Beruflich Dokumente
Kultur Dokumente
Pyelonephritis in Pregnancy
An Update on Treatment Options for Optimal Outcomes
Jennifer A. Jolley and Deborah A. Wing
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of California,
Irvine, Orange, California, USA
Contents
Abstract 1643
1. Acute Pyelonephritis in Pregnancy 1643
2. Complications of Acute Pyelonephritis in Pregnancy 1645
3. Conventional Therapy 1646
4. Antimicrobial Resistance; A Growing Public Health Concern 1648
4.1 Antimicrobial-Resistant Uropathogens in Antepartum Pyeionephritis 1650
5. Rationaie tor Hospitalization ot Pregnant Patients with Pyelonephritis 1650
6. Ambuiatory Treatment ot Acute Pyelonephritis 1650
6.1 Nonpregnant Patients 1650
6.2 Pregnant Patients 1651
6.3 Recommendations tor Ambuiatory Treatment of Pyelonephritis in Pregnancy 1652
7. Conclusions 1653
Abstract Acute pyelonephritis is one of the most common indications for ante-
partum hospitalization. When acute pyelonephritis is diagnosed, conven-
tional treatment includes intravenous fluid and parenteral antibacterial
I administration. There are litnited data by which to assess the superiority of
; one antibacterial regimen over the other in terms of efficacy, patient accep-
tance and safety for the developing fetus; however, it is important to consider
antimicrobial resistance patterns in the local community when choosing an
agent. Moreover, there are growing public health concerns regarding anti-
microbial resistance to commonly prescribed medications for urinary tract
infections in pregnancy. There is a small body of evidence to support the
ambulatory treatment of pregnant women with pyelonephritis in the first and
early second trimesters, but the majority of women will be managed as in-
patients. This article provides a suggested algorithm for the treatment of
pyelonephritis during pregnancy.
colony-forming units (cfu) of a uropathogen,''] Clinical signs and symptoms of acute pyelo-
have a 20- to 30-fold increased risk of deve- nephritis include fever, shaking chills, flank pain,
loping pyelonephritis in pregnancy compared nausea and vomiting, costovertebral angle ten-
with women without bacteriuria.'-] In addition, derness (CVAT) and, less commonly, symptoms
treatment of ASB in pregnancy decreases the risk of cystitis such as dysuria and increased fre-
of subsequent pyelonephritis from approximately quency.'*' Urinary dipstick testing for the pre-
20-35% to 1-4%.'-''] Pyelonephritis in pregnancy sence of leukocyte esterase and nitrites may be
occurs mostly prior to delivery, with 10-20% positive.'"'^] The diagnosis is confirmed by urine
of cases diagnosed in the first trimester'''-^] and culture, obtained usually by midstream clean-
the majority of cases occurring in the second and catch, but occasionally by suprapubic aspiration
third trimesters. Pyelonephritis can also occur or urethral catheterization. To obtain a proper
postpartum.'*] clean-catch specimen, the patient should be in-
Numerous physiological changes predispose structed to wipe her introitus from front to back
the pregnant woman to urinary tract infection prior to micturition in order to avoid contamina-
(UTI). Ureteral and renal calyceal dilatation are tion with periurethral bacteria. According to the
evident as early as 12 weeks' gestation, thought Infectious Diseases Society of America (IDSA)
to be due to progesterone-induced relaxation. consensus definition of pyelonephritis, colony
Ureteral peristalsis slows and the enlarging uterus counts of >100 000 cfu/mL from clean-catch voided
compresses the ureters, particularly on the right specimens are acceptable for use in antimicrobial
side. Mechanical compression of the bladder and treatment studies, and provide a sensitivity of
decreased detrusor tone lead to increased capa- 90-95%.1'-^] One or two bacteria per high-power
city and incomplete emptying of the bladder. All field on an unspun catheterized urine specimen.
of these factors contribute to ureteral dilatation or more than 20 bacteria per high-power field
and urinary stasis. Increases in glomerular filtra- on spun urine, closely correlates with > 100 000 cfu/
tion with resultant elevations in urinary glucose mL bacteria on urine culture.''''] Pyuria or the
levels and alkalization of urine also facilitate presence of leukocyte casts are also consistent
bacterial growth. with the diagnosis.
Women with urinary tract anomalies such Uropathogens responsible for pyelonephritis
as incompetent vesicourethral valves and renal are taxonomically the same as those that cause
calculi, medical conditions including diabetes ASB and cystitis. The most common uropatho-
mellitus, sickle cell disease or trait, and neuro- gen is Escherichia coli, which is cultured from
logical problems such as paralysis from spinal 70-85% of patients.'''''] Other Gram-negative uro-
cord injury, are at increased risk for acquiring pathogens include Klebsiella, Enterohacter and
pyelonephritis in pregnancy. Pyelonephritis is Proteus spp. A contemporary cohort study'''!
also more likely to occur in women of low socio- noted far fewer infections caused by Klebsiellu
economic status.'^'**] In a retrospective review or Enterobacter species (3%) than the 23% of cases
of 242 nonpregnant women aged 18^9 years reported historically.'^] Gram-positive organisms
with pyelonephritis, other risk factors for the dis- that are frequently identified include Enlerococcus
ease included frequency of sexual intercourse in faecalis and group B streptococci. Gram-positive
the previous 30 days, recent spermicide use, re- microbes are found more commonly as pregnancy
cent UTI and recent incontinence.'^] The over- progresses.''']
lap of these risk factors with those described
The pathogenesis of ASB and risk factors
for women with cystitis supports the view that
for progression to symptomatic UTI, including
pyelonephritis usually involves ascent of infect-
pyelonephritis, are incompletely understood. A
ing microbes from the bladder.'^' Another study
complex interplay between virulence factors of
noted that low expression of an interleukin re-
uropathogenic bacterial species, such as E. coli
ceptor may confer a familial susceptibility to
and Proteus mirabilis, and host defence mech-
pyelonephritis.''"]
anisms likely dictates the severity of UTIs in
2010 Adis Data Information BV. AN rights reserved. Drugs 2010; 70(13)
Treatment of Pyelonephritis in Pregnancy 1645
women. For example, E. coli from a small group 391 patients with pyelonephritis in pregnancy,
of 0-serotypes have characteristics epidemiolo- only 6% of patients required changes in antibac-
gically associated with acute pyelonephritis, chro- terial therapy, most commonly for persistent
nic or recurrent infection, parenchymal scarring fever and not correlated with urine or blood cul-
and renal failure in the normal urinary tract.''^' ture results.'^^' A change in management because
The main reservoir for E. coli causing UTI is the of bacteraemia alone occurred in only 1% of
intestinal tract, but only a small proportion of cases.'''^' The limited utility of routine cultures in
E. coli bacteria that inhabit the intestines actually the clinical management of patients suggested
cause UTI. Factors that enhance the adherence of that patient care would not be compromised in
E. coli to uroepithelial cells and thereby protect their absence. Some authors recommend obtain-
the bacteria from urinary lavage and increase ing blood cultures only if the patient has a high
their ability to multiply and invade renal tissue temperature, e.g. >39C, appears to have sepsis or
have been identified. These include adhesins such has a major co-morbidity such as adult respira-
as P-fimbria and S-fimbria,'"'"'''' and haemolysin tory distress syndrome (ARDS).'''--''^^^'
production.'-"' Adhesins can bind erythrocyte When acute pyelonephritis during pregnancy
membranes and inhibit serum bactericidal activ- is diagnosed and treated in a timely fashion, the
ity by expression of genes associated with ampi- outcome for both mother and fetus is generally
cillin resistance.'-^'' The class of Dr adhesins has good. However, there are serious complications
been associated with pyelonephritis in pregnancy that can arise. The aim of this article is to provide
and a high rate of preterm delivery in mice.'-'"''' an overview of the diagnosis, possible compli-
Individual genetic factors may also be associated cations, and management options for women
with human bladder immune responses prior to with pyelonephritis during pregnancy. This guide
the development of symptomatic UTIs.'^'*' Contrib- serves as an update of a 2001 article detailing
utors to the uropathogenic potential of F. mirabilis treatment options for optimal outcomes.'''^' Al-
include fimbriae and urease production.'-''' though the management of the disease has not
In addition to urinalysis and urine culture, changed appreciably over the last 10 years, the
laboratory evaluation often includes a complete disturbing trend of antibacterial resistance has
blood cell count and serum chemistry evaluation. created new challenges in the treatment of women
Evidence of haemolysis with elevated lactate de- with this disease.
hydrogenase levels may be encountered and is
attributed to endotoxin-mediated haemolysis.''^''' 2. Complications of Acute Pyeioneptiritis
Electrolyte abnormalities are also common. Tran- in Pregnancy
sient renal insufficiency as demonstrated by a
decrease in creatinine clearance by 50% or more There are both maternal and fetal complica-
occurs in some women. Previous estimates tions of acute pyelonephritis in pregnancy. Anaemia
were that a quarter of women with acute pyelo- is the most common complication encountered
nephritis in pregnancy developed renal insuffi- in association with the disease, occurring in ap-
ciency,'^-''' but modern studies suggest that the proximately 25% of patients.'"*' Approximately
rate may be lower (2%), possibly due to earlier 15-20% of women with pyelonephritis will have
presentation for treatment and intravenous fluid bacteraemia.'^l Gram-negative bacteria possess
hydration.''*'^*'' Spontaneous resolution of the ab- endotoxins that, when released into the maternal
normal renal function should be expected as the circulation, can lead to a cascade response of
acute infection clears. cytokines, histamine and bradykinins.'""*' The re-
Blood cultures are often obtained when pyelo- sulting capillary endothelial damage, diminished
nephritis is suspected, although the utility of vascular resistance and alterations in cardiac
this practice has been questioned since the iso- output may lead to serious complications such
lates of blood cultures rarely differ from those of as septic shock, disseminated intravascular co-
urine cultures.l-'*'^''' In a retrospective study of agulation, respiratory insufficiency or ARDS.
f 2010 Adis Data Information BV. Aii rigiits reserved. Drugs 2010, 70(13)
1646 Jolle}/ & Wing
considered carefully as there is the potential for en effectiveness in properly conducted, prospec-
ototoxicity with their use. To date, gentamicin tive, randomized, double-blind trials; (ii) activity
has been widely used in pregnancy as first-line against the uropathogens likely to be responsi-
therapy for Gram-negative coverage with no re- ble for the symptomatic upper UTI; (iii) ability to
ports of congenital complications. However, it is maintain adequate tissue and serum concentra-
a Food and Drug Administration (FDA) cate- tions throughout the treatment period; (iv) lack
gory C drug in the US, meaning that studies have of association with the development of resistance
shown that the drug exerts teratogenic or em- to antibacterials; (v) inexpensive; (vi) well tolerat-
bryocidal effects in animals, but there are no ed; and (vii) safety for the developing fetus. There
controlled trials in women. In addition, ototoxi- are insufficient data to recommend a specific
city has been demonstrated following fetal ex- treatment regimen for pyelonephritis in pregnancy
posure to related aminoglycoside compounds as few studies exist comparing the efficacy of
such as kanamycin and streptomycin.'"''"'''' Acute different antibacterial agents.'^^"^^' A Cochrane
renal dysfunction associated with pyelonephritis Database review found that all antibacterials stud-
appears to be less common'"*' than the 20% rate ied were effective in clearing infections and de-
noted previously;'^' thus, empirical treatment creasing the incidence of complications such as
with gentamicin while awaiting serum creatinine prolonged pyrexia and preterm delivery.'^'' Many
measurement may be appropriate. However, if regimens are acceptable and appear to be effec-
gentamicin is chosen, monitoring of serum con- tive (table I).
centrations should be performed and adjustments Intravenous antimicrobial therapy is usually
made in the dose administration as needed. This continued until the patient is afebrile for 48 hours
is partly because of concerns regarding any toxic and symptoms have improved; afterward, the
effects such as exacerbation of renal insufficiency, patient is treated with oral antibacterials. The
but also because maternal serum concentrations course of oral therapy lasts for 10-14 days. After
near term are more likely to be subtherapeutic completion of therapy, a urine culture should
because of enhanced drug clearance.'^"''' be obtained to verify resolution of the bacteri-
The optimal antibacterial regimen for the uria. The appropriate duration of therapy for
treatment of acute pyelonephritis in pregnancy eradication of pyelonephritis has not been sub-
would be characterized by the following: (i) prov- jected to scientific scrutiny.
Table I. Examples of dosage administration regimens of antibacterial agents for the treatment of pyelonephritis in pregnancy with US FDA
classification for use in pregnancy
Agent Dosage (intravenous administration) Frequency FDA pregnancy class
Ampicillin (combined with gentamicin as below) 1-2 g q6h B
Gentamicin (may be given alone) 2 mg/kg to load then 1.7 mg/kg in three divided doses q8h C
Ampicillin/sulbactam 3g q6h B
Cefazolin 1-2 g q6-8h B
Ceftriaxone 1-2 g q24h B
Cefuroxime 0.75-1.5 g qSh B
Cefofaxime 1-2g q8-12h B
Cefepime lg q12h B
Cefofetan 2g q12h B
Mezlocillin 3g q6h B
Piperacillin 4g q8h B
Aztreonam" ig q8-12h B
a May be used in the setting of |i-lactam allergy.
q x h = every x hours.
a 2010 Adis Data Informafion BV. All righfs reserved. Drugs 2010: 70 (13)
1648 Jolky &
arate study corroborated that in the US, the vital.'^-] The IDSA published guidelines for de-
highest prevalence of multidrug-resistant pheno- veloping an institutional programme to enhance
types is found on the Pacific Coast.'] antimicrobial stewardship,'"'^] designed to opti-
Recent prior antibacterial treatment is one of mize clinical outcomes and minimize unintended
the most important determinants for infection with consequences of antimicrobial use including the
a resistant microbe.''"' Although there are several development of resistant organisms. Utilization
important differences between recommendations of these guidelines as well as a comprehensive
for treatment of gestational pyelonephritis and infection control programme may limit the
antimicrobials commonly used in uncomplicated emergence and transmission of antimicrobial-
UTI, the significance of antimicrobial steward- resistant bacteria.'^-'] Because resistance patterns
ship when selecting a treatment regimen remains vary with location and antibacterial therapy
Pyelonephritis diagnosed
Urine culture sent
Consider
outpatient
treatment
Signs of sepsis,
urinary tract abnormality,
medical co-morbidity
Ves
At completion of treatment
send urine culture as test of cure
Ensure appropriate treatment
based on urine culture sensitivities
2010 Adis Data Information BV, All rights reserved. Drugs 2010; 70(13)
1650 Jolley & Wing
is initiated empirically, knowledge of resistance sponse to the initial antibacterial therapy.'''^1 The
patterns in the local community may infiuence antibacterial sensitivity of the uropathogen did
the selection of the initial antimicrobial for treat- not predict clinical cure. Susceptibility testing for
ment of pyelonephritis in pregnant patients. antimicrobials established by the National Com-
mittee for Clinical Laboratory Standards is based
4.1 Antimicrobial-Resistant Uropathagens on serum concentrations.'^'^' In vitro resistance may
in Antepartum Pyeionepiiritis not adequately predict therapeutic failure because
the concentration of most antimicrobial agents used
It has been suggested that infections with for UTIs is higher in the urine than in serum.'''^' For
antimicrobial-resistant organisms may increase this reason, we advocate that changes in antibac-
the risk of complications and mortality.''''*' This terial therapy should be directed by clinical response
concept is of growing importance in the manage- rather than culture results alone. Surveillance of
ment of antepartum pyelonephritis as increasing microbial drug resistance at a given institution may,
rates of antimicrobial-resistant uropathogens are however, facilitate selection of the appropriate first-
id'2'"43] line antibacterial therapy.
g
Greer et al.'''"'I investigated the outcomes in
patients with acute antepartum pyelonephritis 5. Rationale for Hospitaiization
caused by ampicillin-resistant bacteria in a sec- of Pregnant Patients with
ondary analysis of a prospective cohort study. Pyeionephritis
After being diagnosed with pyelonephritis, every
patient was presumptively treated with ampiciiiin Over 20 years ago, the American College of
and gentamicin. Fifty-one percent of the or- Obstetricians and Gynecologists stated in a Techni-
ganisms identified with sufficient cfu to receive cal Bulletin that hospitaiization of pregnant women
antibacterial sensitivity testing were resistant to am- with pyelonephritis is necessary.'^''' Theoretically,
piciiiin, 92% of which were E. coli. The patients this approach will circumvent serious complica-
infected with ampicillin-resistant organisms were tions associated with pyelonephritis, including res-
more likely to be older and multiparous, but there piratory insufficiency, septic shock, preterm labour
were no significant differences in complications and delivery, and recurrences with the possibility ol"
between the groups. The rates of anaemia, renal permanent renal damage. However, the recommen-
dysfunction, respiratory insufficiency and pre- dation to hospitalize all women with pyelonephritis
term birth were comparable. There were also no was not based on evidence from clinical trials. The
significant differences in length of hospital stay, high cost of medical care and concerns for cost con-
days of intravenous antibacterials required, ad- tainment have provided motivation to study ambu-
mission to extended care unit or rate of hospital latory methods of therapy for the pregnant patient.
readmission. The results of this study appear to Because pyelonephritis is one of the most common
contradict the notion that antimicrobial-resistant reasons for hospitaiization during pregnancy, at-
tention has been directed toward developing a safe
organisms cause increased morbidity; however,
and effective approach to outpatient treatment of
an important consideration is that all of these
acute pyelonephritis. Based on the evidence pre-
women were concomitantly treated with genta-
sented in this review, this approach in pregnancy
micin, and all but one of the organisms cultured
has only limited utility.
was sensitive to this drug.''*-^'
There is possibly a difference between micro-
biological resistance and clinical resistance to 6. Ambuiatory Treatment of Acute
an antibacterial medication, as noted by Wing Pyeionephritis
et al.'-''-' in their study of the clinical utility of 6.1 Nonpregnant Patients
blood and urine cultures in the treatment of
pyelonephritis in pregnancy. In their analysis, As observational studies'""^^' and random-
94% of patients had an acceptable clinical re- ized controlled trials"*'''^'' have demonstrated the
safety of outpatient management of acute pyelo- 21 pregnant women with pyelonephritis in preg-
nephritis in nonpregnant patients, the hospitali- nancy at 26 weeks or earlier. Initial evaluation
zation rate for these patients has decreased from was for 2 hours in an obstetric emergency room
almost 100% to 7-30% in recent decades.''^**-^'*-^! with chnic follow-up for daily intramuscular in-
Most of the evidence for ambulatory treatment jections of ceftriaxone until both fever and CVAT
stems from data collected in emergency depart- resolved, then a 10-day course of oral antibac-
ments and investigations have reinforced the terials. The authors estimated that 50% of preg-
importance of careful patient selection for ambu- nant patients reporting to an obstetric emergency
latory therapy. Equally as important is the need room could be treated as outpatients. A later in-
for an initial period of observation for hydration vestigation with a different approach using home
and subsequent triage.1^'^! A meta-analysis of the health nurse visits after initial intramuscular
existing literature on oral therapy for pyelone- treatment in the emergency room followed by
phritis'**''! indicates that patients who do not have 10 days of oral cephalexin found 90% effective-
diabetes or sepsis and who are not immunocom- ness in 120 pregnant women at less than 24 weeks'
promised, can tolerate oral intake, and do not gestation.'-^**! Ten percent of the outpatients were
have chronic illness can be treated for upper UTI eventually hospitalized because of sepsis, abnor-
with oral agents. From these data, a regimen for mal laboratory tests, deviation from study pro-
the outpatient treatment of pregnant women with tocol and recurrent pyelonephritis while on oral
acute pyelonephritis may be extrapolated; how- therapy. Overall, the authors estimated that
ever, the application of ambulatory therapy for 5% of patients with pyelonephritis at less than
upper UTI in pregnancy appears to be quite 24 weeks" gestation who are considered candi-
limited. dates for outpatient therapy will not be able to be
2010 Adis Data Information BV. Ali rights reserved. Drugs 2010: 70 (13)
1652
Jolle}/ &
pyelonephritis after 24 weeks' gestation were not rates to empirically chosen antibacterial therapies
candidates for ambulatory therapy'**^' and, there- is mandatory. The period of observation should
fore, this approach is quite limited in the third be long enough to review laboratory results
trimester. and to assess the ability to tolerate oral intake,
There are no trials describing outpatient oral and the patient's clinical response to therapy. If
therapy for acute pyelonephritis in pregnancy. women with gestational ages beyond 24 weeks arc
to be managed on an ambulatory basis, even
6.3 Recommendations for Ambulatory longer periods of observation with continuous
Treatment of Pyelonephritis fetal heart rate and uterine activity monitoring
in Pregnancy are required to ensure both maternal and fetal
stability before discharge from the observation
Cumulatively, the results of the existing trials unit, although more recent data would indicate
are only encouraging for the ambulatory treat- that the risk of preterm delivery associated
ment of acute pyelonephritis in pregnancy in the with acute pyelonephritis is lower than previously
first and early second trimesters of pregnancy. estimated.''*'
Outpatient treatment of acute pyelonephritis in Emphasis must be placed on close outpatient
pregnancy beyond 24 weeks appears to have follow-up evaluation until both chnical and
limited utility, and it would appear most prudent microbiological cure are obtained. Follow-up
to admit women for conventional treatment with evaluation within 24 hours may take place in an
intravenous hydration and antibacterials if their office, clinic or emergency room. Alternatively,
gestational ages exceed this threshold. a home health nursing visit may be performed. At
Clearly, careful selection of appropriate can- this evaluation, an additional dose of ceftriaxone
didates for outpatient therapy of acute pyelone- should be given and an assessment made of the
phritis in pregnancy is required. Patients should chnical condition. After the second dose, the anti-
be less than 24 weeks pregnant, relatively healthy bacterial may be changed to oral cephalexin
and able to comply with outpatient therapy. They 500 mg four times a day (or a similar substitute)
should not have excessive fever (>38C), severe for 10 days, or daily intramuscular administra-
nausea and vomiting, recurrent upper urinary tion could be continued until all symptoms have
tract disease, signs of sepsis including tachypnoea, resolved. The daily intramuscular administration
tachycardia, rigors or hypotension, immuno- regimen does not exceed 5 days. If the change
compromise, significant medical conditions such to oral therapy is made, another outpatient
as diabetes or previous renal disease, history of clinical evaluation should be made within the
substance abuse, concurrent preterm labour or 24 hours after the change. After completion of the
uncertain diagnosis. Liberalizing the criteria for daily ceftriaxone, oral treatment for 7-10 days
outpatient therapy, in the absence of supporting is continued with cephalexin or with another
data, may lead to serious detriment. antibacterial to which the causative organism is
A period of observation is required, during susceptible.
which the patient should be hydrated and anti- Clinic follow-up evaluation within 2 weeks
bacterial therapy with intramuscular ceftriaxone after acute therapy should also be required.
initiated. Laboratory studies (complete blood cell A urine culture should also be obtained as a
count, serum chemistry panel including serum 'test of cure". Throughout the remainder of the
blood urea nitrogen and creatinine, and urine pregnancy, the patient should be followed for
culture) should be obtained. Although urine cul- symptoms of recurrent infection and monthly
ture may not aid in the immediate clinical man- urine cultures should be performed until delivery.
agement, approximately 6-10% of patients will Antimicrobial prophylaxis should be initiated
not be successfully treated in an ambulatory set- in all patients for the remainder of the preg-
ting and the results of the cultures may guide nancy and should be continued until 4-6 weeks
subsequent therapy. Surveillance of resistance postpartum.
25. Mobley HLT, Island MD, Massad G. Virulenee determi- 45. Frimodt-Maller N. Correlation between pharmacokinetic/
nants of uropathogenic Escherichiii coli and Proleus mir- pharmacodynamic parameters and efTicacy for antibiotics
ahili.s. Kidney Int Suppl 1994 Nov; 47: S129-.16 in the treatment of urinary tract infection. Int J Antimicroh
26. Cox SM. Shelburne P. Mason R, et al. Mechanisms of Agents 2002 Jun; 19 (6); 546-53
hemolysis and anemia associated with acute antepartum 46. Nicolle L. Uncomplicated urinary tract infection in adults
pyelonephritis. Am J Obstet Gynecol 1991 Feb; 164 (2) including uncomplicated pyelonephritis. Urol Clin North
587-90 Am 2008 Feb; 35(1): 1-12
27. Whalley PJ, Cunningham FG. Martin FG. Transient renal 47. Nishimura H, Tanimura T. Clinical aspects of the terato-
dysfunction associated with acute pyelonephritis of preg- genicity of drugs. New York: Excerpta Medica, 1976: 130
nancy. Obstet Gynecol 1975 Aug; 46 (2): 174-7
48. Jones HC. Intrauterine ototoxicity: a case report and revie
28. Sheffield J. Cunningham FG. Llrinary tract infection in of the literature. J Nati Med Assoc 1973 May; 65 (3): 201-.^
women. Obstet Gynecol 2005 Nov; 106 (5 Pt 1): 1085-92
49. Donald PR, Sellars SL. Streptomycin toxicity in the unborn
29. MacMillan MC. Grimes DA. The limited usefulness of urine child. S Afr Med J 1981; 60: 316-8
and blood cultures in treating pyelonephritis in pregnancy. 50. Graham JM, Blanco JD, Oshiro BT, et al. Gentamicin levels
Obstet Gynecol 1991 Nov; 78 (5 Pt 1); 745-8
in pregnant women with pyelonephritis. Am J Perinatal
30. McMurray BR. Wrenn KD, Wright SW. Usefulness of 1994 Jan; U (l):40-l
blood eultures in pyelonephritis. Am J Emerg Med 1997 51. Lazebnik N. Noy S. Lazebnik R, et al. Gentamicin serum
Mar; 15(2); 137-40
halflife: a comparison between pregnant and nonpregnant
31. Thanassi M. Utility of urine and blood cultures in pyelo- women. Postgrad Med J 1985 Nov; 61 (721): 979-81
nephritis. Acad Emerg Med 1997 Aug; 4 (8): 797-800 52. Gilbert T, Leiievre-Pegorier M, Malienou R, et al. Effects of
32. Wing D, Park AS. DeBuque L, et al. Limited clinical utility prenatal and postnatal exposure to gentamicin on renal
of blood and urine cultures in the treatment of acute pyelo- differentiation in the rates. Toxicology 1987 Mar- 43 (3)-
nephritis during pregnaney. Am J Obstet Gynecol 2000 301-13 -
Jun; 182(6): 1437-41 53. Cox SM, Cunningham FG. Ureidopenicillin therapy for
33. Velasco M. Martinez JA. Moreno-Martinez A, et al. Blood acute antepartum pyelonephritis. Curr Ther Res 1988
cultures for women with uncomplicated acute pyeloneph- 44(6): 1029-34
ritis: are they necessary? Clin Infect Dis 2003 Ocf 37 (8)- 54. Angel JL, O'Brien WF, Finan MA, et al. Acute pyelo-
1127-30 nephritis in pregnancy: a prospective study of oral versus
34. Chen Y, Nitzan O, Saliba W, et al. Are blood cultures intravenous antibiotic therapy. Obstet Gynecol 1990 Jul
necessary in the management of women with complicated 76(1): 28-32
pyelonephritis? J Infect 2006 Oct; 53 (4): 235-40 55. Sanchez-Ramos L, McAlpine KJ, Adair CD, et al. Pyelo-
35. Lucas MJ. Cunningham FG. Urinary infeetion in preg- nephritis in pregnancy: once-a-day ceftriaxone versus
nancy. Clin Obstet Gynecol 1993 Dec; 36 (4): 855-68 multiple doses of cefazolin. Am J Obstet Gynecol 1995 Jan
36. Bates DW, Cook EF. Goldman L. et al. Predicting bacter- 172(1 Pt 1): 129-33
emia in hospitalized patients: a prospectively validated 56. Izquierdo LA, Johnson J, Del Valle GO, et al. Acute
model. Ann Intern Med 1990 Oct; 113 (7): 495-500 pyelonephritis in pregnancy: a randomized study of three
37. Wing DA. Pyelonephritis in pregnancy: treatment options antibiotic treatment regimens. Prenat Neonat Med 1996- \-
for optimal outcomes. Drugs 2001; 61 (14): 2087-96 355-8
38. Mittal P. Wing DA. Urinary tract infeetions in pregnaney. 57. Brooks AM. Garite TJ. Clinical trial of the outpatient
Clin Perinatol 2005 Sep; 32 (3): 7499-64 management of pyelonephritis in pregnancy. Infect Dis
Obstet Gynecol 1995; 3 (2): 50-5
39. Cunningham FG, Lucas MJ. Hankins GDV. Pulmonary
injury complicating antepartum pyelonephritis. Am J Ob- 58. Millar LK. Wing DA. Paul RH. et al. Outpatient treatment
stet Gynecol 1987 Apr; 156 (4): 797-807 of pyelonephritis in pregnancy: a randomized controlled
trial. Obstet Gynecol 1995 Oct; 86 (4 Pt 1): 560-4
40. Towers CV, Kaminskas CM, Garite TJ, et al. Pulmonary
injury associated with antepartum pyelonephritis; can 59. Vazquez JC. Villar J. Treatments for symptomatic urinary
patients at risk be identified? Am J Obstet Gynecol 1991 tract infections during pregnancy. Cochrane Database Syst
Apr; 164 (4): 974-80 Rev 2003; (4): CD002256
41. Graham JM. Oshiro BT. Blanco JD. et al. Uterine contrac- 60. Wing DA, Hendershott CM, DeBuque L, et al. A random-
tions after antibiotic therapy for pyelonephritis in preg- ized trial of three antibiotic regimens for the treatment of
nancy. Am J Obstet Gyneeol 1993 Feb; 168 (2): 577-80 pyelonephritis in pregnancy. Obstet Gynecol 1998 Aug
92 (2): 249-53
42. Millar LK, DeBuque L. Wing DA. Uterine contraction fre-
quency during treatment of pyelonephritis in pregnancy 61. Lenke RR. VanDorsten JP, Schifrin BS. Pyelonephritis in
and subsequent risk of preterm birth. J Perinat Med 2003- pregnancy: a prospective randomized trial to prevent re-
31(1): 41-6 current disease evaluating suppressive therapy with nitro-
furantoin and close surveillance. Am J Obstet Gynecol
43. Greer LG, Roberts SW, Sheffield JS. et al. Ampicillin resis- 1983 Aug: 146 (8): 953-7
tance and outcome differences in acute antepartum pyelo-
nephritis. Infect Dis Obstet Gynecol 2008; 2008: 891426 62. VanDorsten JP. Lenke RR, Schifrin BS. Pyelonephritis in
pregnancy: the role of in-hospital management and nitro-
44. Niebyl JR. Antibiotics and other anti-infectives in pregnancy furantoin suppression. J Reprod Med 1987 Dec- 32 (12)-
and lactation. Am J Perinatol 2003 Nov; 20 (8): 405-14 895-900
()3. Sandberg T. Brorson JE. Efficacy of long-term anti- 76. Committee on Obstetrics. Antimicrobial therapy for ob-
microbial prophylaxis after acute pyelonephritis in preg- stetric patients. Washington, DC; American College of
nancy. Scand J Infect Dis 1991; 23 (2): 221-.'i Obstetricians and Gynecologists, 1988. American Col-
64. Briggs G. Freeman R. Yaffe S. Drugs in pregnancy and lege of Obstetricians and Gynecologists Technical Bulletin
lactation. 7th ed. Philadelphia (PA): Lippincott Williams & no.117
Wilkins, 2005: 1508-9 77. Safrin S, Siegel D. Black D. Pyelonephritis in adult women;
(i5 Christensen F. Which antihiotics are appropriate for treat- inpatient versus outpatient therapy. Am J Med 1988 Dec;
ing bacteriuria in pregnancy? J Antimicrob Chemother 85 (6); 793-8
2000 Sep; 46 Suppl. 1: 29-34 78. Ward G. Jordan RC, Severance HW. Treatment of pyelo-
66. Warren JW. Ahrutyn E. Hehel JR. et al. Guidelines for nephritis in an observation unit. Ann Emerg Med 1991
antimicrobial treatment of uncomplicated acute bacterial Mar; 20 (3); 258-61
cystitis and acute pyelonephritis in women; Infectious 79. Israel RS, Lowenstein SR. Marx JA. et al. Management
Diseases Society of America (lDSA). Clin Infect Dis 1999 of acute pyelonephritis in an emergency department
Oct; 29 (4): 745-58 observation unit. Ann Emerg Med 1991 Mar; 20 (3);
67. Zhanel GG. Hisanaga TL. Laing NM. et al. Antibiotic re- 253-7
sistance in outpatient urinary isolates: final results from the 80. Talan DA. Stamm WE, Hooton TM. et al. Comparison of
North American Urinary Tract Infection Collaborative ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole
Alliance (NUTICA). Int J Antimicrob Agents 2005 Nov; (14 days) for acute uncomplicated pyelonephritis in
26 (5): 380-8 women; a randomized trial. JAMA 2000 Mar; 283 (12):
68. Stamm WE. Scientific and clinical challenges in the man- 1583-90
agement of urinary tract infections. Am J Med 2002 Jul; 81. Klausner HA, Brown P, Peterson J, et al. A trial of levo-
113 Suppl. lA: 1-4S floxacin 750 mg once daily for 5 days versus ciprofloxacin
69. Kashanian J. Hakimian P. Blute M. et al. Nitrofurantoin; 400 mg and/or 500 mg twice daily for 10 days in the treat-
the return of an old friend in the wake of growing resis- ment of acute pyelonephritis. Curr Med Res Opin 2007
Nov; 23 (11); 2637-45
tance. BJU Int 2008 Dec; 102 (111); 1634-7
82. NicoUe LE, Friesen D, Harding GK. et al. Hospitaiization
70. Sannes MF, Kuskowski MA, Johnson JR. Geographical
for acute pyelonephritis in Manitoba. Canada, during the
distrihution of antimicrobial resistance among Escherichia
period from 1989 to 1992: impact of diabetes, pregnancy,
coli causing acute uncomplicated pyelonephritis in the
and aboriginal origin. Clin Infect Dis 1996 Jun; 22 (6);
United States. FEMS Immunol Med Microbiol 2004 Oct;
1051-6
42 (2); 213-8
83. Foxman B, Klemstine KL, Brown PD. Acute pyelonephritis
71. Gupta K. Addressing antibiotic resistance. Am J Med 2002
in US hospitals in 1997; hospitaiization and in-hospital
Jul; 113(1A);29S-34S
mortality. Ann Epidemiol 2003 Feb; 13 (20); 144-50
72. Hooton TM, Besser R, Foxman B, et al. Acute un-
84. Pinson AG. Philbrick JT, Lindbeck GH, et al. Oral anti-
complicated cystitis in an era of increasing antibiotic re-
biotic therapy for acute pyelonephritis; a mthodologie
sistance: a proposed approach to empirical therapy. Clin
review of the literature. J Gen Intern Med 1992 Sep-Oct;
Infect Dis 2004 Jul; 39 (1): 75-80
7 (5); 544-53
73. Dellit TH, Owens RC, McGowan Jr JE. et al. Infectious
85. Wing DA. Hendershott CM, DeBuque L, et al. Outpatient
Diseases Society of America and the Society for Healthcare
treatment of acute pyelonephritis in pregnancy after
Epidemiology of America guidelines for developing an in-
24 weeks. Obstet Gynecol 1999 Nov; 94 (5 Pt 1); 683-8
stitutional program to enhance antimicrobial stewardship.
Clin Infect Dis 2007 Jan; 44 (20): 159-77
74. Melzer M. Petersen I. Mortality following bacteraemic
infection caused by extended spectrum beta-lactamase Correspondence: Dr Deborah A. Wing, University of
(ESBL) producing E. coli compared to non-ESBL produ-
California, Irvine, Department of Obstetrics and Gynecol-
cing . coll. J Infect 2007 Sep; 55 (3); 254-9
ogy, 101 The City Drive, Building 56, Suite 800, Orange,
75. Le J. Briggs GG, McKeown A, et al. Urinary tract infections
during pregnancy. Ann Pharmacother 2004 Oct; 38 (10); CA 92868, USA.
1692-701 E-mail; mfm@ud.edu