Content uploaded by Tritan Kalo
Author content
All content in this area was uploaded by Tritan Kalo on May 09, 2017
Content may be subject to copyright.
Original Report
Therapeutic Efficacy of Perfloxacin in Treatment of
Ampicillin-Resistant mphoid Fever in 7 Days versus
10
Days
Tristan Kale, MD;* Farzin Davachi, MD;? Aferdita Nushi, MD;* Sabahet Dedja, MD;*
Luljeta Karapici, MD;* Najada Corno, MD;* and Dhimiter Kraja, MD*
ABSTRACT
Objective: Typhoid fever is endemic in Albania and is becom-
ing increasingly resistant to ampicillin, chloramphenicol, and
trimethoprim-sulfamethoxazole. Perfloxacin has been shown
to have significant activity in vitro against Salmonella species.
The authors studied its therapeutic efficacy in patients with
typhoid fever.
Methods: Thirty patients with ampicillin-resistant typhoid fever,
who were admitted to the Infectious Disease Clinic at the Uni-
versity Hospital Center of Tirana, were enrolled in this prospec-
tive, nonblinded clinical trial. Patients were treated with oral
perfloxacin at 400 mg twice daily. They were randomized to
receive treatment for either 7 days (group I) or 10 days (group II).
Conclusions: Excellent therapeutic responses were observed in
all patients in both groups. In every case, there was significant
clinical improvement with defervescence and sterile blood cul-
tures by day 4 and three consecutive negative urine and stool
cultures at the end of treatment. Perfloxacin was highly effec-
tive in treatment of typhoid fever. Treatment for 7 days appeared
to be as effective as treatment for IO days. In both groups, bile
cultures at the end of treatment and at 2 months follow-up
were sterile, suggesting that both regimens were effective in
preventing a chronic carrier state.
Key Words: Albania, antimicrobial .susceptibilitL: perfloxacin,
Salmonella typhi, typhoid fever
Int J Infect Dis 1997; 2:12-14.
Typhoid fever is endemic in Albania, at times reaching
epidemic proportions. Salmonella typhi bacilli are
becoming increasingly resistant to ampicillin, chloram-
phenicol, and sulfamethoxazole.The resistant strains cause
*Department of Infectious Diseases, University Hospital Center of Tirana,
AIbania; +Department of Pediatrics, NewYork Medical CoIlege,VaIhalla,
NewYork; and *Department of Clinical Microbiology, University Hospital
Center of Tirana, Albania.
Received: October 10,1996; Accepted: April 16,1997.
Address correspondence to Dr. E Davachi, K.l? 1731,Tirana,Albania.
12
more serious clinical complications and may lead to a
chronic carrier state. Because of the high incidence of
resistant strains, there is an urgent need for alternative
therapies for typhoid fever.The newer quinolones have
been shown to have significant in vitro activity against
Salmonella species as well as other enteric pathogens.
Perfloxacin has bacteriologic and pharmacokinetic prop-
erties that make it particularly promising for the treat-
ment of these infections.lW3 In cases of typhoid fever, 7
days of treatment with perfloxacin has been reported to
be as effective as 10 days.*
To evaluate the effectiveness of oral perfloxacin in
the treatment of typhoid fever due to multiresistant
strains of S. typhi, a prospective study was done at the
Department of Infectious Diseases at the University Hos-
pital Center of Tirana.The purposes of the study were to
evaluate the effectiveness of oral perfloxacin in the treat-
ment of infections due to ampicillin-resistant strains of S.
typhi, to study its efficacy in prevention of a chronic car-
rier state, and to compare outcomes after treatment for
7 or 10 days.
METHODS
Patients were eligible for this study if they had a positive
blood culture due to an ampicillin-resistant strain of S.
typhi, had signs and symptoms of typhoid fever, and had
not received quinolones in the 2 weeks prior to hospi-
talization.Treatment was considered successful if all of the
following cultures were negative for S. typhi: a blood cul-
ture during treatment, urine and stool cultures on 3 con-
secutive days following treatment, and bile cultures at
the end of treatment and at 2-month follow-up.
Thirty patients, examined between May 1992 and
February 1994, met the eligibility criteria listed above
and were enrolled. There were 18 males (60%) and 12
females (40%); their ages ranged from I6 to 42 years
(mean, 24 y).The patients were divided into two groups
of 15. Group I received oral perfloxacin at 400 mg twice
daily for 7 days, and group II received the same regimen
for 10 days. Patients were evaluated by interview, physi-
cal examination, and laboratory testing of blood, urine,
stool, and bile samples.
Perfloxacin Treatment of Typhoid Fever /
Kalo et al
13
Table 1. Clinical Findings, at Admission, of the 30 Patients with
Typhoid Fever
Symptoms
Fever
Headache
Splenomegaly
Hepatomegaly
Anorexia
Chills
Diarrhea
Constipation
Abdominal pains
Rose spots
Nausea or vomiting
Cough
Rales
Cervical adenopathy
Neurologic manifestations
Dysuria
Group I
n = 15 (100%)
15 (100)
12 (80)
11 (73)
11 (73)
Q (60)
7 (47)
7 (47)
7 (47)
6 (40)
6 (40)
5 (33)
3 (20)
3 (20)
2 (13)
2 (13)
2 (13)
Group II
n = 75 (100%)
15 (100)
14 (93)
12 (80)
10 (67)
7 (47)
Q
(60)
9
(60)
6 (40)
7 (47)
7 (47)
6 (40)
3 (20)
3 (20)
3 (20)
3 (20)
2 (13)
RESULTS
The clinical findings in the 30 patients are summarized
in Table 1. On admission, all of the 30 patients had blood
cultures that were positive for S. typhi; only 11 (36%)
had positive urine cultures. Table 2 summarizes the
antimicrobial susceptibilities of the blood culture iso-
latesAl of the blood culture strains were sensitive to per-
floxacin and resistant to ampicillin, 25 strains (83%) were
resistant to ampicillin and chloramphenicol, 21 strains
(70%) were resistant to ampicillin and trimethoprim-sul-
famethoxazole, and 12 strains (40%) were resistant to
ampicillin, chloramphenicol, and trimethoprim-sul-
famethoxazole.
Defervescence began on the second day in ten
patients (67%) and on the third day in the remaining five
cases in each group. All patients, in both groups, were
afebrile by day 5. Blood cultures were sterile by day 3 in
ten patients (67%) in each group, and in all patients by
day 4.All stool cultures were negative by the third day of
treatment.
Stool and urine cultures for S. typhi were done on
days 7,8, and 9 for group I and on days 10, 11, and 12
for group II; all of these cultures were negative. Bile cul-
tures, performed at completion of treatment and at the
2-month follow-up, were negative for all patients in both
groups. No relapses occurred during hospitalization or
during the subsequent 2 months.
Treatment with perfloxacin resulted in nausea or
abdominal discomfort in four patients (13%); however, it
was not severe enough to warrant discontinuation of the
drug. Other adverse reactions, such as rash, headache,
fatigue, insomnia, or diarrhea were not observed. No alter-
ations of hematologic or biochemical test results were
seen that could be attributed to perfloxacin.
DISCUSSION
Because of the emergence of strains of S.
@phi
that
are
resistant to ampicillin, patients with typhoid fever are at
risk of serious clinical complications if they do not
receive appropriate therapies. The complications may
include enteric hemorrhage, perforation, pneumonia,
myocarditis, meningitis, cholecystitis, hepatic or splenic
abscesses, phlebitis, spondylitis, spondylodiskitis,
pyomyositis, and acute rhabdomyolysis.5,6
In this study, patients with typhoid fever due to ampi-
cillin-resistant strains of S.
@phi
were treated with a 7- or
lo-day course of oral perfloxacin at 400 mg twice daily.
There was an excellent clinical and microbiologic
response to both regimens. With treatment durations of
either 7 or 10 days, there was significant clinical improve-
ment with defervescence and sterile blood cultures by
day 4, three consecutive negative urine and stool cultures
at the end of treatment, and negative bile cultures at the
end of treatment and 2 months later. The 7- and 1 O-day
regimens were equally safe and effective both in treat-
ment of the acute illness and in prevention of a chronic
carrier state.
Fluoroquinolones are effective against enteric
pathogens such as
Salmonella
species,
Shigella
species,
and
Yersinia
species.They have several advantages over
nalidixic acid, the parent compound of this class of
antimicrobial agents; these include enhanced bioavail-
ability with oral administration, reduced protein bind-
ing, and longer serum half-lives. Because of these
characteristics, lower and more infrequent doses can be
given.
The fluoroquinolones also have the advantage of
being concentrated within phagocytes and other intra-
cellular sites favored by pathogens such as
Salmonella
species; the intracellular concentration of peffloxacin may
be 1.8 to 14 times the serum level.4,7-10This characteristic
Table 2. Results of Antimicrobial Susceptibility Testing of Isolates of Salmonella typhi from Blood Cultures of 30
Patients with Typhoid Fever
Antibiotic Number Resistant (%)
Ampicillin
Ampicillin + chloramphenicol
Ampicillin + trimethoprim-sulfamethoxazole
Ampicillin + chloramphenicol + trimethoprim-sulfamethoxazole
Perfloxacin
30 (100)
25 (83)
21 (70)
12 (40)
0 (0)
14 International Journal of Infectious Diseases
/ Volume 2, Number 1, July 1997
may be critical for eradication of an enteric pathogen
from intracellular sites within the intestinal or biliary
tracts.l’
CONCLUSION
Perfloxacin, because it is well tolerated, has significant
pharmacokinetic advantages, and is highly effective in
this indication, should be considered for use in cases of
ampicillin-resistant typhoid fever.Treatment with 400 mg
twice daily for 7 days appears to be safe and effective
for typhoid fever.This regimen produced prompt relief
from the acute symptoms of the infection and seemed to
reduce the risk of its recurrence.
ACKNOWLEDGMENTS
The authors thank Nancy Davachi for her help in preparing
this manuscript.
REFERENCES
1, Keusch G’IXntimicrobial therapy for enteric infections and
typhoid fever: state of the art. Rev Infect Dis 1988; lO(Supp1
1):199-205.
2. Bryan JP, Rocha H, Scheld W. Problems in salmonellosis:
rationale for clinical trials with new p-lactam agents and
quinolones. Rev Infect Dis 1986; 8:189-207.
3. DuPont HL, Ericsson CD, Robinson A, et al. Current problems
in antimicrobial therapy for bacterial enteric infection. Am
J Med 1987; 82(Suppl4A):324-328.
4. Ait-Khaled A, Zidane L. A seven-day perfloxacin course for
the treatment of typhoid fever in Algeria [Abstract 1931. Sec-
ond International Symposium on New Quinolones, Geneva,
Switzerland,August 1988.
5. Hdok WE. Salmonella species (including typhoid fever). In:
Mandell, Douglas, Bennett, eds. Principles and practice of
infectious diseases. 2nd Ed. NewYork: John Wiley and Sons,
1985:1256-1268.
6. Kalo T, Feyzo E, Begari N. Rhabdomyolysis, a real complica-
tion of typhoid fever.Acta Cardiomyologia 1993; 5:85-91.
7. Hajji M, El Mdaghri N, Benbachir M. Prospective random-
ized comparative trial of perfloxacin versus cotrimoxazole
in the treatment of typhoid fever in adults. Eur J Clin Micro-
biol Infect Dis 1988; 7:361-363.
8. Walker R, Wright AJ. The quinolones. Mayo Clin Proc 1987;
62:1007-1012.
9. Wolfson JS, Hopper DC. Fluoroquinolone antimicrobial
agents. Clin Microbial Rev 1989; 4:378-424.
10. Raymond J, Moulin l$ Badoual J, Gengrel D. Eradication of
convalescent phase Salmonella carriage with two oral doses
of perfloxacin. Eur J Clin Microbial Infect Dis 1994; 13:
304-307.
11. Asperilla MO, Smego RA, Kieth SL. Quinolone antibiotics in
the treatment of Salmonella infections. Rev Infect Dis 1990;
12:873-889.
