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Urinary tract infection in patients

with diabetes mellitus
Vladimir Tesar

Vnitr ní lékar ství

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 ClinicalNephrology,Vol.77 - No. 1/2012(40-48)

in patients
tractinfection
Urinary withdiabetes
mellitus
ReinhardFünfstück1, MarkolfHanefeld3
LindsayE. Nicolle2, and KurtG. Nabera

Ww&ryxmw&
l Departmentof lnternal Medicine, Sophien-und Hufeland-KlinikumWeimar,
@2012Dustri-VerlagDr. K. Feistle
tssN 0301-0430
Germany,2Universityof Manitobaand Health SciencesCentre, Winnipeg,
Manitoba,Canada,3Centerfor clinical studies,GWT, TechnicalUniversityDresden,
DOt10.5414/CN107216
e-pub:December20. 2011 and aTechnicalUniversityof Munich, Depaftmentof Urology,Munich, Germany

Key words Abstract. Urinary tract infection occurs
diabetesmellitus- with increasedfrequencyand severity in pa-
urinarytract infection- tients with diabetes mellitus. General host
pyelonephritis - anti-
factors enhancingrisk for urinary tract infec-
biotics
tion in diabeticsinclude age, metabolic con-
trol, and long term complications,primarily
diabetic nephropathy and cystopathy.Altera-
tions in the innate immune systemhave been
described and may also contribute. Treat-
ment of asymptomaticbacteriuriain diabetic
patientsis not indicated.Early diagnosisand
prompt interventionis recommendedto limit
morbidity of symptomatic infection. Clini-
cal studies comparing managementof uri-
nary tract infection in personswith diabetes
comparedto thosewithout aswell as diabetic
patients with good or poor glucose control
will be necessaryto improve care of urinary
infection in personswith diabetesmellitus.
Introduction
Clinical observations suggest an asso-
ciation between diabetes mellitus and an
increased susceptibility to and severity of
infections [1]. Metabolic abnormalities and
long term complications including neuropa-
,thy and nephropathyare presumedto be de-
terminäntsof increasedinfectious morbidity
l2l,but the specific contributionsof individ-
ual variables are not well characterized.In
Received addition, the heterogeneityof diabetic popu-
March10.2011: lations compromises efforts to understandt
accepted
June 7 , 2011 the associations of diabetes mellitus and
infection. Urinary tract infection is one of
Correspondence to the most common infections. It occurs with
Prof.Dr. Reinhard
increasedfrequency and severity in diabetic
Fünfstück
Sophien-und Hufeland- populations, and is more likely to be asso-
KlinikumWeimar, ciated with complications [3]. This review
Henry-van-de-Velde- summarizesthe current understandingof this
Straße2,99425
important infection in diabetic patients.
Weimar,Germany
innerel@ Urinary tract infection may present as
klinikum-weimar.de asymptomatic bacteriuria, acute uncompli-
cated urinary tract infection in women (acute
cystitis or acutenonobstructivepyelonephri-
tis), complicated urinary tract infection in
men or women with underlying abnormali-
ties of the genitourinary tract and, in men,
acute or chronic bacterial prostatitis. Infec-
tion is often recurrent,either as relapsewhen
an organismpersistswithin the genitourinary
tract and recurs following treatment, or rein-
fection with new organismsintroduced into
the genitourinary tract.
Epidemiology
Asymptomaticbacteriuriaoccursin 8 - 26%
of diabeticwomeq a prevalenceestimatedto be
2 - 3 times higherthan nondiabeticwomen [4].
There is limited, if any, increasedfrequency of
asymptomaticbacteriuria for diabetic men.
In a cohortof over 6,000patientswith dia-
betes mellitus enrolled into ten clinical trials
of diabetestherapies,the incidence of urinary
infection was 91.5/1,000 person-yearsfor
women and 28.211,000for men; the cumula-
tive risk over 6 months was 3.5oÄof women
and 1.IoÄ of men [5]. In the Dutch National
Survey of GeneralPractice,patientswith Type
1 diabetesmellitus were 1.96times more like-
ly to experienceurinary infection (95oÄ con-
fidence intervals (CD 1.49 - 2.58), and with
Type 2 diabetes1.24 times more likely (95%
CI 1.10- 1.39) t6l. A casecontrol study of
pre-menopausalwomen enrolled in a Wash-
ington health group reporteddiabeteswas an
independent risk factor for pyelonephritis,
with an oddsratio of 4.1 (95% CI 1.6- 10.9)
[7]. Women 30 years or older with diabetes
enrolled from ten Dutch primary care praa-
tices experiencedrelapse and reinfection in
7.1% and 15.90Ä,respectively,compared
Urinarytract infectionin patientswith diabetesmellitus 41

urea level> 300 mmol/l sluco$e level > 10 rnmolll

c)4
r
o)
o
(E
g
o
Cz

s a m p l e s of urine

r-I E. coli ATCC 25922

f-fl E.coliDsM787
Figure1. Growthof E.coliin urinewith high glucoseor high urea concentrations [16].Growthratesof
E.coliAtrCC25922 (Americantype culturecollection;Rocheville,USA and E.coliDSM 7871 Germancol-
lectionof microorganismsand cell cultures;Braunschweig,Germany)were analyzed.Strainswere incu-
batedon MacConkeyagarat 37 'C. One colonyformingunitof eachstrainwas suspendedin 2 ml of both
sterilized
urinesamples,dilutedto an concentrationof 106cfu/ml,and incubatedat 37 "C for t h. Cultures
werethen dilutedwith sterileurineto 103cfu/mlatO,2 5 and 8 h. A 100 pl and 50 pl aliquotof thesesus-
pensionswas inoculated onto MacConkeyagarplates.Plateswere incubatedat 37'C for 1B h and colo-
nies were counted.

with 2.AoÄ and 4.1oÄ for women without Pathogenesis

diabetes [8]. In a Canadianreport, diabetic
women were 6 - 15 times more frequently
hospitalizedfor acutepyelonephritisand dia-
beticmen 3.4 - 17 times [9], while a Danish
study reporteddiabeticswere 3.0 times more
likely to be hospitalized with urinary tract
infection1101.
A retrospective analysis of patients en-
rolled in two clinical trials of urinary tract in-
fection found that diabetesmellitus was one
of four variables independently associated
with a poor outcome(clinical or bacteriologi-
cal failure or relapse)of therapy for acutepy-
s R 8 .3;95%C 12.3- 30.3)[11].
e l o n e p h ri ti(O
Other evidence supporting increasedsever-
ity of infection is an increased frequenc$
of bacteremia,more prolonged duration of
fever, and increasedmortality (12.5% with
diabetesand 2.5oÄwithout) in older patients
with diabetes[12]. Over 90% of episodesof
emphysematouspyelonephritis cases occur
inpersonswith diabetes[13] and6TYoof epi-
sodesof emphysematous cystitis [14]. Thus,
the evidencesupportingan excessburden of
urinary infection in personswith diabetesis
compelling.
Hostdefense
tlrinary tract infection occurs when bac-
teria or fungi colonizing the urethra and, in
women, the vagina ascend into the bladder
and kidney. Normal host defense mecha-
nisms usually prevent entry to or persistence
of bacteriawithin the urinary tract.
Urine is a good nutrient source for most
microorganisms.The growth rate of bacteria
and fungi in urine is stimulated by glycos-
uria [5]. Figure 1 demonstratesthe growth
kinetics of E. coli corcelatedwith urinary
glucoselevel in diabetic patientswith an in-
creasedHbAlc-level. The clinical scenario
where hyperglycosuriahasthe most immedi-
ate relevanceis in presentationsof emphyse-
matouscystitis or pyelonephritis,where high
urine glucose levels provide a substratefor
Enterobacteriaceaein the urine resultins in
gasformation[13,14].
Bacterial attachment to the uroepithe-
lium is the necessaryinitiating event permit-
ting bacterialpersistence,and also stimulates
early activation of the innate immune system.
Fünfstück,Nicolle,Hanefeldand Naber
Typel fimbriated (fimH) E. coli strainsare the
predominantphenotypic variant isolated from
patients with urinary tract infection, and the
presenceof this adhesinis essentialfor estab-
lishing acute cystitis. Geerlings and Hoepel-
mann [16] demonstratedthat E. coll express-
ing Type 1 fimbriae have increasedadherence
to uroepithelial cells of women with diabetes
mellitus comparedto thosewithout diabetes.
Urittuty Tamm Horsfall glycoprotein (TT{P)
incorporates high-mannose and NeuAccr2,
3Gal sequenceswhich are ligands for both
Type 1 and Type S fimbriatedE. coli. Pak et al.
[7] showedthat THP binds typel fimbriated
E. coli in vitro and thus preventsE. coli from
attaching to the membrane glycofroteins of
the luminal surface of the uroepithelial cells
(Uroplakin Ia and Ib). A reduction of urinary
THP excretion which correlates with reduc-
tion of renal massis consistentlyobservedin
diabetic nephropathy [8, 19]. Glycation of
THP in patients with diabetesor renal diseas-
es also reducesthe capacityof THP to inhibit
bacterial adherenceto human uroepithelium
[20]. However, the clinical relevanceof uri-
nary THP excretion or glycation on urinary
infection has not yet been described.
Local urinary cytokinesregulatehost de-
fence against urinary tract infections. Acti-
vation of Toll-like receptorson uroepithelial
cells promotesreleaseof cytokineswhich, in
turn, recruit and activate granulocytes, mac-
rophages,monocytes and other immune reg-
ulatory cells [21]. A potential risk factor for
urinary tract infection is polymorphonuclear
leukocyte dysfunction in a high-glucose state
122, 231. Studies of neutrophil function in
diabetic patients, however, report contradic-
tory resultsl24,25l, andthe incidenceof uri-
nary tract infection is not increased in other
groups of patients with neutrophil defects or
neutropenia 1261.Signifi cantly lower urinary
IL-8- and Il-6-concentrations are found in
diabetic women comparedwith nondiabetic
controls, and these lower levels correlate
with lower urinary leukocyte counts 1271.On
the other hand, Zozulinska et aI. [28] found
increasedbaselinelevels of IL-8 in serum of
patientswith diabetes.Li etaI.l29l observed
that advanced glycation end products found
in serum of diabetic subjects may inhibit the
enzymatic and bactericidal activity of lyso-
zymq blocking bacterial agglutination and
impairing killing activity of lactoferrin. Both
42
actions are important in the flrst line of de-
fense against urinary tract infection. Thus,
studiesdescribea number of alternationsof
the innate immune system in patients with
diabetes,although the clinical relevance of
thesealterationsremainsuncertain.
Diabetes complications
General host factors associatedwith risk
of infection in patients with diabetesinclude
age, metabolic control, duration of diabe-
tes mellitus, microvascular complications,
urinary incontinence, and cerebrovascular
diseaseor dementia [30]. While the specific
variables contributing to the increased inci-
denceand severity ofurinary tract infection in
diabetic patientsremain poorly characteized,
most studiesreport that diabetic patients with
long term complications are at greaterrisk [1,
2,3l.However in the Epidemiologyof Dia-
betes Interventions and Complications study
[31], the only risk factor associatedwith acute
cystitis in premenopausalwomen with Type
I diabeteswas sexual activity, similar to non-
diabetic women. This highlights the difficul-
ties in generalizationgiven the heterogenicity
of populationswith diabetesmellitus.
Over 50% of men and women with diabe-
teshavebladderdysfunctionwhich may impair
voiding and facilitate infection 132,331. The
presenceofrenal diseaseis an additional pre-
dictor of urinary tract infection [34]. Urinary
incontinence is consistently associatedwith
urinary tract infection in diabetic women [35,
36], but this associationis not likely causative.
Diabetic cystopathy is an insidious problem
attributable to autonomic nervous dysfunc-
tion and characJeizedby a loss of sensation
of bladder distension leading to decreased
frequency of voiding and increasedpost-void
residualurine volume. Bladder dysfunctionoc-
6 curs in 26 - 86% of diabeticwomen depending
on age, extent of neuropathy and duration of
diabeticdisease[33]. The possibility that void-
ing disordersare contributing to UTI should be
consideredin all diabeticpatients.
Mi crobioIogicaI aspecfs
The most common uropathogen isolated
from symptomatic or asymptomaticinfection
Urinarytract infectionin patientswith diabetesmellitus
is E. coli. Other bacteia, suchasProteusspp.,
Klebsiella spp.,Enterobacterspp. andEntero-
coccusspp. areisolatedlessfrequently 14,16].
Bacteria which cause acute, uncomplicated
urinary infection in normal women express
virulence determinantswhich maybe found on
chromosomalor extrachromosomalgenes.For
uropathogenic E. coli, these virulence factors
include an affay of toxins such as hemolysin,
iron scavengingsystemssuch as hydroxamate/
aerobactin,ffid adhesinssuch as mannose-re-
sistant or mannose-sensitivehemagglutins or
specific O- or K-antigens [37]. E. coli isolated
from the urine of diabetic patientswith asymp-
tomatic bacteriuria have a low frequency of ge-
notypic virulence characteristics, dn observa-
tion consistentwith nondiabeticpatients with
asymptomatic bacteriuria or complicated uri-
nary infection [15, 38, 39]. For instance,genes
determining production of hemolysins and
colony necrotizing factor 1, typical virulence
properties associatedwith acute symptomatic
episodes of urinary tract infection, are less
frequent [37]. Meiland et al. [a0] also report-
ed fimH genetic sequencesof E. coli strains
isolated from asymptomatic bacteriuria were
similar for diabetic and non-diabetic women,
although they did not describe strains isolated
from symptomaticepisodes.
Hospital basedmicrobiology surveysfrom
Italy [41] and Greece la2l reported no differ-
ences in bacterial spectrum or susceptibility
of organisms isolated from the urine of dia-
betic or nondiabetic patients. Colodner et al.
143], however, described a higher frequency
of extendedspectrumbeta-lactamase(ESBL)
producing E. coli andKlebsiella pneumoniae
in non- hospitalizedIsraeli diabetic compared
with non diabetic patients. Similar results
were forind by Rodriguez-Bano et al. pal in
Spanish patients with community acquired
ESBL urinary infection. However, neither
study reported whether diabetes was an in-
dependentrisk factor for increasedresistance*
once age, prior antimicrobial treatment, or
urologic abnormalitieswere considered.
Diagnosis
Clinical
Diabetic patients generally present with
symptoms similar to nondiabetic patients.
43
These are frequency,urgency, dysuria, or su-
prapubic discomfort for lower tract infection,
and costovertebralangle pain or tenderness,
often with fever, for upper tract infection.
Clinical signsmay be alteredin somepatients
with peripheral or autonomic neuropathy.Pa-
tients with diabetes are more likely to have
more severe presentationsof pyelonephritis
including feveq bacteremia, andbllateral renal
involvement 112].Less frequentpresentations
of urinary infection which occur most often
in patients with diabetes include emphyse-
matous cystitis or pyelonephritis, ureteral ob-
struction secondaryto papillary necrosis,and
renal or perinephric abscesses.Rarely, acute
renal failure complicating pyelonephritis has
been reported, and most casesdescribed are
patientswith diabetes.
Symptomatic urinary tract infection in
diabetes mellitus may be complicated by
hypo- or hyperglycemia, hyperosmolar de-
hydration, or ketoacidosiswhich may further
impair the host responseto infection. Early
diagnosis and treatment of symptomatic in-
fection and metabolic abnormalities is im-
portant to limit morbidity.
Laboratory
A urine specimen for culture should be
obtained prior to initiating antimicrobial
therapy for every diabetic patient present-
ing with pyelonephritis or complicated uri-
nary tract infection. Women with symptoms
consistent with acute cystitis and who do
not have diabetic nephropathy or other long
term complications, particularly if they have
a prior history of recurrent acute cystitis, do
not usually require a urine culture. However,
thesewomen should also have a urine speci-
men for culture if this is a recurrent episode
within one month of treatment, if empiric
therapy has failed, or if there has been recent
antimicrobial treatment so resistant organ-
isms are more likely.
A diagnosisof bacteriuria is made when
> 105cfu/ml of an organismis isolated from
a voided urine specimen.For diabetic wom-
en with good metabolic control and without
long term complications who present with
acute uncomplicated cystitis, quantitative
counts < 10s cfu/ml are isolated from 20 to
25oÄ of premenopausalwomen and about
Fünfstück.Nicolle.Hanefeldand Naber
l0oÄ of postmenopausalwomen. OnIy 5%
of patients with acute pyelonephritis have
lower quantitative counts isolated. Isolation
of lower quantitative counts is presumed
to result from impaired renal concentrating
ability or diuresiswhich limits the dwell time
of urine in the bladder.
Pyuria is a universal accompanimentof
symptornatic urinary tract infection. It is
also presentin 70oÄof diabetic women with
asymptomatic bacteriuria [4]. Pyria may
also be causedby vaginal, bladder or renal
conditions other than urinary tract infection.
Thus, the presenceof pyuria,by itself, is not
useful for diagnosis of urinary tract infection
or to differentiate asymptomatic änd symp-
tomatic infection. The absence of pyuria,
however, is useful to exclude urinary tract
infection in patients with questionablesymp-
toms.
Diagnosticimaging
The increasedfrequencyof seriouscom-
plications of urinary tract infection in pa-
tients with diabetesrequires a low threshold
for obtaining diagnostic imaging 13, 451.
Diabetic patients who present with severe
systemic manifestationsof disease,includ-
ing severe sepsis or septic shock, all men,
patients who do not respondfollowing 48 -
72 h of appropriate antimicrobial therapy, or
who experience early symptomatic relapse
following discontinuation of antimicrobial
therapy should have diagnostic imaging per-
formed promptly to identi$r underlying ab-
normalities which may require intervention.
- Ultrasound and intravenous urography
were pieviously the most common imaging
studies used. Ultrasound scanning is safer,
less costly, and easier to perform. These
methods allowed detection of calculi, ob-
struction, and incomplete bladder emptying.
Computerized tomography (CT) is now ac-
ceptedas the most sensitiveimaging modal-
ity for diagnosis and follow-up of abnor-
malities potentially associatedwith urinary
tract infections [46]. An enhancedCT scanis
preferred,but contrastmedia should be used
with caution in patients with diabetes mel-
litus or with renal disease,given the risk for
contrast media induced renal failure. It has
been recommendedthat metformin be dis-
44
continued on the day of contrast in1'ectionif
the glomerular filtration rate (GFR) is < 60
mUmin/1.73m2, and restartedtwo days later,
providing the GFR has not significantly dete-
riorated [47]. Nuclear medicine has a limited
role in the evaluation of urinary infections in
adults, and is used primarily for the assess-
ment of renal function. Magnetic resonance
imaging (MRI) has a limited but increasing
role. It is particularly useful for patients with
allergy to iodinatedcontrastmedia,but is not
as reliable as a CT scanfor identifuing gas or
stonesin the genitourinary tract.
Treatmentstrategies
Treatment of urinary tract infection in
patients with diabetes is generally similar
to non-diabetic patients [48]. Key factors
to consider include whether the patient is
asymptomatic or symptomatic, whether in-
fection is localized to the bladder or kidney,
and renal function. For diabetic patients,the
severity of metabolic alterations character-
ized by hyper- or hypoglycemia, increas-
ing signs of insulin resistance,the level of
HbAlc, and glycosuria must also be consid-
ered.
Asymptomatic bacteriuria
There are no short or long term beneflts
for treatment of asymptomatic bacteriuria in
women with diabetesmellitusl49,50l. Treat-
ment of asymptomaticbacteriuria in stabledi-
abetic patients does not reduce the frequency
of subsequentsymptomatic episodesof cysti-
tis or pyelonephritis or hospitalization for uri-
nary tract infection. Asymptomatic bacteriuria
by itself is not associatedwith an increased
rate of progression to renal impairment or
other long term complicationsin patientswith
diabetes [50]. Thus, screening for and treat-
ment of asymptomatic bacteriuria in diabetic
patientsis not indicated[51].
Symptomaticinfection
Acute cystiti'sin women with good glucqse
control and without long term complications
should be managedas uncomplicatedurinary
 Urinarytract infectionin patientswith diabetesmellitus 45

improved, and urine culture results are avall-

Table1. Recommendations for antimicrobial therapyin uncomplicated
cysti-
tis in patientswith diabetesmellitus[48, 52, 53]. able. If infection is associatedwith complica-
tions such as renal or perinephric abscessesor
Antimicrobial Regifien Duration
emphysematouspyelonephritis,prompt inter-
Firstline
Fosfomycintrometamol 3 , 0 0 0m g sinqledose
vention with a combined surgical and medical
Nitrofurantoin 5 0 - ' 1 0 0 m g o r a l l y3 - 4 t i m e sa d a y 5 days approachis often required.
Nitrofurantoin 100 mg twicea day 5 days
monohydrate/
macrocrystals
TMP-SMX- 800/160mg orallyevery12h 3 days Antimicrobial seIection
Trimethoprim 200 mg every12 h 5 days
Alternatives The choice of initial empiric antimicrobi-
Ciorofloxacin 250 - 500 mg orallyevery 12 h 3 days al therapy should considercurrent treatment
Levofloxacin 250 - 500 mg every 12 h 3 days guidelines, the patient's metabolic status
Norfloxacin 400 mg orallyevery'12h 3 days and tolerance,the clinical presentation,and
Ofloxacin 200 mg orallyevery12 h 3 days known or suspectedlocal or institutional sus-
Cephelexin 500 mg 4 timesdaily 7 days
ceptibility of uropathogens(Tables1,2) 13,
Cefuroximeaxetil 500 mg twicedaily 7 days
52, 531.Broad spectrumcephalosporinsand
Cefpodoximeproxetil 100 mg orallyevery12 h 3 days
400 mg daily
fluoroquinolonesare the drugs of choice for
Cefixime
pyelonephritis.However, alternateregimens
*trimethoprim/sulfamethoxazole. such as the carbapenems- meropenem,er-
tapenem or doripenem - or beta lactamlbeta
lactamase inhibitors such as piperacillin/
therapyfor uncomplicatedpy-
Table2. Preferredregimensfor antimicrobial tazobactam or ampicillin/sulbactam may be
withdiabetesmellitus[52,53].
elonephritis
appropriate if antimicrobial resistanceis a
Antimicrobial Reqimen concern. For patients who present with se-
Intravenousadministration vere sepsisor septic shock, broad spectrum
Cefotaxime 1 gq B h antimicrobial therapy to provide maximal
Ceftriaxone 1-2qdaily
coverage for resistant organisms should be
Ciorofloxacin 400 mg twicea day
initiated pending urine culture results.
Levofloxacin 500 - 750 mg oncea day
Gentamicin or tobramvcin
with 3- 5mg/kgonceaday Possibledrug interactionsbetweenantimi-
ampicillin 2glVq6h crobials and antidiabetic or antihypertensive
Oral administration drugs must be considered(Table 3). Antimi-
Levofloxacin 250 - 500 mq once a dav crobials may impair glucose homeostasisand
Ciprofloxacin 500 mg twice a day lipid metabolism[54, 55]. Antimicrobialswith
Cefpodoximeproxetil 200 mg twice a day
nephrotoxicsideeffects,e.g. aminoglycosides,
Amoxicillin/clavullanic
acid 1 1 0 . 2 - 2 1 0 . 2 93 t i m e sa d a y
should be used with caution in patients with
TMP.SMX- 160i800mg twicea day
renal insufficiency. Patients with diminished
*if isolatesusceptible. renal function are also susceptibleto the neph-
rotoxic effects of drug combinations such as
cephalosporinsgiven with furosemideor ethac-
infection,usually with shortterm antimicrobial rynic acid. Someantibioticscauseelevationof
therapy(Tablel) 152,531.Patientswith pyelo- the serumcreatinineby mechanismsotherthan
nephritis and mild or moderately severepre- nephrotoxicity.For instance,trimethoprim can
sentationscan usually be successfullytreated inhibit tubular secretionof creatinine.Tetracy-
with oral therapy(Table2) 152,531.However, cline has an antianaboliceffect in renal failure
patientswith pyelonephritisand severesystem- and is best avoided, but doxycycline may be
ic symptomsincluding nauseaand vomiting or used if there is a clear indication, such as ure-
hemodynamic instability should be hospital- thritis. Nitrofurantoin should be avoided in re-
ized for initial parenteral antibiotic therapy. nal failure as drug metabolitesaccumulateand
Patients with gastric emptying impairment may causeperipheral neuropathy [56]. While
will also usually require parenteral therapy. no other antimicrobialsare specificallycontra-
Parenteralantimicrobialtherapyis modified to indicatedin renal insufficiency,dosageadjust-
an oral regimen once patientscan tolerateoral ments appropriateto the level of renal impair-
therapy, the clinical status of the patient has ment are usually necessary.
Fünfstück,
Nicolle,Hanefeldand Naber 46

Table3. Potentialmetabolicside effectsof antimicrobial

drugson glucoselevelin diabeticpatients.

Antimicrobial sustances Effectson glucose levr

substances Effects on glucose level Antimicrobial
l :l:..11l:.:ri:il::::ll
Ciproloxacin t Ampicillin 1
Levofloxacin t Amoxicillin J
Gatifloxacin ft Sulbactam/ 1J
Norfloxacin none ampicillin
Aminoglycosides Tazobactam none
Gentamicin none
Tobramycin none Cefazolin none
Amikacin none Cefuroxime none
Contrimoxazole Cefotaxime none
Nitrofurantoin nOnö',r' Ceftazidime J
none Cefixime none
Oätbiä,penems
lmipenem none
Meropenem none
Ertapenem none

Recurrentinfection in patientswith diabetesmellitus. Symptom-

atic infection is associatedwith an increased
The management of recurrent urinary severity and frequency of complications.
tract infection is similar for diabetic and non- The underlying mechanismsdeterminingthe
diabeticpatients.Recurrentinfection in young increasedrisk and severity of infection are
women without long term complications of not fully described,but alterationsin specific
diabetesis managedas acute uncomplicated componentsof the host response,metabolic
cystitis, including antimicrobial therapy giv- abnormalities,and long term complications
en as long term low dose or post intercourse of diabeteslikely all contribute. The hetero-
prophylaxis for women with very frequent re- genicity of diabetic populations complicates
culrences[53]. Managementof recurrentin- efforts to identifli specific determinants of
fection in individuals with complex urologic increasedmorbidity. To better define man-
abnormalities or renal failure is more prob- agementstrategiesand prognosis,diagnostic
lematic. For patientswith complicatedinfec- evaluation and therapeutic outcome should
tion prophylactic antimicrobial therapy is not be stratified by age, sex, the site of urinary
recommendedas this does not decreasethe tract infection, underlying renal or bladder
frequency of symptomaticurinary tract infec- impairment, and the metabolic status of the
tion and leadsto recurrentinfection with more patient. Controlled clinical trials of therapy
resistantorganisms.It is essentialto identi$r comparing patients with and without diabe-
and correct any known urologic abnormali- tes mellitus, or diabetic patients stratifledby
ties and to optimize voiding, including use of adequacyof control and complications will
intermittent catheterizationwhere appropri- be necessaryto improve managementof this
ate. For some patients with renal impairment common and important problem.
or men with prostate infection, bacteria may
persist within the nonfunctioning kidney or
prostate despite prolonged courses of anti- i
microbial therapy. In selected patients with
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l2l McMahon MM, Bistrian BR. Host defenses and
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