Activity of Nitrofurantoin Against Urinary Tract Infections (Uti) Isolates of Vancomycin - Resistant Entreococci (Vre)

Full text

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IRANIAN JOURNAL OF PATHOLOGY
Vol.2 No.4, Fall 2007
Original Article
Received: 25 September 2007
Accepted: 2 November 2007
Address communications to: Dr Mohammad Rahbar, Research Center of Reference Laboratories of Iran, Tehran, Iran.
Email: mhhf_rz@yahoo.com
Activity of Nitrofurantoin Against Urinary Tract Infection (UTI)
Isolates of Vancomycin-Resistant Entreococci (VRE):
A Three-Year Survey in an Iranian Hospital
Mohammad Rahbar1, Massoud Hajia1, Mohammad Farzanehkhah1
1. Research Center of Reference Laboratories of Iran, Tehran, Iran
ABSTRACT
Background and Objective: Vancomycin-resistant enterococci (VRE) are major causative agents
of urinary tract infections (UTIs) in hospitalized patients. The aim of this study was to determine
prevalence of UTI caused by VRE in an Iranian 1000-bed hospital and to assess the activity of
commonly used antibiotics including nitrofurantoin against VRE isolates.
Material and Methods: This study was carried out between April 2002 and April 2006 in Milad
Hospital (Tehran). Only patients who had puria and significant bacteriuria included in our study.
All isolates performed identification to species level and susceptibility testing performed by disk
diffusion method as recommended by Clinical Laboratory Institute Standards (CLSI).
Results: In total, 837 enterococcus species were isolated from UTIs that 668 (79.8%) and 169
(20.2%) isolates were E. faecalis and E. faecium respectively. Analysis of the collected data revealed
that 9.43% of vancomycin-resistant strains were resistant to nitrofurantoin as well (6 out of 65),
while 84.9% of the isolated enterococci (54 out of 65) were vancomycin-resistant and nitrofurantoin-
sensitive. The obtained data also showed that both vancomycin- and nitrofurantoin-resistant isolates
had higher frequency rate in admitted patients compared with out-patients.
Conclusion: It is concluded that susceptibility of approximately 85% of VRE to nitrofurantoin
indicates that this antibiotic still is the suitable alternative drug for treatment of urinary tract
infections caused by VRE.
Key words: Nitrofurantoin, Vancomycin, Resistance, Enterococcus, Urinary tract infection
Iranian Journal of Pathology (2007)2 (4), 171 -174
Introduction
Urinary tract infections (UTIs) are one of the
most common bacterial infections in humans
both in community and hospital settings (1). In almost
all cases there is a need to start treatment before the
final microbiological results available (2). Area-
specific monitoring studies aimed to gain knowledge
about the type of pathogens responsible for UTIs and
their resistance patterns may help the clinicians to
choose the right empirical treatment (3).
Enterococci are constitutive member of the intestinal
flora of humans and animals and may also colonize
the upper respiratory tract, biliary tracts and vagina
of otherwise healthy persons. Enterococci have been
documented to cause infection of the urinary tract and

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other sites (4). Although more than one dozen species
of enterococcus have been recognized, Enterococcus
faecalis and Enterococcus faecium accounts for
approximately 85-90% and 5-10% of human
enterococcal infections respectively. Vancomycin-
resistant enterococci, especially E. faecium is
prevalent in the hospitalized patients. Management
of VRE infections is a clinical challenge as these
organisms may be resistant to several antibiotics with
unique action (5). Recent studies have demonstrated
that nitrofurantoin is active against urine isolates of
VRE (1).
Therefore, the purpose of this study was to determine
prevalence of UTI caused by VRE in a 1000-bed
hospital in Tehran and to assess the activity of
commonly used antibiotics, especially nitrofurantoin
against urinary isolates of VRE.
Material and Methods
Study Period
This study was carried out between April 2002
and April 2006 in Milad Hospital. Milad Hospital is
a 1000-bed non-teaching and the largest hospital in
Tehran. Patients were from varying ethnical kinds,
local patients, or referred from elsewhere.
Specimens
Only patients who had puria and significant
bacteriuria obtained included in the microbiological
analysis. In total, 837 enterococcal strains were
isolated from patients. Only one specimen for
each patient was accepted and duplicated isolates
excluded.
Antibiotic susceptibility Testing
All isolates performed identification to species level
and susceptibility testing performed by disk diffusion
method as recommended by Clinical Laboratory
Standards Institute (CLSI) (6).
Quality Control and Standard Species
For the quality control of susceptibility testes,
Escherichia coli ATCC 25922, Staphylococcus
aureus ATCC29213, Enterococcus faecalis ATCC
29212 and Pseudomonas aeruginosa ATCC27853
strains were used.
Applied Antibiotics for evaluating isolated specimens
All urine isolates were tested for resistance against
ampicillin, penicillin, ciprofloxacin, erythromycin,
tetracycline, norfloxacine, nitrofurantoin, and
vancomycin.
Results
In total, 837 enterococcus species were isolated from
UTI infections. Sensitivity of all of these isolates was
evaluated against commonly used antibiotics (Table
1). The lowest resistance rate was for vancomycin
and nitrofurantoin (Fig. 1 and Table 2).
Analysis of the collected data revealed that 9.43%
of vancomycin- resistant strains were also resistant
to nitrofurantoin as well (6 out of 65), while 84.9%
of the isolated enterococci (54 out of 65) were
vancomycin-resistant and nitrofurantoin-sensitive
(Tables 2-3). In addition, 169 out of 837 isolated
enterococci
were E. faecium and the remaining 668
isolated organisms were identified as E. faecalis.
On the basis of analyzed data, 9 out of 54 identified
vancomycin-resistant strains, nitrofuranoin-sensitive
were E. faecalis and 45 were E. faecium (Table 3).
Meanwhile, the obtained data also showed that both
vancomycin- and nitrofurantoin-resistant isolates have
higher frequency rate in admitted patients compared
with out-patients (Table 4).
Discussion
Enterococci has been recognized as the second
pathogenic agent of UTI (3,7). Vancomycin-
resistant entrococci (VRE) has higher mortality
rate than vancomycin-sensitive enterococci (VSE)
(8). Enterococci can also cause peritonitis, pelvic
abcesses, and surgical site infections. Unfortunately,
the rate of VRE has increased in recent years.
Therefore, early diagnosis of VRE isolates is very
important among nosocomial infection, specially
those VRE strains containing Van B gene. These
strains show intermediate or low level of resistance
causing difficulty in diagnosis (9,10).
Antibiogram sensitivity test showed vancomycin
and nitroforantoin had the lowest resistant rate in
comparison with other applied antibiotics among
isolated entrococci from UTI. Resistant rate was 65
(7.76%) and 58 (6.92%) out of 837 for vancomycin
and nitroforantoin in the isolated enteroccoci
respectively.
Very few studies in our country have described the
epidemiology and clinical importance of VRE in urine
isolates. Previous studies in Tehran have showed that
nearly 7% of urine isolates of enteerococci are VRE
which resembles our study (11,12).
Reported resistances rates to nitrofurantoin are
lower in other studies in comparison with our research
(1,13). We had 58 nitrofurantoin-resistant enterococci
Activity of Nitrofurantoin Against Urinary Tract Infection (UTI) Isolates of Vancomycin-Resistant Entreococci (VRE)...

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Vol.2 No.4, Fall 2007
Mitra Mehrazama, et al
that just 6 cases were resistant to vancomycin too.
The rate of vancomycin- and nitrofurantoin-resistant
isolated enterococci is similar to Zanel’s report (0.6%)
(5), the total nitrofurantoin cases were higher in this
study than other reports, meaning the lack of proper
treatment strategy in the nosocomial enterococci
infections therapy. Analysis of the results also
revealed that the frequency of E. faecalis is similar to
other reports (14). Resistance rate to vancomycin is
higher in E. faecium than E. faecalis in spite of higher
isolation rate of E. faecalis (79.81%) than E. faecium.
Meanwhile, 12 out of 668 E. faecalis were resistant
to vancomycin (1.79%) while resistance rate for E.
faecium were 53 out of 169 for E. faecium (31.36%).
These results are in agreement with Zhanel` report
(1,5). Resistance rate for nitrofurantoin is different
than vancomycin in these two species. In this respect,
24 out of 169 (14.2%) were resistant to E. faecium
while it was 34 out of 668 (5.08%) for E. faecalis.
Conclusion
Our study demonstrated that nitrofurantoin is more
active against E. faecium and E. faecalis in comparison
to other routinely-used antibiotics for treatment
of UTIs caused by enterococci. More importantly,
nitrofurantoin has retained its activity against VRE
isolates. Our in vitro data are consistent with the very
limited clinical studies that suggest that nitrofurantoin
may be effective in the treatment of VRE infections
associated with the urinary tract.
Table 1. Sensitivity rate of enterococcal isolates to applied antibiotics
Ampicillin Penicillin Ciprofloxacin Norfloxacin Erytromycin Tertacycline Vancomycin Nitrofurantoin
E.faecalis
E.faecium
E.faecalis
E.faecium
E.faecalis
E.faecium
E.faecalis
E.faecium
E.faecalis
E.faecium
E.faecalis
E.faecium
E.faecalis
E.faecium
E.faecalis
E.faecium
Sensitive 553 38 30 13 223 24 246 53 120 34 24 82 650 120 648 129
Intermediate - 1 9 7 9 - 2 2
Resistant 115 130 638 156 445 136 422 116 548 128 644 78 18 47 20 38
Total 668 169 668 169 668 169 668 169 668 169 668 169 668 169 668 169
Table 2. Sensitivity rate of entrococcus isolates to vancomycin and nitrofurantoin
Resistant Intermediate Sensitive Total
Vancomycin 65 2 768 837
Nitrofurantoin 58 36 741 837
Table 3. Comparison of sensitivity rate for vancomycin and nitrofurantoin
Nitrofurantoin
resistant isolates
Nitrofurantoin
intermediate isolates
Nitrofurantoin sensitive isolates
E.faecium E.faeculis
Total
Vancomycin resistant isolates 6 5 45 9 65
Vancomycin intermediate isolates -- -- 2
Vancomycin sensitive isolates 52 31 84 601 768
Table 4. Comparison of the vancomycin- and nitrofurantoin-resistant isolates in admitted patients
and out-patients
Out-patient In-patients Total
Vancomycin-resistant 10 55 65
Nitrofurantoin-resistant 14 44 58

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Figure 1. Sensitivity rate of enterococcal
isolates to applied antibiotics
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