacteriuria in pregnancy" and "Urinary tract infection in kidney transplant recipients".)
These definitions of acute simple cystitis and complicated UTI are different from other
categorizations, which themselves are somewhat variable. Specifically, cystitis or pyelonephritis
in a nonpregnant premenopausal woman without underlying urologic abnormalities has
traditionally been termed acute uncomplicated UTI [1], and complicated UTI has been defined,
for the purposes of treatment trials, as cystitis or pyelonephritis in a patient with underlying
urologic abnormalities. Individuals who do not fit into either category have often been treated as
having a complicated UTI by default. We favor an approach to treatment based on the extent of
infection and severity of illness. Since complicated UTI, as defined here, is a more serious
infection than simple cystitis, the efficacy of an antimicrobial agent is of greater importance, and
certain agents used for simple cystitis should not be used for complicated UTI because they do
not achieve adequate levels in tissue, which may be important for cure. Risk for infection with
drug-resistant organisms is a consideration in antibiotic selection for both simple cystitis and
acute complicated UTI.
MICROBIOLOGY
Escherichia coli is the most frequent cause of acute complicated urinary tract infections (UTIs).
Other uropathogens include other Enterobacteriaceae (such as Klebsiella spp and Proteus spp),
Pseudomonas, enterococci, and staphylococci (methicillin-sensitive Staphylococcus aureus
[MSSA] and methicillin-resistant S. aureus [MRSA]) [2,3]. The prevalence of particular
pathogens depends partially on the host. As examples, Pseudomonas is more common in
patients with health care exposures or instrumentation. Staphylococcus saprophyticus is an
occasional cause of pyelonephritis in young, otherwise healthy women. UTI due to Candida spp
is discussed in detail elsewhere. (See "Candida infections of the bladder and kidneys".)
Risk factors for UTI with resistant organisms include recent broad-spectrum antimicrobial use,
health care exposures, and travel to parts of the world where multidrug-resistant organisms are
prevalent [4-8] (table 2).
Increasing rates of resistance in uropathogens have been reported globally. As an example, in

the United States, one study documented a threefold increase in the prevalence of extended-
spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae among hospitalized patients

with UTIs from 2000 to 2009 [9]. In another study of patients with pyelonephritis presenting to
emergency departments across the United States, approximately 6 percent of the 453 E. coli
isolates produced ESBL, although rates varied by region and complicating features [10]. In
particular, a specific strain of E. coli, sequence type 131 (ST131), has emerged globally as a
major cause of fluoroquinolone-resistant and ESBL-producing E. coli urinary tract infections [11].
In one study of E. coli clinical isolates from extraintestinal sites, predominantly urine, collected at
Veterans Affairs (VA) laboratories across the United States, the ST131 clone accounted for the
majority of fluoroquinolone-resistant and ESBL isolates and was calculated to account for 28
percent of all VA E. coli isolates nationwide [12]. Carbapenem resistance among
Enterobacteriaceae has also increased. (See "Extended-spectrum beta-lactamases", section on
'Epidemiology' and "Overview of carbapenemase-producing gram-negative bacilli", section on
'Epidemiology'.)
CLINICAL MANIFESTATIONS
Typical presentation — The clinical spectrum of acute complicated urinary tract infection (UTI)
encompasses both cystitis with complicating features and pyelonephritis:
● Symptoms and signs of cystitis include dysuria, urinary frequency and urgency, suprapubic
pain, and hematuria. Patients with acute complicated UTI also have fever or other features
of systemic illness (including chills, rigors, or marked fatigue or malaise beyond baseline),
which suggest that infection has extended beyond the bladder.
● Symptoms and signs of pyelonephritis classically include fever, chills, flank pain,
costovertebral angle tenderness, and nausea/vomiting [13]. Symptoms of cystitis are often
but not universally present. Atypical symptoms have also been described, with some
patients complaining of pain in the epigastrium or lower abdomen.
For men, the clinical spectrum of UTI includes prostatitis, which should be considered in men
presenting with cystitis symptoms that are recurrent or are accompanied by pelvic or perineal
pain. (See "Acute bacterial prostatitis" and "Chronic bacterial prostatitis".)
Not all patients with acute complicated UTI present with clear symptoms localizing to the urinary
tract. As an example, patients with spinal cord injury and neurogenic bladder can present with
autonomic dysreflexia and increased spasticity. Elderly or debilitated patients may present with
more generalized signs or symptoms of infection (eg, fever and chills) without clear symptoms
localizing to the urinary tract.
Pyuria is present in almost all patients with UTI.
Complications — Patients with acute complicated UTI can also present with bacteremia,
sepsis, multiple organ system dysfunction, shock, and/or acute renal failure. This is more likely
to occur in patients with urinary tract obstruction, recent urinary tract instrumentation, or other
urinary tract abnormalities, and in patients who are elderly or have diabetes mellitus.
Acute pyelonephritis can also be complicated by progression of the upper urinary tract infection
to renal corticomedullary abscess, perinephric abscess, emphysematous pyelonephritis, or
papillary necrosis. Risk factors for such complications include urinary tract obstruction and
diabetes mellitus (particularly for emphysematous pyelonephritis and papillary necrosis). (See
"Renal and perinephric abscess" and "Emphysematous urinary tract infections".)
Xanthogranulomatous pyelonephritis is a rare variant of pyelonephritis in which there is massive

destruction of the kidney by granulomatous tissue. Most cases occur in the setting of obstruction
due to infected renal stones. Affected patients can present with weeks to months of insidious
and nonspecific signs and symptoms, such as malaise, fatigue, nausea, or abdominal pain. This
condition is discussed in detail elsewhere. (See "Xanthogranulomatous pyelonephritis".)
DIAGNOSTIC APPROACH
Evaluation — Acute complicated urinary tract infection (UTI) should be suspected in patients
with dysuria, urinary frequency or urgency, or suprapubic pain who also have fever, chills, flank
pain, pelvic or perineal pain (in men), or who otherwise appear clinically ill. Acute pyelonephritis,
specifically, should be suspected in patients presenting with fever and flank pain, even in the
absence of typical symptoms of cystitis. Acute complicated UTI is also often suspected in
patients with nonlocalizing fever or sepsis. Evaluation includes examination to assess for other
causes of illness and urine studies.
Physical exam should assess for costovertebral angle, abdominal, and suprapubic tenderness.
Among sexually active young women, a pelvic examination may be warranted, particularly if
symptoms are not convincing for a UTI, to evaluate for cervical motion or uterine tenderness,
which would be suggestive of pelvic inflammatory disease (see "Pelvic inflammatory disease:
Clinical manifestations and diagnosis", section on 'Evaluation'). Among men with symptoms of
pelvic or perineal pain, cautious digital rectal examination may be warranted to evaluate for a
tender or edematous prostate that would suggest acute prostatitis. (See "Acute bacterial
prostatitis".)
UTI is often suspected in elderly or debilitated patients who have nonspecific signs or symptoms,
such as falls, change in functional status, and change in mental status. However, growing
evidence indicates that these are not reliable predictors of bacteriuria or UTI [14-17]. When
these nonspecific signs or symptoms are accompanied by signs or symptoms of systemic
infection or pyelonephritis, evaluation for acute complicated UTI with urine studies, in addition to
a general infectious workup, is appropriate. (See "Diagnosis of delirium and confusional states",
section on 'Diagnostic tests'.)
For all patients with suspected acute complicated UTI, we send urine for both urinalysis (either
by microscopy or by dipstick) and culture with susceptibility testing. Urinalysis results inform the
diagnosis. Since pyuria is present in almost all patients with UTI; its absence suggests an
alternative diagnosis, particularly in patients who present with nonspecific symptoms. White cell
casts, in particular, suggest a renal origin for pyuria. However, pyuria and bacteriuria may
occasionally be absent if the infection does not communicate with the collecting system or if the
collecting system is obstructed. Growth of bacteria on urine culture also supports the diagnosis
of UTI, and susceptibility testing is essential to ensuring appropriate antimicrobial treatment. If
available, urine Gram stain can also be helpful to narrow down the list of potential causative
organisms and inform empiric antimicrobial selection. (See 'Management' below.)
Issues related to urine collection and testing as well as interpretation of urine culture colony
counts are found elsewhere. (See "Sampling and evaluation of voided urine in the diagnosis of
urinary tract infection in adults".)
Pregnancy testing is appropriate in women of childbearing potential when the possibility of

pregnancy cannot be reasonably excluded by history alone. Blood tests, such as general
chemistry and complete blood counts, are not generally necessary unless the patient is
hospitalized. Blood cultures are warranted for those who present with sepsis or severe illness.
Imaging — Most patients with acute complicated UTI do not warrant imaging studies for
diagnosis or management. Imaging is generally reserved for those who are severely ill, have
persistent clinical symptoms despite 48 to 72 hours of appropriate antimicrobial therapy, or have
suspected urinary tract obstruction (eg, if the renal function has declined below baseline or if
there is a precipitous decline in the urinary output). Imaging is also appropriate in patients who
have recurrent symptoms within a few weeks of treatment [18].
The main objective of imaging is to evaluate for a process that may delay response to therapy or
warrant intervention, such as a calculus or obstruction, or to diagnose a complication of infection,
such as a renal or perinephric abscess [18]. Imaging should be obtained urgently in patients with
sepsis or septic shock to identify any evidence of obstruction or abscess that requires urgent
source control.
Computed tomography (CT) scanning of the abdomen and pelvis (with and without contrast) is
generally the study of choice to detect anatomic or physiologic factors associated with acute
complicated UTI; it is more sensitive than excretory urography or renal ultrasound for detecting
renal abnormalities predisposing to or caused by infection and in delineating the extent of the
disease [19,20]. CT without contrast has become the standard radiographic study for
demonstrating calculi, gas-forming infections, hemorrhage, obstruction, and abscesses [20].
Contrast is needed to demonstrate alterations in renal perfusion. CT findings of pyelonephritis

include localized hypodense lesions due to ischemia induced by marked neutrophilic infiltration
and edema (image 1A-C) [19,21]. The CT can be normal in patients with mild infection [22].
Renal ultrasound is appropriate in patients for whom exposure to contrast or radiation is

undesirable [23]. Magnetic resonance imaging (MRI) is not advantageous over CT except when
avoidance of contrast dye or ionizing radiation is warranted [24]. (See "Pathogenesis, clinical
features, and diagnosis of contrast-induced nephropathy" and "Prevention of contrast
nephropathy associated with angiography".)
Resolution of radiographic hypodensities may lag behind clinical improvement by up to three

months [19,21,25].
Diagnosis — The diagnosis of acute complicated UTI is made in the following clinical scenarios:
● Symptoms of cystitis (dysuria, urinary urgency, and/or urinary frequency) along with fever
(>99.9ºF/37.7ºC) or other signs or symptoms of systemic illness, such as chills, rigors, or
acute mental status changes. In such cases, pyuria and bacteriuria support the diagnosis.
● Flank pain and/or costovertebral angle tenderness in the setting of pyuria and bacteriuria.
This is suggestive of pyelonephritis. Fever and typical symptoms of cystitis are usually
present, but their absence does not rule out the diagnosis. CT findings that support the
diagnosis include low attenuation extending to the renal capsule on contrast enhancement
with or without swelling and complications such as renal abscesses. However, a normal CT
does not rule out the possibility of mild pyelonephritis.
● Fever or sepsis without localizing symptoms in the setting of pyuria and bacteriuria may be
attributed to UTI if other causes have been ruled out. Careful clinical assessment is
necessary. The diagnosis of acute complicated UTI is unlikely if pyuria is absent.
The presence of bacteriuria (≥105 colony-forming units/mL of a uropathogen) with or without

pyuria in the absence of any symptom that could be attributable to a UTI is called asymptomatic
bacteriuria and generally does not warrant treatment in nonpregnant patients who are not
undergoing urologic surgery. (See "Approach to the adult with asymptomatic bacteriuria".)
The diagnosis of UTI in a patient with an indwelling urinary catheter is discussed in further detail
elsewhere. (See "Catheter-associated urinary tract infection in adults", section on 'Diagnosis'.)
The diagnosis of bacterial prostatitis in men, which can present with similar symptoms as
complicated UTI, is discussed separately. (See "Acute bacterial prostatitis", section on
'Diagnosis' and "Chronic bacterial prostatitis", section on 'Diagnosis'.)
MANAGEMENT
Empiric antimicrobial therapy should be initiated promptly, taking into account risk factors for
drug resistance, including previous antimicrobial use and results of recent urine cultures, with
subsequent adjustment guided by antimicrobial susceptibility data. Urology should be consulted
to address anatomic abnormalities if these are suspected or identified on imaging.
Approach to management of patients diagnosed with Candida urinary tract infections (UTIs) is
discussed elsewhere. (See "Candida infections of the bladder and kidneys", section on
'Treatment'.)
Indications for hospitalization — The decision to admit patients with acute complicated UTI
should be individualized. The decision to admit is usually clear when patients are septic or
otherwise critically ill. Otherwise, general indications for inpatient management include
persistently high fever (eg, >38.4°C/>101°F) or pain, marked debility, or inability to maintain oral
hydration or take oral medications. Additionally, inpatient management is warranted when urinary
tract obstruction is suspected or there are concerns regarding patient adherence.
Outpatient management is acceptable for patients with acute complicated UTI of mild to
moderate severity who can be stabilized, if necessary, with rehydration and antimicrobials in an
outpatient facility or the emergency department and discharged on oral antimicrobials with close
follow-up.
Many patients can be managed in the outpatient setting. As an example, in a study of 44

patients with pyelonephritis but no major comorbidities, a 12-hour observation period with
parenteral antimicrobial therapy in the emergency department followed by completion of
outpatient oral antimicrobials was effective management for 97 percent of patients [26].
Empiric antimicrobial therapy — The approach to empiric therapy of acute complicated UTI
depends on the severity of illness, the risk factors for resistant pathogens, and specific host
factors [1]. The choice among the options presented for each population depends on
susceptibility of prior urinary isolates, patient circumstances (such as allergy or expected
tolerability, history of prior antimicrobial use), local community resistance prevalence of
Enterobacteriaceae (if known), and drug toxicity, interactions, availability, and cost (algorithm 1
and algorithm 2).
Urine culture and susceptibility testing should be performed in all patients, and the initial empiric
regimen should be tailored appropriately to the susceptibility profile of the infecting pathogen,
once known [1]. (See 'Directed antimicrobial therapy' below.)
Data evaluating the efficacy of various regimens for acute complicated UTI are limited, and only
a small number of different regimens have been formally evaluated [27,28]. The
recommendations in this section are based instead on the expected microbial spectrum of
antimicrobial agents that achieve adequate urinary tract and systemic levels.
Critical illness and/or urinary tract obstruction — We use a broad-spectrum antimicrobial

regimen for empiric therapy of patients with acute complicated UTI who are critically ill (ie, with
sepsis or otherwise warranting intensive care unit admission), getting worse on current therapy,
or who have suspected urinary tract obstruction (eg, if the renal function has declined below
baseline or if there is a decline in urine output) (algorithm 1).
In such patients, we suggest an antipseudomonal carbapenem (imipenem 500 mg intravenously

[IV] every six hours, meropenem 1 gram IV every eight hours, or doripenem 500 mg IV every
eight hours) to cover extended-spectrum beta-lactamase (ESBL)-producing organisms and
Pseudomonas aeruginosa, as well as vancomycin to cover methicillin-resistant Staphylococcus
aureus (MRSA). Daptomycin and linezolid are alternatives to vancomycin.
Advanced cephalosporin or carbapenem combinations with beta-lactamase inhibitors (such as

ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam) also have
activity against some ESBL-producing and multidrug-resistant P. aeruginosa isolates and are
effective for acute complicated UTI [29-31], but because of cost and antimicrobial stewardship
concerns, they should only be used in select cases of highly resistant infections. If carbapenem
resistance is suspected based on prior susceptibility testing results, an infectious diseases
consult should be obtained. (See "Overview of carbapenemase-producing gram-negative bacilli",
section on 'Treatment'.)
The rationale for such broad coverage in these patients is the high risk of adverse outcomes
should empiric antimicrobial therapy be insufficient and the increasing prevalence of multidrug-
resistant organisms, even in the general population (see 'Microbiology' above). Patients who
have a UTI in the setting of urinary tract obstruction are at a particularly high risk of clinical
decompensation.
Such patients also warrant imaging to evaluate for obstruction or other complications that may
warrant intervention. (See 'Imaging' above.)
Results of urine culture and susceptibility testing should be followed to ensure that the chosen
empiric antimicrobial regimen is appropriate and to guide selection of definitive therapy. (See
'Directed antimicrobial therapy' below.)
Other hospitalized patients — For patients who are hospitalized for acute complicated UTI
(see 'Indications for hospitalization' above) but are not critically ill and do not have suspected
urinary tract obstruction, our approach to empiric antimicrobial regimen selection depends on the
risk for infection with multidrug-resistant gram-negative organisms (algorithm 1).
● No risk factors for infection with a multidrug-resistant gram-negative organism (table

2) – For these patients, we favor ceftriaxone (1 gram IV once daily) or piperacillin-
tazobactam (3.375 grams IV every six hours) for parenteral treatment because of their
safety profile and narrow spectrum compared with other parenteral agents. Oral or
parenteral fluoroquinolones (ciprofloxacin or levofloxacin) are also reasonable alternatives if

the patient has not had a urinary isolate resistant to fluoroquinolones in the prior three
months and the community prevalence of E. coli fluoroquinolone resistance is not known to
be higher than 10 percent.
Concern for particular pathogens should further inform the choice between these options. If
Enterococcus or Staphylococcus species are suspected (eg, because of prior urinary
isolates or gram-positive cocci on a current urine Gram stain), piperacillin-tazobactam is
preferred because it has activity against these organisms (if the patient cannot use
piperacillin-tazobactam because of allergies or otherwise, vancomycin plus one of the other
gram-negative agents can be used). If drug-resistant gram-positive organisms are
suspected because of previous urinary isolates or other risk factors, vancomycin (for MRSA)
or linezolid or daptomycin (for vancomycin-resistant Enterococcus [VRE]) should be added.
If there is a risk of P. aeruginosa (eg, because of prior urinary isolates or febrile
neutropenia), piperacillin-tazobactam at a higher dose (4.5 grams IV every eight hours) or a
fluoroquinolone should be chosen. Other antipseudomonal agents that can be used include
cefepime (2 grams IV every eight hours) and ceftazidime (2 grams IV every eight hours).
● At least one risk factor for infection with a multidrug-resistant gram-negative

organism (table 2) – For these patients, we favor empiric treatment with an
antipseudomonal carbapenem (imipenem 500 mg IV every six hours, meropenem 1 gram IV
every eight hours, or doripenem 500 mg IV every eight hours).
Concern for particular pathogens should further inform regimen selection. If Enterococcus
species or MRSA are suspected (eg, because of prior urinary isolates or gram-positive cocci
on a current urine Gram stain), we add vancomycin (for MRSA) or daptomycin or linezolid
(for vancomycin-resistant Enterococcus [VRE]).
Advanced cephalosporin or carbapenem combinations with beta-lactamase inhibitors (such

as ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam) also
have activity against some ESBL-producing and multidrug-resistant P. aeruginosa isolates
and are effective for acute complicated UTI [29-31], but because of cost and antimicrobial
stewardship concerns, they should only be used in select cases of highly resistant
infections. If carbapenem resistance is suspected based on prior susceptibility testing
results, an infectious diseases consult should be obtained. (See "Overview of
carbapenemase-producing gram-negative bacilli", section on 'Treatment'.)
empiric antimicrobial regimen is appropriate and to guide selection of definitive therapy. (See
'Directed antimicrobial therapy' below.)
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Outpatients — Patients with acute complicated UTI of mild to moderate severity who can
take oral medications reliably can be treated in the outpatient setting. The approach to selection
of an empiric outpatient antimicrobial regimen depends on the risk factors for infection with a
multidrug-resistant organism (in particular ESBL-producing isolates) (algorithm 2).
Recommended regimens are outlined below. (See 'Low risk of MDR infection' below and 'High
risk of MDR infection' below.)
Whether fluoroquinolones can be used (accounting for contraindications or concerns for

fluoroquinolone resistance specifically) is also an important consideration in regimen selection.
In the absence of resistance, fluoroquinolones provide a broad spectrum of antimicrobial activity
against most uropathogens (including P. aeruginosa), and achieve high levels in the urinary tract.
Studies of acute complicated UTI have shown that the fluoroquinolones are generally
comparable or superior to other broad-spectrum antimicrobials, including parenteral regimens
[27,32]. However, increasing rates of resistance to fluoroquinolones among uropathogens, even
among outpatients, are diminishing their value for this purpose [33]. (See "Acute simple cystitis
in women", section on 'Resistance trends in E. coli'.)
When a fluoroquinolone can be used, ciprofloxacin or levofloxacin are the most common agents.
Other less commonly used fluoroquinolones that are effective for UTIs include ofloxacin and
norfloxacin. Moxifloxacin attains lower urinary levels than other fluoroquinolones and should not
be used.
Although there are concerns about the potential adverse effects, including Clostridioides
(formerly Clostridium) difficile infection and ecological effects (ie, selection of resistant
organisms) of the fluoroquinolones, their benefits are thought to outweigh their risks for acute
complicated UTI.
Low risk of MDR infection — For outpatients with acute complicated UTI and no risk
factors for infection with a multidrug-resistant (MDR) gram-negative organism (table 2), empiric
antimicrobial regimen selection depends on contraindications to or other concerns with
fluoroquinolones (algorithm 2). These include allergy or intolerance to the fluoroquinolone class
(including prolonged QT interval or other risk factors for torsades de pointes) or an unmodifiable
drug interaction.
● Fluoroquinolone-based regimens – For patients who have no contraindications to

fluoroquinolone and are at low personal risk for a fluoroquinolone-resistant isolate (table 2),
we suggest an oral fluoroquinolone for empiric therapy. Appropriate regimens include
ciprofloxacin 500 mg twice daily, ciprofloxacin 1000 mg extended release once daily, or
levofloxacin 750 mg once daily [34-38]. Fluoroquinolones are given for five to seven days.
In the case that community prevalence of E. coli fluoroquinolone resistance is known to be

higher than 10 percent, we suggest a single dose of a long-acting parenteral agent prior to
administering the fluoroquinolone [39]. We prefer ceftriaxone (1 gram IV or intramuscular

[IM] once) because of its safety, efficacy, and microbial spectrum. Ertapenem (1 gram IV or
IM once) is an alternative for patients with an allergy that precludes ceftriaxone use or
expected resistance to ceftriaxone, and aminoglycosides (gentamicin or tobramycin 5 mg
per kg IV or IM once) are reserved for patients who cannot use the other two. Since timely
use of an agent with in vitro activity is essential to treat acute complicated UTI and minimize
progression of infection, the threshold for selecting an antimicrobial for empiric broad-
spectrum therapy should be set at a relatively low resistance prevalence. For
fluoroquinolones, a resistance prevalence of 10 percent has been suggested based on
expert opinion [1].
The benefits of fluoroquinolones are thought to outweigh their risks for acute complicated
UTI, but patients should be advised about the uncommon but potentially serious
musculoskeletal and neurologic adverse effects associated with fluoroquinolones. (See
"Fluoroquinolones", section on 'Adverse reactions'.)
● Fluoroquinolone-sparing regimens – For patients who have contraindications to

fluoroquinolones or other concerns about fluoroquinolone use, our approach depends on the
relative severity of illness. For those with mild infection, we use a single dose of a long-
acting parenteral agent followed by a non-fluoroquinolone oral agent [39].
As above, we prefer ceftriaxone (1 gram IV or IM once) as a long-acting parenteral agent

because of its safety, efficacy, and microbial spectrum. Ertapenem (1 gram IV or IM once) is
an alternative for patients with an allergy that precludes ceftriaxone use or expected
resistance to ceftriaxone, and aminoglycosides (gentamicin or tobramycin 5 mg per kg IV or
IM once) are reserved for patients who cannot use the other two.
Following the dose of the parenteral agent, options include the following:
• Trimethoprim-sulfamethoxazole – one double-strength (160 mg/800 mg) tablet orally

twice daily for 7 to 10 days
• Amoxicillin-clavulanate – 875 mg orally twice daily for 10 to 14 days
• Cefpodoxime – 200 mg orally twice daily for 10 to 14 days
• Cefdinir – 300 mg orally twice daily for 10 to 14 days
• Cefadroxil – 1 g orally twice daily for 10 to 14 days
For outpatients who are more ill or are at risk for more severe illness, continuing the
parenteral therapy pending culture results is reasonable.
empiric antimicrobial regimen is appropriate and to guide modification of the regimen, if
necessary. (See 'Directed antimicrobial therapy' below.)
High risk of MDR infection — For outpatients with acute complicated UTI and risk factors
for infection with a multidrug-resistant (MDR) gram-negative organism (table 2), we suggest
giving an initial dose of ertapenem 1 gram IV or IM (algorithm 2).
For patients who have no contraindications to fluoroquinolones (ie, allergy or expected

intolerability, including risk factors for torsades de pointes, or unmodifiable drug interaction) and
have not had fluoroquinolone use or a fluoroquinolone-resistant urinary isolate in the prior three
months, we follow this dose of ertapenem with a fluoroquinolone. Appropriate regimens include
ciprofloxacin 500 mg twice daily, ciprofloxacin 1000 mg extended release once daily, and
levofloxacin 750 mg once daily [34-38]. Fluoroquinolones are given for five to seven days. The
benefits of fluoroquinolones are thought to outweigh their risks for acute complicated UTI, but
patients should be advised about the uncommon but potentially serious musculoskeletal and
neurologic adverse effects associated with fluoroquinolones. (See "Fluoroquinolones", section
on 'Adverse reactions'.)
For patients who have either contraindications or concern for fluoroquinolone resistance, we
instead continue to administer ertapenem 1 gram IV or IM daily in the outpatient setting until
culture and susceptibility testing results return.
Once available, these results should guide selection of definitive therapy. (See 'Directed
antimicrobial therapy' below.)
Directed antimicrobial therapy — Results of urine culture and susceptibility testing should be
used to confirm that the chosen empiric regimen is active and to tailor the regimen, if
appropriate. In many cases, broad-spectrum empiric regimens can be replaced by a more
narrow-spectrum agent.
Patients who were initially treated with a parenteral regimen can be switched to an oral agent
once symptoms have improved, as long as culture and susceptibility testing allow. Appropriate
oral agents to treat acute complicated UTI include levofloxacin (750 mg once daily), ciprofloxacin
(500 mg twice daily or 1000 extended release once daily), and trimethoprim-sulfamethoxazole
(one double-strength [160 mg/800 mg] tablet orally twice daily) [34-36]. Oral beta-lactams are
less effective for acute complicated UTI but are appropriate alternatives if susceptibility is
documented and the other agents are not feasible. If Enterococcus is isolated, amoxicillin (500
mg orally every eight hours or 875 mg twice daily) is the agent of choice if the organism is
susceptible [40,41]. Use of nitrofurantoin, fosfomycin, and pivmecillinam should generally be
avoided in the setting of acute complicated UTI because they do not achieve adequate tissue
levels outside the bladder [1].
Occasionally, susceptibility results preclude the use of an oral regimen and a parenteral agent is
needed to complete the course of treatment. Options for outpatient administration of parenteral
antimicrobials include use of a peripherally inserted central catheter, a preexisting central

catheter, or IM injection.
Total duration of antimicrobial therapy generally ranges from 5 to 14 days, depending on the
rapidity of clinical response and the antimicrobial chosen to complete the course.
Fluoroquinolones are given for 5 to 7 days, trimethoprim-sulfamethoxazole for 7 to 10 days [42],
and beta-lactams for 10 to 14 days. Longer durations may be warranted in patients who have a
nidus of infection (such as a nonobstructing stone) that cannot be removed. The duration of
antimicrobial therapy need not be extended in the setting of bacteremia in the absence of other
complicating factors; there is no evidence that bacteremia portends a worse prognosis [43].
Several trials have indicated that five- or seven-day regimens of fluoroquinolones are
comparable to longer durations [35,44]. There are limited data evaluating the use of other oral
agents for acute complicated UTI [42,45,46].
Addressing underlying urinary tract abnormalities — In addition to antimicrobial therapy, the

possibility of urinary obstruction should be considered and managed, if identified. Patients who
have underlying anatomical or functional urinary tract abnormalities (including neurogenic
bladder, indwelling bladder catheters, nephrostomy tubes, urethral stents) may warrant
additional management, such as more frequent catheterization to improve urinary flow,
exchange or removal of a catheter, and/or urologic or gynecologic consultation. Antimicrobials
alone may not be successful unless such underlying conditions are corrected [47]. (See
"Catheter-associated urinary tract infection in adults", section on 'Catheter management'.)
Follow-up — Symptoms should improve promptly if antimicrobial therapy is effective. Among

patients treated as outpatients, those who had pyelonephritis should have close follow-up either
face-to-face or by telephone within 48 to 72 hours.
Any patients who have worsening symptoms following initiation of antimicrobials, persistent
symptoms after 48 to 72 hours of appropriate antimicrobial therapy, or recurrent symptoms within
a few weeks of treatment should have additional evaluation, including abdominal/pelvic imaging
(generally with computed tomography if not already performed) for factors that might be
compromising clinical response. Urine culture and susceptibility testing should be repeated, and
treatment should be tailored to the susceptibility profile of other causative organisms isolated.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Urinary tract infections in
adults".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer short,
easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Beyond the Basics topics (see "Patient education: Urinary tract infections in adolescents
and adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● We use the term acute complicated urinary tract infection (UTI) to refer to an acute UTI with
any features that suggest that the infection extends beyond the bladder (table 1). These
include fever (eg, >99.9°F/37.7°C), other signs or symptoms of systemic illness (including
chills, rigors, or altered mental status), flank pain, and costovertebral angle tenderness. By
this definition, pyelonephritis is a complicated UTI, regardless of patient characteristics. This
definition is distinct from traditional categorizations of UTI and is more focused on the
clinical presentation and severity of illness. (See 'Terminology' above.)
● Relevant uropathogens include primarily Escherichia coli, but also other

Enterobacteriaceae, other gram-negative bacilli (including Pseudomonas aeruginosa),
staphylococci, enterococci, and Candida species. Risk factors for resistant organisms
include recent broad-spectrum antimicrobial use, health care exposures, and travel to parts
of the world where multidrug-resistant organisms are prevalent (table 2). (See 'Microbiology'
above.)
● Acute complicated UTI should be suspected in patients with dysuria, urinary frequency or
urgency, or suprapubic pain who also have fever, chills, flank pain, or otherwise appear
clinically ill. Acute pyelonephritis, specifically, should be suspected in patients presenting
with fever and flank pain, even in the absence of typical symptoms of cystitis. In men, pelvic
or perineal pain accompanying urinary symptoms suggests prostatitis. UTI is also often
suspected in patients with pyuria and bacteriuria who have nonspecific signs of systemic
illness, such as lethargy or delirium, and in patients with nonlocalizing fever or sepsis. (See
'Clinical manifestations' above and 'Evaluation' above.)
● For patients with suspected acute complicated UTI, we send urine for both urinalysis (either
by microscopy or by dipstick) and culture with susceptibility testing. Imaging is generally
reserved for those who are severely ill, have suspected urinary tract obstruction, have
persistent symptoms despite 48 to 72 hours of appropriate antimicrobial therapy, or have
recurrent symptoms. (See 'Evaluation' above and 'Imaging' above.)
● The diagnosis of acute complicated UTI is made in patients who have consistent clinical
findings as well as pyuria and bacteriuria. UTI is unlikely if pyuria is absent. (See 'Diagnosis'
above.)
● Outpatient management is acceptable for patients with acute complicated UTI of mild to
moderate severity who can be stabilized, if necessary, with rehydration and antimicrobials in
an outpatient facility or the emergency department and discharged on oral antimicrobials
with close follow-up. (See 'Indications for hospitalization' above.)
● The approach to empiric therapy of acute complicated UTI depends on the severity of
illness, the risk factors for resistant pathogens, and specific host factors (algorithm 1 and
algorithm 2). (See 'Empiric antimicrobial therapy' above.)
• For patients who are critically ill or have urinary tract obstruction, we suggest an
antipseudomonal carbapenem plus vancomycin (Grade 2C). (See 'Critical illness
and/or urinary tract obstruction' above.)
• For other hospitalized patients, we suggest ceftriaxone or piperacillin-tazobactam if

there are no risk factors for a multidrug-resistant (MDR) gram-negative infection (table
2) (Grade 2C). Oral or parenteral fluoroquinolones are also reasonable options. For
such patients who have risk factors for an MDR gram-negative infection, we suggest an
antipseudomonal carbapenem (Grade 2C). (See 'Other hospitalized patients' above.)
• For outpatients without risk factors for an MDR gram-negative infection (table 2), we
suggest an oral fluoroquinolone, such as levofloxacin or ciprofloxacin (Grade 2B). If the
community prevalence of E. coli fluoroquinolone resistance is known to be higher than
10 percent, we also suggest a single dose of a long-acting parenteral agent prior to
administering the fluoroquinolone (Grade 2C). (See 'Low risk of MDR infection' above.)
• For outpatients with risk factors for an MDR gram-negative infection (table 2), we
suggest an initial dose of ertapenem (Grade 2C). Subsequently, an oral fluoroquinolone
or daily ertapenem can be used. (See 'High risk of MDR infection' above.)
● Results of urine culture and susceptibility testing should be used to confirm that the chosen
empiric regimen is active and to tailor the regimen, including switching a parenteral regimen
to an oral agent once symptoms have improved. Appropriate oral agents to treat acute
complicated UTI include fluoroquinolones (eg, levofloxacin or ciprofloxacin, given for 5 to 7
days) and trimethoprim-sulfamethoxazole (given for 7 to 10 days). Oral beta-lactams (given
for 10 to 14 days) are less effective for acute complicated UTI but are appropriate
alternatives if susceptibility is documented and the other agents are not feasible. (See
'Directed antimicrobial therapy' above.)
● Patients who have underlying anatomical or functional urinary tract abnormalities (including
neurogenic bladder, indwelling bladder catheters, nephrostomy tubes, urethral stents) may
warrant additional management, such as more frequent catheterization to improve urinary
flow, exchange or removal of a catheter, and/or urologic or gynecologic consultation. (See
'Addressing underlying urinary tract abnormalities' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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medical in-patients: A prospective cohort study. Arch Gerontol Geriatr 2017; 72:127.
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infection and complicated urinary tract infections: a systematic literature review of current
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29. Popejoy MW, Paterson DL, Cloutier D, et al. Efficacy of ceftolozane/tazobactam against
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30. Carmeli Y, Armstrong J, Laud PJ, et al. Ceftazidime-avibactam or best available therapy in
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31. Kaye KS, Bhowmick T, Metallidis S, et al. Effect of Meropenem-Vaborbactam vs

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33. Sanchez GV, Master RN, Karlowsky JA, Bordon JM. In vitro antimicrobial resistance of
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34. Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and
trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis
pyelonephritis in women: a randomized trial. JAMA 2000; 283:1583.
35. Peterson J, Kaul S, Khashab M, et al. A double-blind, randomized comparison of

levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for
10 days for the treatment of complicated urinary tract infections and acute pyelonephritis.
Urology 2008; 71:17.
36. Talan DA, Klimberg IW, Nicolle LE, et al. Once daily, extended release ciprofloxacin for
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171:734.
37. Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in
women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-
controlled, non-inferiority trial. Lancet 2012; 380:484.
38. Vellinga A, Tansey S, Hanahoe B, et al. Trimethoprim and ciprofloxacin resistance and
prescribing in urinary tract infection associated with Escherichia coli: a multilevel model. J
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39. Sanchez M, Collvinent B, Miró O, et al. Short-term effectiveness of ceftriaxone single dose
in the initial treatment of acute uncomplicated pyelonephritis in women. A randomised
controlled trial. Emerg Med J 2002; 19:19.
40. Shah KJ, Cherabuddi K, Shultz J, et al. Ampicillin for the treatment of complicated urinary
tract infections caused by vancomycin-resistant Enterococcus spp (VRE): a single-center
university hospital experience. Int J Antimicrob Agents 2018; 51:57.
41. Cole KA, Kenney RM, Perri MB, et al. Outcomes of Aminopenicillin Therapy for
Vancomycin-Resistant Enterococcal Urinary Tract Infections. Antimicrob Agents
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42. Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med 2012;
366:1028.
43. Mombelli G, Pezzoli R, Pinoja-Lutz G, et al. Oral vs intravenous ciprofloxacin in the initial
empirical management of severe pyelonephritis or complicated urinary tract infections: a
prospective randomized clinical trial. Arch Intern Med 1999; 159:53.
44. van Nieuwkoop C, van der Starre WE, Stalenhoef JE, et al. Duración del tratamiento de la
infección del tracto urinario febril: un ensayo pragmático, aleatorizado, doble ciego,
controlado con placebo, de no inferioridad en hombres y mujeres. BMC Med 2017; 15:70.
45. Warren JW, Abrutyn E, Hebel JR, et al. Pautas para el tratamiento antimicrobiano de la
cistitis bacteriana aguda no complicada y la pielonefritis aguda en mujeres. Sociedad de
Enfermedades Infecciosas de América (IDSA). Clin Infect Dis 1999; 29: 745.
46. Cronberg S, Banke S, Bergman B, et al. Menos recaídas bacterianas después del
tratamiento oral con norfloxacina que con ceftibuten en la pielonefritis aguda inicialmente
tratada con cefuroxima intravenosa. Scand J Infect Dis 2001; 33: 339.
47. Nicolle LE. Una guía práctica para el manejo de infecciones complicadas del tracto
urinario. Drogas 1997; 53: 583.
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3/3/2019 Infección aguda aguda del tracto urinario (incluida la pielonefritis) en adultos - UpToDate

Autores: Thomas M Hooton, MD, Kalpana Gupta, MD, MPH

Divulgaciones del contribuyente

● (Ver "Cistitis aguda simple en mujeres" .)

● (Consulte "Infecciones del tracto urinario y bacteriuria asintomática en el embarazo" .)

UTI in children is also discussed separately.

By this definition, pyelonephritis is a complicated UTI, regardless of patient characteristics. In the

We do not automatically consider patients with underlying urologic abnormalities (such as

Increasing rates of resistance in uropathogens have been reported globally. As an example, in

spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae among hospitalized patients

Pyuria is present in almost all patients with UTI.

Xanthogranulomatous pyelonephritis is a rare variant of pyelonephritis in which there is massive

Pregnancy testing is appropriate in women of childbearing potential when the possibility of

Contrast is needed to demonstrate alterations in renal perfusion. CT findings of pyelonephritis

Renal ultrasound is appropriate in patients for whom exposure to contrast or radiation is

Resolution of radiographic hypodensities may lag behind clinical improvement by up to three

The presence of bacteriuria (≥105 colony-forming units/mL of a uropathogen) with or without

Many patients can be managed in the outpatient setting. As an example, in a study of 44

Critical illness and/or urinary tract obstruction — We use a broad-spectrum antimicrobial

In such patients, we suggest an antipseudomonal carbapenem (imipenem 500 mg intravenously

Advanced cephalosporin or carbapenem combinations with beta-lactamase inhibitors (such as

● No risk factors for infection with a multidrug-resistant gram-negative organism (table

parenteral fluoroquinolones (ciprofloxacin or levofloxacin) are also reasonable alternatives if

● At least one risk factor for infection with a multidrug-resistant gram-negative

Advanced cephalosporin or carbapenem combinations with beta-lactamase inhibitors (such

Whether fluoroquinolones can be used (accounting for contraindications or concerns for

● Fluoroquinolone-based regimens – For patients who have no contraindications to

In the case that community prevalence of E. coli fluoroquinolone resistance is known to be

administering the fluoroquinolone [39]. We prefer ceftriaxone (1 gram IV or intramuscular

● Fluoroquinolone-sparing regimens – For patients who have contraindications to

As above, we prefer ceftriaxone (1 gram IV or IM once) as a long-acting parenteral agent

• Trimethoprim-sulfamethoxazole – one double-strength (160 mg/800 mg) tablet orally

For patients who have no contraindications to fluoroquinolones (ie, allergy or expected

antimicrobials include use of a peripherally inserted central catheter, a preexisting central

Addressing underlying urinary tract abnormalities — In addition to antimicrobial therapy, the

Follow-up — Symptoms should improve promptly if antimicrobial therapy is effective. Among

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

● Relevant uropathogens include primarily Escherichia coli, but also other

• For other hospitalized patients, we suggest ceftriaxone or piperacillin-tazobactam if

Use of UpToDate is subject to the Subscription and License Agreement.

3. Nicolle LE. A practical guide to antimicrobial management of complicated urinary tract

4. Khawcharoenporn T, Vasoo S, Singh K. Urinary Tract Infections due to Multidrug-Resistant

6. Walker E, Lyman A, Gupta K, et al. Clinical Management of an Increasing Threat:

infection. Eur J Clin Microbiol Infect Dis 2012; 31:423.

15. Dasgupta M, Brymer C, Elsayed S. Treatment of asymptomatic UTI in older delirious

21. Tsugaya M, Hirao N, Sakagami H, et al. Computerized tomography in acute pyelonephritis:

28. Golan Y. Empiric therapy for hospital-acquired, Gram-negative complicated intra-abdominal

31. Kaye KS, Bhowmick T, Metallidis S, et al. Effect of Meropenem-Vaborbactam vs

35. Peterson J, Kaul S, Khashab M, et al. A double-blind, randomized comparison of

Tema 16109 Versión 44.0

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