Original Articleswitch therapy after treatment for acute pyelonephritis caused by Chitprasong Malaisria, Angsana Phuphuakrata, Arrug Wibulpolprasertb, Pitak Santanirandc, Sasisopin Kiert
Trang 1Original Article
switch therapy after treatment for acute pyelonephritis caused by
Chitprasong Malaisria, Angsana Phuphuakrata, Arrug Wibulpolprasertb,
Pitak Santanirandc, Sasisopin Kiertiburanakula,*
a Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
b Department of Emergency Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
c Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
a r t i c l e i n f o
Article history:
Received 23 January 2017
Received in revised form
8 April 2017
Accepted 11 May 2017
Available online xxx
Keywords:
Pyelonephritis
Ertapenem
Extended-spectrum beta lactamase (ESBL)
Escherichia coli
Sitafloxacin
a b s t r a c t
Background: The overuse and misuse of carbapenems have contributed to the antibiotic resistance crisis The role of oralfluoroquinolones as a switch therapy for the treatment of urinary tract infection from Escherichia coli (ESBL-EC) is limited
Objective: To compare the clinical and bacteriological efficacy of sitafloxacin and ertapenem for non-bacteremic acute pyelonephritis caused by ESBL-EC
Methods: A prospective randomized controlled trial of patients with acute pyelonephritis caused by ESBL-EC was performed as a pilot study One of the carbapenems was initially given to the patients After day 3, patients were randomized to receive either sitafloxacin or ertapenem
Results: Thirty-six patients were enrolled: 19 (52.8%) in the sitafloxacin group and 17 (47.2%) in the ertapenem group There was no statistically significant difference in baseline characteristics between the two groups except a lower proportion of previous urinary catheter insertion in the sitafloxacin group (15.8% vs 52.9%, p¼ 0.018) Signs and symptoms at presentation were similar between the two groups except a higher proportion of patients with chills in the sitafloxacin group (68.4% vs 29.4%, p ¼ 0.019) At day 10, all but one patient in the ertapenem group had clinical cure Microbiological eradication was comparable between the sitafloxacin and ertapenem groups (84.2% vs 75%, p ¼ 0.677) There were no significant adverse effects
Conclusions: Treatment of non-bacteremic acute pyelonephritis caused by ESBL-EC with carbapenem followed by oral sitafloxacin is effective and well-tolerated Sitafloxacin may be considered as an alter-native choice of switch therapy in this clinical setting
© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
Published by Elsevier Ltd All rights reserved
1 Introduction
As many as 80% of urinary tract infections (UTIs) are caused by
Escherichia coli [1,2] Since the first clinical isolation in 1983,
extended-spectrumb-lactamase (ESBL)-producing organisms have become recognized as a worldwide problem, and their incidence has been increasing[3,4] ESBLs, which are found predominantly in Klebsiella pneumoniae and E coli, can hydrolyze all penicillins, cephalosporins, and monobactams[5], but they do not affect car-bapenems (e.g imipenem or meropenem) Cephamycins (e.g cefoxitin and cefotetan) are not hydrolyzed by majority of ESBLs, but they are hydrolyzed by associated AmpC-type b-lactamase ESBL-producing E coli (ESBL-EC) are now a frequent cause of infection in the community and in healthcare centers [6e8] In recent years, an increase in infection with such ESBL-producing organisms has been observed in outpatient settings, especially
* Presentation: Parts of this manuscript were presented at the 24th European
Congress of Clinical Microbiology and Infectious Diseases (Barcelona), May 10e13,
2014 [abstract P0253].
* Corresponding author Division of Infectious Diseases, Department of Medicine,
Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400,
Thailand Fax: þ66 2 201 2232.
E-mail address: sasisopin.kie@mahidol.ac.th (S Kiertiburanakul).
Contents lists available atScienceDirect
Journal of Infection and Chemotherapy
jo u rn a l h o m e p a g e :h t t p : / / w w w e l s e v i e r c o m / l o c a t e / j i c
http://dx.doi.org/10.1016/j.jiac.2017.05.005
1341-321X/© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Published by Elsevier Ltd All rights reserved.
J Infect Chemother xxx (2017) 1e7
Trang 2related to UTIs, and treatment options have been reduced to a
limited number of antibiotics[9e11]
Treatment of infection with ESBL-EC is difficult because the
or-ganisms are frequently resistant to multiple antibiotics
Carbape-nems, which are not affected by ESBLs, are considered the drugs of
choice for treating severe infections caused by ESBL-producing
organisms In vitro, ESBL-producing organisms may sometimes
appear to be susceptible tob-lactams/b-lactamase inhibitors,
third-and fourth-generation cephalosporins, aminoglycosides, third-and
fluo-roquinolones Susceptibility rates for these antibiotics are 0e80%,
depending on the geographical location of the study site[12,13]
Clinicians are increasingly considering using carbapenems either as
empiric or definitive therapy in moderate or severe
community-onset and nosocomial infections whenever an ESBL-producing
or-ganism is suspected or demonstrated This may be leading to an
increase in the consumption of carbapenems, which is particularly
worrisome in a scenario where carbapenemase-producing
organ-isms are also spreading [14,15] In addition, widespread use of
carbapenems may be associated with further selection of
patho-gens with acquired (K pneumoniae, Pseudomonas aeruginosa, and
Acinetobacter baumannii) and inherited (Stenotrophomonas
malto-philia) antibiotic resistance[16,17] Thus, alternatives to
carbape-nems for the treatment of ESBL-producing organism infections are
urgently needed
Fluoroquinolones may be considered as the treatment of choice
for UTIs due to ESBL-producing organisms if there is no in vitro
resistance to fluoroquinolones [18] Unfortunately, increasing
in vitro resistance of ESBL-producing organisms tofluoroquinolones
could limit the role of these antibiotics in the future [6]
Sita-floxacin, a broad-spectrum oral fluoroquinolone, is active against
many gram-positive, gram-negative, and anaerobic bacteria,
including strains resistant to other fluoroquinolones[19] It was
approved in Japan for the treatment of respiratory tract infection
and genitourinary tract infection Several in vitro activity studies
regarding sitafloxacin have been conducted showing that
sita-floxacin is very active against a variety of bacteria, including
Streptococcus pneumoniae, Staphylococcus aureus,
Enterobacteri-aceae, P aeruginosa, A baumannii, and Bacteroides fragilis[20e24]
Furthermore, a recent in vitro activity study found that sitafloxacin
is more active than levofloxacin, ciprofloxacin, and moxifloxacin
against bacteria isolated from patients with UTIs, including
antibiotic-resistant bacteria such as ESBL-producing
gram-nega-tives, and carbapenem-resistant A baumannii[25]
The aim of our study was to evaluate sitafloxacin as compared to
ertapenem as a switch therapy for the treatment of non-bacteremic
acute pyelonephritis caused by ESBL-EC Clinical and bacteriological
outcomes of participants were evaluated We hypothesized that if
sitafloxacin could be successfully applied in this clinical setting, the
lower rate of carbapenem use might reduce multi-drug resistant
organism problems
2 Materials and methods
2.1 Study design
A prospective, open-label, randomized, controlled trial was
conducted at Ramathibodi Hospital, a 1200-bed university hospital
in Bangkok, Thailand, from November 2012 to June 2015 Written
informed consent was obtained from all patients The protocol was
approved by the institutional review board of the Faculty of
Med-icine Ramathibodi Hospital, Mahidol University This study was
registered at ClinicalTrials.gov under registration number
NCT02537847
When the results of urine culture were reported, the patients
were then allocated to oral sitafloxacin treatment or intravenous
(IV) ertapenem treatment in a 1:1 ratio After randomization, all patients were initially given one of the IV carbapenems for 3 days and then switched to oral sitafloxacin or IV ertapenem Carbape-nems included meropenem 1 gm IV every 8 h, imipenem 500 mg IV every 6 h, doripenem 500 mg IV every 8 h, and ertapenem 1 gm IV once daily Randomization was performed using a computer-generated random number allocation schedule with a block size
of four The patients were allocated to the sitafloxacin group or the ertapenem group determining by the sealed envelope method The total duration of antibiotic treatment was 10 days
2.2 Patients Both hospitalized and non-hospitalized patients were consid-ered eligible if they: (1) were over 18 years of age; (2) had a pre-sumptive diagnosis of acute pyelonephritis, defined as pyuria (10 leukocytes per high-powerfield (HPF) in urine analysis) combined with all of the following: fever (body temperature 38C), urinary
syndrome (dysuria, urgency, or urinary frequency),flank pain, or costovertebral angle tenderness; (3) had positive urine culture of
105colony-forming units (CFU)/mL ESBL-EC; and (4) voluntarily consented to be enrolled in the study Exclusion criteria were as follows: (1) urine culture growing more than one organism; (2) severe sepsis or septic shock; (3) positive hemoculture; (4) had other sources of infection; (5) known mechanical abnormality of the urinary tract; (6) immunocompromised host, e.g receiving prednisolone >15 mg/day, post-organ transplantation, aplastic anemia, or solid and hematologic malignancy receiving chemo-therapy; (7) retaining Foley catheter; (8) pregnancy or lactation; (9) previous UTIs within four weeks; and (10) contraindication to flu-oroquinolones and/or carbapenems
All eligible patients were given one of the carbapenems as an initial antibiotic agent After day 3, patient were enrolled and randomized to either the sitafloxacin or ertapenem group All an-tibiotics were renally adjusted according to creatinine clearance (CrCl), as calculated by the CockcrofteGault equation For patients receiving sitafloxacin, the dosage for those with CrCl more than
50 mL/min was 100 mg twice daily Among patients with renal impairment, the dosage was 50 mg once daily for patients with CrCl
30e50 mL/min and 50 mg every 48 h for those with CrCl 10e30 mL/ min Patients who were allocated to the ertapenem group were given ertapenem 1 g infused over 30 min once daily; the dosage was 0.5 g once daily for patients with CrCl<30 mL/min
On the day of enrollment, initial laboratory evaluation included complete blood count (CBC), hemoculture, serum creatinine (Cr), alanine aminotransferase (ALT), urinalysis (UA), and urine culture (UC) The follow-up laboratory monitoring at day 3 and day 10 included CBC, hemoculture, ALT (day 10 only), UA, and UC On day 7, clinical assessment of treatment outcomes, both symptoms and drug tolerability, was performed by interviewing the patients at the ward or via telephone if the patient had been discharged Adher-ence to medication was checked by pill-counting and medical re-cords The tolerability of study drugs and occurrence of adverse events (AEs) were evaluated by a physician At the last follow-up visit on day 30, UA and UC were reassessed The patients were evaluated for clinical signs and symptoms of acute pyelonephritis at the clinic on day 10 and day 30 During the study period, based on clinical judgment the physician could terminate the treatment for safety reasons or due to abnormal laboratoryfindings attributed to sitafloxacin or ertapenem administration
2.3 Study outcomes The clinical responses were based on clinical signs and symp-toms of acute pyelonephritis as determined by physical
C Malaisri et al / J Infect Chemother xxx (2017) 1e7 2
Trang 3examination, including body temperature, costovertebral angle
tenderness, and urinary syndrome Primary clinical outcomes were
cure vs failure at day 10 Cure was defined as free of symptoms;
failure was defined as persistent symptoms Secondary clinical
outcome was recurrent which was defined as new onset of clinical
signs and symptoms at the end of the study or at day 30
The bacteriological responses were assessed by quantitative
urine culture at day 10 It was categorized as either: (1) eradication,
defined as yielding sterile UC; (2) persistence, defined as 104CFU/
mL ESBL-EC grown from UC; or (3) superinfection, defined as an
emergence of a new bacterial isolate (another organisms, not
ESBL-EC)105CFU/mL grown from UC
2.4 Microbiology
All hemoculture and UC isolates were identified at the
micro-biology laboratory, Department of Pathology, Faculty of Medicine
Ramathibodi Hospital All isolates were tested for ESBL production
by the combined disk method, according to Clinical and Laboratory
Standards Institute (CLSI) recommendations[26] Pathogens
iden-tified from UC were tested for in vitro susceptibility to ampicillin,
gentamicin, amikacin, amoxicillin/clavulanic acid, piperacillin/
tazobactam, cefuroxime, ceftriaxone, ceftazidime, cefepime,
ami-kacin, trimethoprim/sulfamethoxazole, ciprofloxacin, levofloxacin,
ertapenem, imipenem, meropenem, colistin, and tigecycline by the
minimal inhibitory concentration (MIC) method, following the CLSI
2012 guidelines In vitro susceptibility to sitafloxacin was
deter-mined by the disk diffusion method The resistance breakpoint
used for sitafloxacin was >2 mg/L (zone size <16 mm)[27]
2.5 Statistical analysis
The intention-to-treat principle was applied based on the initial
treatment assignment and not on the treatment eventually
received Median with interquartile range (IQR) and frequencies (%)
were used to describe patients' characteristics Chi-square or
Fisher's exact test was used to compare categorical variables
be-tween the two groups Student's t test or ManneWhitney U was
used to compare continuous variables between the two groups All
p-values were two-tailed with those less than 0.05 considered
statistically significant Stata version 12.0 (StataCorp, College
Sta-tion, TX, USA) was used for all statistical analysis
3 Results
Thirty-six patients (24 women and 12 men) with a presumptive
diagnosis of acute pyelonephritis were enrolled (Fig 1) They were
randomized into either the sitafloxacin group (19 patients, 52.8%)
or the ertapenem group (17 patients, 47.2%) One patient in the
ertapenem group passed away from secretion obstruction on day 7
after randomization Baseline characteristics, clinical signs and
symptoms, laboratory results, and risk factors for
antimicrobial-resistant uropathogens of both groups were generally
compara-ble There was no statistically significant difference in baseline
characteristics between the two groups except there was a higher
proportion of previous urinary catheter insertion during the last 3
months in the ertapenem group (52.9% vs 15.8%, p¼ 0.018) Signs
and symptoms at hospital presentation were similar except a
higher proportion of patients with chills in the sitafloxacin group
(68.4% vs 29.4%, p¼ 0.019) Baseline characteristics of the patients
are shown inTable 1
All patients had good compliance They received a seven-day
course of either sitafloxacin or ertapenem according to the
proto-col The outcomes of treatment at day 10 were as the following; the
clinical cure rates were 100% in the sitafloxacin group and 94.1% in
the ertapenem group (p¼ 0.472) Bacterial eradication was 84.2% and 75.0% in sitafloxacin and ertapenem groups, respectively (p¼ 0.472) Two patients in the sitafloxacin group had persistent ESBL-EC infection One patient in the sitafloxacin group and four patients in the ertapenem group had superinfection Urine culture
of one patient in sitafloxacin group grew 105 CFU/mL of ESBL-producing K pneumoniae (ESBL-KP) and that of four patients in the ertapenem group grew Enterococcus spp
For the outcomes of treatment at day 30, two patients in the sitafloxacin group had recurrent acute pyelonephritis Clinical and bacteriological outcomes of the two groups are shown inTable 2 The stratified analysis by complicated (n ¼ 31) and uncomplicated pyelonephritis (n¼ 5) condition was performed Complicated py-elonephritis was defined as male, age >60 years, had diabetes mellitus or malignancy, receiving steroid, chemotherapy or radia-tion, and having anatomical/functional abnormality of the urinary system There was no statistically significant different in clinical cure rate at day 10 among patients with complicated pyelonephritis (100% in sitafloxacin group vs 93.8% in ertapenem group,
p¼ 0.999) and those with uncomplicated pyelonephritis (100% in sitafloxacin group vs 100% in ertapenem group, p ¼ 0.999) In addition, there was no statistically significant different in recurrent rate at day 30 among patients with complicated pyelonephritis (6.7% in sitafloxacin group vs 0% in ertapenem group, p ¼ 0.999) and those with uncomplicated pyelonephritis (25% in sitafloxacin group vs 0% in ertapenem group, p¼ 0.999)
Antibiotic susceptibilities of 36 isolates of ESBL-EC were all susceptible to tested carbapenems including ertapenem, imipe-nem, meropeimipe-nem, and doripenem They also showed high sus-ceptible rate to sitafloxacin (94.4%) comparing to ciprofloxacin (25.0%) and levofloxacin (25.0%) In addition, amikacin showed a similar susceptible rate as sitafloxacin while only 30.6% were sus-ceptible to gentamicin (Table 3) All ESBL-EC isolated from patients
in sitafloxacin group were susceptible to sitafloxacin
AEs were observed in one patient in the sitafloxacin group, giving an incidence of 5.3% This patient developed diarrhea, but the symptom resolved spontaneously within 3 days Sitafloxacin was continued without any remedial action Liver function test findings were within the normal range in both groups
4 Discussion Our primary aim was tofind an oral antimicrobial agent that could be substituted for IV carbapenem for the treatment of acute pyelonephritis caused by ESBL-EC as a switch therapy This study was thefirst randomized controlled trial regarding the use of flu-oroquinolones for treatment of this condition The results indicated that the overall clinical cure rate of acute pyelonephritis caused by ESBL-EC infection and the microbiological outcome of patients receiving sitafloxacin were not significantly different from those who received ertapenem, when sitafloxacin was used as a switch therapy after empirical carbapenem treatment
The only current proven therapeutic option for severe infections caused by ESBL-producing organisms is the carbapenem family However, carbapenems are currently available only in IV form The option of using ertapenem once a day makes it a useful parenteral antimicrobial agent for the treatment of serious UTIs in nursing homes and outpatient health care settings [28,29] Ertapenem is also an ideal choice for outpatient parenteral antibiotic therapy (OPAT) because of its once-daily dosage Previous studies have found that OPAT results in considerable cost savings compared with inpatient care[30], while at the same time being preferred by most patients [31] However, some patients are not comfortable receiving OPAT, and it might induce a local IV reaction, such as phlebitis
C Malaisri et al / J Infect Chemother xxx (2017) 1e7 3
Trang 4Assessed for eligibility (n=36)
Randomized (n = 36)
Allocated to sitafloxacin (n = 19) Received allocated intervention (n = 19)
Allocated to ertapenem (n = 17) Received allocated intervention (n = 17)
Lost to follow-up at day 30 (n = 4)
Lost to follow-up at day 30 (n = 3)
Died from secretion obstruction (n = 1)
Fig 1 Flow diagram of enrollment of patients with acute pyelonephritis.
Table 1
Baseline characteristics of the 36 patients.
Median (IQR) duration of fever, days 2 (1.0e3.0) 1 (1.0e2.0) 0.851 Risk factors for antimicrobial-resistant uropathogens in the last 3 months, n (%)
Clinical signs and symptoms, n (%)
Underlying disease, n (%)
Laboratory data
Median (IQR) white blood cells at day 0, cells/mm 3 12,870 (11,010e15,800) 11,850 (9680e17,870) 0.438 Median (IQR) white blood cells at day 3, cells/mm 3 7330 (6100e11,680) 8000 (6500e9500) 0.812 Median (IQR) baseline white cells in urine, cells/HPF 75 (35e200) 150 (75e200) 0.548 Median (IQR) baseline serum creatinine, mg/dL 1.03 (0.91e1.16) 1.03 (0.78e1.58) 0.824 Median (IQR) baseline ALT, U/L 51.0 (32.0e91.0) 46.0 (29.0e55.0) 0.326 ALT, alanine aminotransferase; COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus; HPF, high-power field; IQR, interquartile range.
a Urinary syndrome: dysuria, urgency, or urinary frequency.
C Malaisri et al / J Infect Chemother xxx (2017) 1e7 4
Trang 5Sitafloxacin is active against most bacterial isolates collected
from patients with UTIs The activity of sitafloxacin against
multidrug-resistant (MDR) gram-negative bacteria, such as
ESBL-EC and ESBL-KP, was found to be comparable to or greater than
that of someb-lactam/b-lactamase inhibitors, cephalosporins, or
carbapenems[25] Since sitafloxacin is available in oral
formula-tion, it is a convenient therapy for infections in outpatient settings
as well as hospitalized patients who do not require parenteral
an-tibiotics, and can also be used as a continued therapy after
paren-teral therapy with other antibiotics Although some previous
studies found that carbapenems were superior tofluoroquinolones
in serious infections [32,33], other studies reported equivalent
effectiveness of fluoroquinolones and carbapenems in the
treat-ment of bacteremia caused by ESBL-EC and ESBL-KP[34,35]
The resistance patterns of uropathogens have changed signi
fi-cantly over the past few decades worldwide; the proportion of
ESBL-producing organisms has gradually increased to 17.9e27.7% [36] The 2009e2010 Study for Monitoring Antimicrobial Resis-tance Trends also found that ciprofloxacin and levofloxacin were not effective against ESBL-positive isolates, with only 14.6% and 15.9% susceptible, respectively [36] Several other studies also found high rates of resistance to ciprofloxacin (71e84.8%)[37e39] Thus, the increasing in vitro resistance of ESBL-producing organ-isms tofluoroquinolones has limited the role of these antibiotics In
a study by Tiengrim et al., sitafloxacin demonstrated in vitro activity against 58%e85% of ESBL-EC isolates from Thai patients with UTIs and lower respiratory tract infections[25]
Our study revealed that oral sitafloxacin was clinically and microbiologically effective and well-tolerated in patients with non-bacteremic acute pyelonephritis caused by ESBL-EC The dosage of sitafloxacin (100 mg twice daily) was not therapeutically inferior to that of ertapenem (1 g once daily), given that ESBL-EC was
Table 2
Clinical and bacteriological outcomes of 36 patients at the follow-up visits.
Primary clinical outcomes, n (%)
Secondary clinical outcome, n (%)
Bacteriological outcomes, n (%)
Superinfection at day 10
Positive urine culture at day 30
Median (IQR) white blood cells at day 10, cells/mm 3 7690 (5900e10,010) 8405 (6625e9680) 0.596 Median (IQR) ALT at day 10, U/L 41.0 (36.0e67.0) 39.0 (28.5e56.0) 0.456 ALT, alanine aminotransferase; ESBL-EC, extended-spectrumb-lactamase-producing Escherichia coli; ESBL-KP, extended-spectrumb-lactamase-producing Klebsiella pneu-moniae; IQR, interquartile range.
Table 3
Antibiotic resistance patterns of 36 ESBL-producing E coli isolates.
Antimicrobial drugs Sitafloxacin
n (%)
Ertapenem
n (%)
P value MIC breakpoints (mg/mL) a
Amoxicillin/clavulanic acid 6 (31.6) 6 (35.3) 0.813 8/4 16/8 32/16
Trimethoprim/sulfamethoxazole 14 (73.7) 8 (50.0) 0.149 2/38 4/76
I, indeterminate, R, resistant, S, susceptible.
a Clinical Lab Standards Institute, Performance standards for antimicrobial susceptibility testing; eighteenth informational supplement CLSI document M02-A12 and M07-A10, Wayne, PA: Clinical and Lab Standards Institute, 2016.
b MIC breakpoints 2mg/mL was equivalent to zone diameter breakpoints 16 mm.
c Tigecycline local Product document, rev no.: 4.1 (S22 þ N22): September 07, 2015.
C Malaisri et al / J Infect Chemother xxx (2017) 1e7 5
Trang 6susceptible to sitafloxacin The overall favorable microbiological
response was 84.2% of the patients receiving sitafloxacin and 75.0%
of those receiving ertapenem In this study, the clinical efficacy of
switch therapy from carbapenems to sitafloxacin was comparable
to ertapenem therapy, demonstrating that sitafloxacin is highly
effective as a switch therapy in the management of non-bacteremic
acute pyelonephritis There could be several explanations for this
Firstly, sitafloxacin is a new oral fluoroquinolone with a low MIC
against uropathogens and favorable pharmacokinetics [35]
Sec-ondly, the exclusion criteria of this study eliminated patients with
serious infection (bacteremia and severe sepsis/septic shock)
Finally, the median duration of acute pyelonephritis symptoms was
only 1 or 2 days, which might be classified as early detection of the
disease For these reasons, the clinical cure rate in the current study
was very high
For superinfection, one ESBL-KP was found in the sitafloxacin
group and four Enterococcus spp were found in the ertapenem
group These patients had no symptoms Thus, positive bacterial
growth was asymptomatic bacteriuria This might be because
sitafloxacin was found to be active against 43%e59% of
Entero-coccus spp [25], while ertapenem was not active against
Enterococcus spp
In this study, the overall safety profile and local tolerability of
sitafloxacin were similar to those of ertapenem The most common
sitafloxacin-related AEs previously reported were headache, mild
gastrointestinal symptoms (diarrhea) (17.2%), and mild to moderate
elevation of aminotransferase levels (16.2%) [40] Kawada et al
reported that the proportion of AEs was significantly higher in
patients with complicated UTIs who received sitafloxacin
compared with those who received levofloxacin (24.6% vs 11.6%,
p¼ 0.008)[41] Another study revealed that diarrhea was a more
commonly reported adverse reaction among sitafloxacin recipients
than among those receiving levofloxacin (7.9% vs 4.3%) [42]
However, in our study only one patient in the sitafloxacin group
(5.3%) had diarrhea
The strengths of this study include: its well-defined design;
evaluation of recurrent acute pyelonephritis at approximately 3
weeks after the end of treatment; a high proportion of patient
adherence to medication; and no drop-out patients before the
end of treatment However, this study has some potential
weaknesses that should be taken into consideration Firstly, the
study was only performed at a single center, and local
antimi-crobial susceptibility patterns of ESBL-EC might differ from place
to place Secondly, ultrasonography was not routinely performed
in all patients due to the budget constraints Thus, some patients
might have had complicated pyelonephritis, which could
contribute to unfavorable treatment response Finally, the study
had a limited sample size
In conclusion, our study demonstrated favorable clinical and
microbiological outcomes for sitafloxacin as a switch therapy in the
majority of patients with non-bacteremic acute pyelonephritis
caused by ESBL-EC A treatment regimen of carbapenem followed
by sitafloxacin was effective and well-tolerated among patients
with acute pyelonephritis A large prospective study to determine
the clinical efficacy of sitafloxacin for treatment of ESBL-producing
gram-negative bacterial infections is warranted
Conflict of interest
This study was supported by a grant from Daiichi Sankyo
(Thailand) Ltd This study was designed by the authors Sitafloxacin
was provided by Daiichi Sankyo (Thailand) Ltd, which had no part
in the design or performance of the study, in the data analysis, in
the writing or editing of the manuscript, or in the decision to
submit the manuscript for publication
Acknowledgements
We thank all patients who participated in this study The author would like to thank the staff of the Department of Medicine and Department of Emergency Medicine, Faculty of Medicine Ram-athibodi Hospital, Mahidol University, for taking care of patients
We also would like to thank the staff of Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, for doing bacteria culture and susceptibility testing
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