Jordan Journal of Pharmaceutical Sciences, Volume 3, No.

2, 2010

Comparative Study on Resistance Pattern of Different Pathogens Against

Cefixime and Cefepime

Ale-Zehra1 , Baquir Shyum Naqvi2, Rabia Bushra2 and Syeda Qadam Ali3
1
Aga Khan University Hospital, Karachi, Pakistan.
2
Ziauddin College of Pharmacy, Ziauddin University.
3
Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi.

ABSTRACT
Irrational use of antibiotics has fueled a major increase in prevalence of multi drug resistant pathogens, leading
some to speculate that we are nearing the end of antibiotic era. The assessment of the activity of an antibiotic is
crucial to the successful outcome of antimicrobial therapy. The objective of the study is to evaluate the resistance
pattern between cefixime (a third generation cephalosporin) of 5µg and cefepime (a fourth generation
cephalosporin) of 30µg, on a total of 138 different clinical isolates namely as; Escherichia coli (30%),
Staphylococcus aureus (30%), Salmonella typhi (14%), Klebsiella pneumoniae (13%) and Pseudomonas
aeruginosa (13%). The isolates were collected over a period of one year (January 2008 to January 2009) from
pathological laboratories of different hospitals in Karachi, Pakistan, which comprised of 59 urine, 30 skin pus,
29 ear pus, 15 blood and 5 stool samples. In-vitro antibiotic sensitivity was performed by disk diffusion or
Bauer-Kirby method using 0.5 McFarland standard. Cefepime showed good sensitivity of about 92.6% against
Escherichia coli, 85% against Staphylococcus aureus, 94% against Klebsiella pneumoniae, 77.77% against
Pseudomonas aeruginosa and 65% against Salmonella typhi. Cefixime showed least sensitivity against
Pseudomonas aeruginosa (16.66%) and maximum effectiveness against Salmonella typhi (90%). Results of the
study indicate that cefepime is more effective for the treatment of infections caused by the above pathogens
except for Salmonella typhi. It is concluded that in the face of continuing development of resistance,
considerable effort will be required to maintain the effectiveness of these drug groups.
Keywords: Cefixime, Cefepime, Disk Diffusion Method, Microbial Resistance, Pathogens.

INTRODUCTION sensitiveness of the pathogen before treatment can be started

(2). Surveys of antibiotic use, have demonstrated that more
The early treatment failures with antibiotics did not than 50% of antibiotic prescribing can be inappropriate; in
represent a significant problem since other antimicrobial situations where they are either ineffective (viral infections)
classes were available. It is the emergence of multiple or the selected agent, dose and duration of use are
resistances that is causing major problems in the clinic today inappropriate (3).
(1). Different microbial species and stains have different A number of effective antimicrobial agents such as, β-
degree of susceptibility to different chemotherapeutic agents. lactams, aminoglycosides, fluroquinolines, tetracyclines,
The susceptibility can change with time, even during therapy and trimethoprim/sulfamethaxazole are available. But
with a specific drug, thus the physician must know the cephalosporins are currently among the most widely
prescribed class of antibiotics in hospitals The number of
Received on 14/10/2009 and Accepted for Publication on 2nd, 3rd and even 4th generation cephalosporins has
30/3/2010. proliferated in recent years, there are now more than 30
E-mail: ale-zehra@hotmail.com.

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Comparative Study… Ale-Zehra, Baquir Shyum Naqvi, Rabia Bushra and Syeda Qadam Ali

versions. Each generation has a broader spectrum of Escherichia coli and multiple drug resistant Streptococcus
activity than the previous one (2, 4). Because of pneumoniae, Enterobacter sp. It is administered either
similarities in their beta-lactam ring structures, cross- intravenously or intramuscularly and exhibits linear
react with penicillins and therefore should not be given to pharmacokinetics. The drug is distributed widely, and
patients known to be penicillin allergic. Despite the fact, 20% is protein bound. The elimination half-life in adults
a patient allergic to penicillin has only about a 10% is approximately 2 hours, and in children, it is slightly
chance of being hypersensitive to cephalosporins also (5). less (1.7 hours) (12, 13). It represents an important
Cefixime is a semi synthetic, broad spectrum, third therapeutic option for the empiric treatment of bacterial
generation cephalosporin, similar to penicillins chemically in meningitis in children, based on the good clinical
mechanism of action and toxicity but more stable than response and bacteriologic eradication rates (14).
penicillins to many bacterial beta-lactamases. In vitro tests The aim of study is to assess in vitro susceptibility of
and clinical trials have indicated that most strains of the different microorganisms against these two broad
following organisms can be effectively eradicated by using spectrum cephalosporins (cefixime and cefepime) in local
adequate doses of cefixime .Streptococcus pneumoniae, population of Karachi, Pakistan, using disk diffusion
Streptococcus pyogenes, Haemophilus influenzae (beta- method for surveillance of emerging antimicrobial
lactamase positive and negative), Moraxella catarrhalis resistance.
(formerly Branhamella catarrhalis), Escherichia coli,
Proteus mirabilis, and Neisseria gonorrheae (beta- MATERIAL AND METHODS:
lactamase positive and negative) (6). It is administered orally Collection of Clinical Isolates
in children and adults, once or twice daily with good A total of 138 different clinical isolates including both
antimicrobial activity against Salmonella typhi. Due the Gram –ve and Gram +ve pathogens were collected over a
emergence of MDR S. typhi in endemic countries, period of one year (January 2008 to January 2009) from
alternative drugs for the treatment of typhoid fever are different pathological laboratories (Ehsanullah laboratory,
required. Santillán et al., in 2000 conducted a study to assess Laboratory of Liaquat College of medicine and dentistry and
the efficacy of cefixime in the treatment of typhoid fever, Dar-ul- Sehat hospital and Agha khan university hospital)
and observed all strains included in the experiment were located in Karachi, Pakistan. These pathogens were isolated
sensitive to cefixime (7). Cefixime is a safe, effective, and from urine, stool, blood, and pus (skin and ear) samples. The
cheaper oral option for the treatment of multidrug-resistant percentages of clinical isolates used in this study were: 30%
enteric fever (8). Escherichia coli, 30% Staphylococcus aureus, 14%
Cefepime is a 4th generation, broad-spectrum Salmonella typhi, 13% Klebsiella pneumoniae and 13%
cephalosporin, with a higher degree of activity against Pseudomonas aeruginosa.
both Gram-positive and Gram-negative bacteria.
Cefepime is currently widely used in hospitals, for its Method and Break Points
approved indications, including empirical monotherapy Antimicrobial susceptibility test was carried out using
for febrile neutropenia, pneumonia, bacteraemia, and the disk diffusion technique (Bauer- Kirby susceptibility
urinary tract, abdominal, and skin or soft-tissue infections test) as described by the National Committee for Clinical
(9). Cefepime’s superior activity is attributed to more Laboratory Standards (NCCLS) (15). The antimicrobial
rapid penetration into bacteria, the targeting of multiple disks contained Cefixime 5µg (CFM 5, Lot No. 622076,
penicillin-binding proteins, or lower affinity for several expiry date 2011 Jan.) and Cefepime 30µg (FEP 30, Lot
β-lactamases (10, 11). It possesses good activity against No. 627226, expiry date 2011), obtained from Oxoid Ltd;
pathogens including Pseudomonas aeruginosa, Klebsiella (Basingstoke, Hampshire, England). Zone diameter
pneumoniae, Proteus mirabilis, Staphylococcus aureus, breakpoints for susceptible and resistant isolates were set

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as 14 mm (resistant), 15-17mm (intermediate) and regarded as indicative of non useful therapeutic options
18mm (susceptible) for cefixime and 16 mm (resistant), similar to the resistant category for treatment purposes (16).
17-19mm (intermediate) and 20mm (susceptible) for RESULTS AND DISCUSSION:
cefepime(15). As antibiotic resistance reduces treatment efficacy, it
Selection and Preparation of Media is a time to consider routine susceptibility testing to guide
Mueller-Hinton Agar (Oxoid Ltd; Basingstoke, individual patient treatment and surveillance of antibiotic
Hampshire, England) was prepared according to the resistance (17). An extensive work has been reported by
manufacturer’s guide lines and sterilized by autoclaving many authors on microbial drug resistance (18- 22).
(121 ◦C for 15 min). Plates were prepared by pouring freshly Among different in vitro methods, disk diffusion method
prepared, sterilized and cooled agar into flat glass petri has been utilized as a major technique for evaluation of
dishes (90mm) to a uniform depth of approximately 4mm. microbial resistance and susceptibility against antibiotics
(23-26).
McFarland Turbidity Standard and Preparation of Orally administered cephalosporins, such as cefixime,
Inoculum possess good activity and attains serum concentrations
McFarland No. 0.5 standard was prepared (by adding above the MICs for most Enterobacteriaceae (27, 28). In this
0.5 ml of 0.048 M barium chloride to 99.5 ml of 0.36N study, cefixime showed good activity against E. coli, S
sulfuric acid). With a sterile polyester swab, 4 -5 similar .aureus, and K. pneumoniae. E. coli and K. pneumoniae
appearing colonies (which were well isolated on primary were isolated from urine samples and S.aureus from skin
medium), were transferred to 3 ml trypticase soy broth. and ear pus cultures of different individuals. It possessed
The culture tube was incubated at 37◦C, for 2 to 6 hours superior activity against S. typhi (90%). Out of 20 samples
to produce the bacterial suspension turbidity similar to only two specimens showed resistance against cefixime.
McFarland No. 0.5 standard. These two resistant pathogens were separated from the same
Inoculation source that is blood, but from two different individuals. This
Plates were inoculated within 15 minutes of variation in the zones may because that these two
preparation of suspension; a dry sterile polyester swab individuals had already been exposed to the same antibiotic
was immersed in bacterial suspension and streaked in many times in the past, either rationally, inappropriately or
three directions at approximately 60◦angle. Antimicrobial self medicated, and so resulted in the resistance. The higher
disks were placed using sterile forceps to a suitable activity gives an idea that cefixime may be a drug of choice
distance to avoid overlapping of zones of inhibition. The in the treatment of typhoid fever. Matsumoto et al., in 1999
plates were incubated at 35◦C for 16-18 hours. carried out the study for cefixime against 73 clinical isolates
of S. typhi; it exhibited excellent activity against reflecting
Interpretation its high beta-lactamase stability (29). Increasing prevalence
After that period, the zone appeared around the disks of multidrug-resistant (MDR) S. typhi strains in typhoid
was measured, including the diameter of disk (6mm) using fever has been reported. Oral cefixime therapy given as a 12-
sliding calipers held on the back of the inverted Petri plate to day regimen (20-30 mg/kg divided twice daily)
the nearest millimeter. Each zone was compared with demonstrated both safety and efficacy and it is most cost
known standards (15), and the organisms under test were effective therapy (30). Cefixime did not show an excellent
identified as susceptible or resistant to that particular response against P. aeruginosa isolates, out of 18 only 3
antibiotic (Table I). Pathogens that showed zones in the samples were susceptible to cefixime. From these three
range of intermediate resistance (IR) are not considered as susceptible organisms, two were cultured from ear pus of
sensitive or susceptible organisms against the tested unlike individuals, and one from skin pus. There are few
antibiotic. The result values ranges in this are usually factors that contribute in variation of resistant range among

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individuals. Some of the bacteria acquired in the community still effective against Klebsiella (77.77%) and possesses
are antibiotic resistant and have been carried into the strong activity against S. typhi (90%).
community by people returning from hospital where Cefepime is relatively a new cephalosporin and shows
antibiotic resistant bacteria are more common. Other factors much less resistance than cefixime. Cefepime is sensitive
driving towards the emergence and spread of antibiotic against all the tested microorganisms, 92.6% against E.
resistant bacteria as well as the spread of other bacteria in the coli, 85% against S. aureus, 65% against S. typhi, 94%
community are improper food preparations practices both in against K. pneumonia, and 77.7% against P.aeruginosa,
home and commercial establishments, inadequate water used in this work. Cefepime is not as much effective
treatments and inspection, and poor sanitation and hygiene against S. typhi as cefixime. Cefepime is considered as
(31). Results of study illustrate the development of highly potent agent against E. coli and K. pneumoniae
resistance in P.aeruginosa against the broad spectrum specifically. Only 3 isolates out of 41 E.coli (all three
cefixime. Majority of S. aureus isolates were resistant to isolated from urine samples) and 1 out of 18 K.
cefixime, 15 isolates from 41 were sensitive, thus giving pneumoniae (isolated from urine) did not show sensitive
63.4% resistance. It is evident from results that cefixime is zones (Table 1).

Table 1: Resistance Pattern of CEFEPIME (30µg) and CEFIXME (5µg) Against Different Pathogens
CEFIXME Pathogen Shows Pathogen Shows
Cefepime
(5µg) Resistance/Sensitivity Resistance/Sensitivity
No. of (30µg)
Zone of Intermediate Intermediate
Clinical SOURCES Resistant Sensitive Zone of Resistant Sensitive
inhibition Resistant Resistant
isolates (R)* (S)*** inhibition (R)* (S)***
(mm) (IR)** (IR)**
≤14mm ≥18mm (mm) ≤16mm ≥20m
15-17 mm 17-19mm
Escherichia coli
1 URINE NIL R 11.2 R
2 URINE 22 S 19 S
3 URINE 21 S 20 S
4 URINE NIL R 21 S
5 URINE 20 S 21 S
6 URINE 21 S 19 S
7 URINE 19 S 20 S
8 URINE 21 S 17 IR
9 URINE 21 S 23 S
10 URINE 18 S NIL R
11 URINE 22.5 S 23.5 S
12 URINE 18 S 22 S
13 URINE 19 S 23 S
14 URINE 12 R 20 S
15 URINE 20 S 20 S
16 URINE 24 S 21 S
17 URINE NIL R 19 S
18 URINE 20 S 21 S

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CEFIXME Pathogen Shows Pathogen Shows

Cefepime
(5µg) Resistance/Sensitivity Resistance/Sensitivity
No. of (30µg)
Zone of Intermediate Intermediate
Clinical SOURCES Resistant Sensitive Zone of Resistant Sensitive
inhibition Resistant Resistant
isolates (R)* (S)*** inhibition (R)* (S)***
(mm) (IR)** (IR)**
≤14mm ≥18mm (mm) ≤16mm ≥20m
15-17 mm 17-19mm
19 URINE 16 IR 22 S
20 URINE 21 S 23 S
21 URINE 22 S 20 S
22 URINE 21 S 14 R
23 URINE 23 S 23 S
24 URINE 21 S 19 S
25 URINE 16 IR 22 S
26 URINE 22 S 24 S
27 URINE 20 S 24 S
28 URINE 19 S 24 S
29 URINE NIL R 25 S
30 URINE 16 IR 21.8 S
31 URINE 12 R 22 S
32 URINE 15 IR 22.5 S
33 URINE NIL R 22 S
34 URINE NIL R 23.5 S
35 URINE 12 R 21 S
36 URINE 19 S 31 S
37 URINE 15 IR 26 S
38 URINE 23 S 22 S
39 URINE 21 S 20 S
40 URINE 20 S 21 S
41 URINE 22 S 22 S
Staphylococcus aureus
42 SKIN PUS NIL R 22 S
43 SKIN PUS 19 S 29 S
44 SKIN PUS 9 R 22 S
45 SKIN PUS NIL R 29 S
46 SKIN PUS NIL R 27 S
47 SKIN PUS 22 S 24.5 S
48 SKIN PUS 12 R 21 S
49 SKIN PUS NIL R NIL R
50 SKIN PUS 10 R 23 S
51 SKIN PUS 21 S 24 S

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CEFIXME Pathogen Shows Pathogen Shows

Cefepime
(5µg) Resistance/Sensitivity Resistance/Sensitivity
No. of (30µg)
Zone of Intermediate Intermediate
Clinical SOURCES Resistant Sensitive Zone of Resistant Sensitive
inhibition Resistant Resistant
isolates (R)* (S)*** inhibition (R)* (S)***
(mm) (IR)** (IR)**
≤14mm ≥18mm (mm) ≤16mm ≥20m
15-17 mm 17-19mm
52 SKIN PUS 18 S 19 IS
53 SKIN PUS NIL R NIL R
54 SKIN PUS 20 S 18 IS
55 SKIN PUS 13 R 19 IS
56 SKIN PUS 8 R 20 S
57 SKIN PUS 19 S 20 S
58 SKIN PUS NIL R NIL R
59 SKIN PUS 16 IR 23 S
60 SKIN PUS 20 S 19 IS
61 SKIN PUS 7 R 19 IS
62 SKIN PUS 22 S NIL R
63 SKIN PUS 7 R 23 S
64 SKIN PUS 15 IR 22 S
65 SKIN PUS 21 S 22 S
66 SKIN PUS 10 R 25 S
67 SKIN PUS 22 S 32 S
68 EAR PUS 20 S 33 S
69 EAR PUS NIL R 31 S
70 EAR PUS 21 S NIL R
71 EAR PUS NIL R 20 S
72 EAR PUS 19 S NIL R
73 EAR PUS NIL R 23 S
74 EAR PUS 19 S 32 S
75 EAR PUS NIL R 22 S
76 EAR PUS 18 S 23 S
77 EAR PUS 15 IR 23 S
78 EAR PUS 14 R 26 S
79 EAR PUS 22 S 21 S
80 EAR PUS 9 R 19 IS
81 EAR PUS 15 IR 21 S
82 EAR PUS 10 R 22 S
Klebsiella pneumoniae
83 URINE 23 S 16 R
84 URINE 12 R 21 S

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CEFIXME Pathogen Shows Pathogen Shows

Cefepime
(5µg) Resistance/Sensitivity Resistance/Sensitivity
No. of (30µg)
Zone of Intermediate Intermediate
Clinical SOURCES Resistant Sensitive Zone of Resistant Sensitive
inhibition Resistant Resistant
isolates (R)* (S)*** inhibition (R)* (S)***
(mm) (IR)** (IR)**
≤14mm ≥18mm (mm) ≤16mm ≥20m
15-17 mm 17-19mm
85 URINE 22 S 22 S
86 URINE 28 S 21 S
87 URINE 13 R 23 S
88 URINE 20 S 21 S
89 URINE 22 S 22 S
90 URINE NILL R 25 S
91 URINE 19 S 22 S
92 URINE 21 S 25 S
93 URINE 22 S 21 S
94 URINE 19 S 22 S
95 URINE 19 S 20 S
96 URINE 20 S 24.5 S
97 URINE 8 R 22.8 S
98 URINE 19 S 22.5 S
99 URINE 20 S 25 S
100 URINE 21 S 22 S
Pseudomonas aeruginosa
101 EAR PUS 31 S 23 S
102 EAR PUS NIL R 13 R
103 EAR PUS 14 R 22 S
104 EAR PUS NIL R 11 R
105 EAR PUS NIL R 27 S
106 EAR PUS NIL R 23 S
107 EAR PUS 27 S 32 S
108 EAR PUS NIL R 21 S
109 EAR PUS NIL R 22 S
110 EAR PUS NIL R 26 S
111 EAR PUS NIL R 24 S
112 EAR PUS NIL R 33 S
113 EAR PUS 15 IR NIL R
114 EAR PUS NIL R 21 S
115 SKIN PUS NIL R 20 S
116 SKIN PUS NIL R 21 S
117 SKIN PUS NIL R NIL R

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CEFIXME Pathogen Shows Pathogen Shows

Cefepime
(5µg) Resistance/Sensitivity Resistance/Sensitivity
No. of (30µg)
Zone of Intermediate Intermediate
Clinical SOURCES Resistant Sensitive Zone of Resistant Sensitive
inhibition Resistant Resistant
isolates (R)* (S)*** inhibition (R)* (S)***
(mm) (IR)** (IR)**
≤14mm ≥18mm (mm) ≤16mm ≥20m
15-17 mm 17-19mm
118 SKIN PUS 24 S 20 S
Salmonella typhi
119 BLOOD 23 S 34 S
120 BLOOD 19 S NIL R
121 BLOOD 21 S 29 S
122 BLOOD 16 IR 16 R
123 BLOOD 21 S 10 R
124 BLOOD 21 S 23 S
125 BLOOD 23 S 17 R
126 BLOOD 15 IR 19 IS
127 BLOOD 30 S 22 S
128 BLOOD 19 S 14 R
129 BLOOD 26 S 11 R
130 BLOOD 19 S 24 S
131 BLOOD 21 S 14 R
132 BLOOD 24 S 21 S
133 BLOOD 23 S 22 S
134 STOOL 23 S 23 S
135 STOOL 22.5 S 22 S
136 STOOL 24 S 21 S
137 STOOL 25 S 24 S
138 STOOL 18 S 23 S
*Resistant (R) means pathogens are not responsive to tested antibiotics.
**Intermediate Resistance (IR) is an indication of non useful therapeutic options similar to the resistant category.
***Susceptible (S) means organisms are responsive to tested antibiotics.

In this investigation there is a variation in the zones of countries like Pakistan, antibiotics are sold as over the
inhibition among the same species of pathogens isolated counter medicines. Self medication is widespread among
from the same source like blood, urine or skin and ear pus the individuals and it is a contributing factor that results
but from different individuals. There are many reasons in emergence of resistance. Poverty is a another driver in
for this variation of zones like one individual has already the developing countries where the use of sub-standard
been treated with the experimental antibiotic many times medicines are frequent and standard drugs are out of the
earlier before the present study, and hence organism may reach of common population, it encourages the self
acquire the resistance as compared to the same pathogen medication, since they are not able to approach the health
isolated from different culture. In many developing care professionals. Low level of literacy results in

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Comparative Study… Ale-Zehra, Baquir Shyum Naqvi, Rabia Bushra and Syeda Qadam Ali

inappropriate doses and incomplete treatment. Some resulting in prolonged illness and greater risk of death.
times individuals had not followed the course regimen Treatment failures also lead to longer periods of
prescribed by the physician; they left the treatment when infectivity.
the symptoms were started to disappear. This incomplete Cefepime might be utilized as a better choice for the
and insufficient exposure of antibiotic to the pathogens infections caused by P.aeruginosa, rather than cefixime
also results in the development of resistance. These are which showed poor susceptibility. Although cefixime had
the few reasons supposed for variation of zones among good activity against P. aeruginosa in the past (33) but its
the same pathogen even isolated from the same sources. irrational use has led to the high resistance now days.
Our study is dealing with the surveillance of anti None of the K. pneumoniae specimen showed nil zones
microbial resistance, future research is strongly by cefepime and only one gave no growth with cefixime.
recommended to evaluate the accurate reasons for the Comparatively higher zones were obtained with cefepime
deviation of zones. Nweneka et al., suggested in his study than cefixime. The in vitro sensitivity test of these
that the dominant factor in the emergence and spread of organisms describes that both antibiotics cefepime and
antibiotic-resistant bacterial pathogens is the intensive cefixime are still effective against different gram positive
use of antibiotic agents; signifying a strong influence of and gram negative pathogens which cause different
behavioral factors in the development of antimicrobial blood, skin, ear, stool and urine infections. They must be
resistance, both from prescribers and patients. Despite prescribed reasonably, keeping in mind that development
that antimicrobial consumption facilitates the of resistance against cefixime and cefepime may pass on
development of antimicrobial resistance; other complex the genes responsible for antibiotic resistance and may
factors need serious considerations (32). The appear after couple of years. A comparative resistance
consequences of resistance are severe. Infections caused pattern of both antibiotics against gram positive and gram
by resistant microbes fail to respond to treatment, negative organisms is shown in figure 1.

Cefixime
90.00
cefepime
80.00
70.00
PERCENTAGE

60.00
50.00
40.00
30.00
20.00
10.00
0.00
E. coli K.pneumoniae S.typhi
CLINICAL ISOLATES

Figure 1: Resistance pattern of Cefixime and Cefepime among different clinical isolates

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Jordan Journal of Pharmaceutical Sciences, Volume 3, No. 2, 2010

development of resistance is an expected consequence of

A difference in susceptibility to antibiotics by irrational use, self-medication and the incomplete course of
microorganisms has become a major factor in drug choice antibiotics attributing towards resistance development. If it is
and success of treatment. Great concerns have been raised going un-controllable, a time will not so far when an
regarding emerging antimicrobial resistance among effective antibiotic would not be able to treat even minor
bacteria that may result in unpredictable antimicrobial infections.
susceptibility and failure of therapy (34, 35). CONCLUSION
Information on resistance is needed at local, national, and Drug resistance is one of the nature’s never ending
international levels to guide decision making and processes leading towards treatment failures. The study
responses. Local information should be used in clinical reveals that the new cefepime, a 4th generation
management and to update treatment guidelines, educate cephalosporin, is a promising antimicrobial agent for
prescribers, and guide infection control policies (36). The various infections caused by Escherichia coli,
study revealed that antibiotic resistance has become a Staphylocoocus aureus , Klebsiella spp., Salmonella typhi
significant problem and will continue as bacteria continue to and Pseudomonas aeruginosa as compared to cefixime, a
grow under the selective pressure of antibiotics. The 3rd generation cephalosporin.

(8) Memon IA, Billoo AG, Memon HI. Cefixime: an oral

REFERENCES option for the treatment of multidrug-resistant enteric
fever in children. South Med J., 1997, 90(12):1204-7.
(1) Smith A. Bacterial resistance to antibiotics. In: Stephen (9) Alfandari S, Bonenfant C, Depretere L, Beaucaire G.
P Denyer, Norman A. Hodges and Sean P (ed) Hugo Use of 27 parenteral antimicrobial agents in north of
and Russell’s Pharmaceutical microbiology. 7th edition. France hospitals. Med Mal Infect., 2007; 37: 103–07.
USA, Blackwell science 2004: 220-222. (10) Mutnick AH, Rhomberg PR, Sader HS, Jones RN.
(2) Tortora GJ, Funke BR, Case C. Microbiology; an Antimicrobial usage and resistance trend relationships
introduction. 9th edition, San Francisco, Pearson from the MYSTIC Programme in North America (1999–
Benjamin Cummings, 2007: 587-603. 2001). J Antimicrob Chemother, 2004; 53: 290–96.
(3) Finch R. Bacterial resistance to antibiotics. In: Stephen (11) Sanders CC. Cefepime: the next generation? Clin Infect
P Denyer, Norman A. Hodges and Sean P (ed) Hugo Dis., 1993;17: 369–79.
and Russell’s Pharmaceutical microbiology. 7th edition. (12) Chapman TM, Perry CM. "Cefepime: a review of its
USA, Blackwell science 2004: 223-225. use in the management of hospitalized patients with
(4) Yahav D, Paul M, Fraser A, Sarid N, and Leibovici L. pneumonia". Am J Respir Med., 2003 2 (1): 75–107.
Efficacy and safety of cefepime: a systematic review (13) Gutierrez K. Pharmacology Review, Newer Antibiotics:
and meta-analysis. Lancet Infect Dis., 2007; 7:338–48. Cefepime. NeoReviews, 2004, 5(9)e 382.
(5) Levinson W. Review of medical microbiology and (14) Sáez-Llorens X, O'Ryan M. Cefepime in the empiric
immunology. New York McGraw Hill, 2004: 72. treatment of meningitis in children. Pediatr Infect Dis.,
(6) Stone JW, Linong G, Andrews JM, Wise, R. Cefixime, J. 2001, 0(3):356-61.
in-vitro activity, pharmacokinetics and tissue penetration. (15) NCCLS. Performance standards for antimicrobial disk
J Antimicrob Chemother., 1989, 23(2):221-8. susceptibility tests; Approved standard, 2000, 7th ed.,
(7) Santillán RM., García1 GR, Benavente IH., García EM. vol 17 (1).
Efficacy of Cefixime in the Therapy of Typhoid Fever. (16) Schwalbe, R, Steele-Moore L, Goodwin.AC.
Proc. West. Pharmacol. Soc., 2000, 43:65-66. Antimicrobial susceptibility testing protocols, 2007;

- 154 - © 2010 DAR Publishers/University of Jordan. All Rights Reserved.

Comparative Study… Ale-Zehra, Baquir Shyum Naqvi, Rabia Bushra and Syeda Qadam Ali

Taylor and Francis Group: 62. (26) Niebla A, González I, Vallín C. Antimicrobial activity
(17) McNulty C , Helicobacte PHLS, Owen R, Tompkins D, of beta-lactams against multiresistant micro-organisms
Hawtin P, McColl K, Price A, Smith G and Teare L. from the family Enterobacteriaceae, and genus
Helicobacter pylori susceptibility testing by disc Pseudomonas. Microbios., 1994;80(325):245-50
diffusion. Journal of Antimicrobial Chemotherapy, (27) Edlund C, Nord CE. Effect on the human normal
2002 49, 601-609. microflora of oral antibiotics for treatment of urinary
(18) Bhat KG, Tripathy A, Rajagopal R, Ramachandran S. A tract infections. J Antimicrob Chemother., 2000; 46
simple broth-disk method to determine the minimum Suppl 1:41-8; discussion 63-5.
inhibitory concentration of ceftriaxone on Salmonella (28) Janknegt R, van der Meer JW. Sequential therapy with
enterica serovar typhi and paratyphi. Indian J Pathol intravenous and oral cephalosporins. J Antimicrob
Microbiol. 2009; 52(2):189-90. Chemother., 1994; 33(1):169-77.
(19) Kulah C, Aktas E, Comert F, Ozlu N, Akyar I, Ankarali (29) Matsumoto Y, Ikemoto A, Tawara S. Antibacterial
H. Detecting imipenem resistance in Acinetobacter activity of cefixime against Salmonella typhi and
baumannii by automated systems (BD Phoenix, applicability of Etest. J Infect Chemother., 1999;
Microscan WalkAway, Vitek 2); high error rates with 5(3):176-179.
Microscan WalkAway. BMC Infect Dis., 2009, 16; 9:30. (30) Girgis NI, Tribble DR, Sultan Y, Farid Z. Short course
(20) Punpanich W, Tantichattanon W, Wongwatcharapaiboon chemotherapy with cefixime in children with multi
S, Treeratweeraphong V. In vitro susceptibility pattern of drug-resistant Salmonella typhi Septicaemia. Pediatr
cephalosporin-resistant Gram-negative bacteria. J Med Infect Dis J., 1995; 14(7):603-5.
Assoc Thai., 2008; 91 Suppl 3:S21-7. (31) Impacts of antibiotic-resistant bacteria, OTA -H-629.
(21) Harada K, Asai T, Ozawa M, Kojima A, Takahashi T. 1995. U.S. Congress, Office of technology assessment.
Farm-level impact of therapeutic antimicrobial use on Washington DC.,pp:05.
antimicrobial-resistant populations of Escherichia coli (32) Nweneka CV, Tapha-Sosseh N, Sosa A. Curbing the
isolates from pigs. Microb Drug Resist., 2008; menace of antimicrobial resistance in developing
14(3):239-44. countries. Harm Reduction Journal, 2009, 6:31.
(22) Speciale A, Musumeci R, Blandino G, Milazzo I, (33) Kumamoto Y, Hirose T, Tanaka N, Hikichi Y, Shigeta
Caccamo F, Nicoletti G. Minimal inhibitory S, Shiraiwa Y, Kameoka H, Yoshida H, Ogata M,
concentrations and time-kill determination of Tazaki H, et al. Comparative studies on activities of
moxifloxacin against aerobic and anaerobic isolates. Int antimicrobial agents against causative organisms
J Antimicrob Agents, 2002; 19(2):111-8. isolated from urinary tract infections (1989). III.
(23) Dambrauskiene A, Adukauskiene D, Jeroch J, Secular changes in susceptibility. Jpn J Antibiot., 1995;
Vitkauskiene A. Pseudomonas aeruginosa bacteremia: 48(9):1174-263.
associations with a source of infection and antibiotic (34) Huang TM, Lin TL, Wu CC. Antimicrobial
resistance. Medicina (Kaunas), 2009; 45(1):1-7. susceptibility and resistance of chicken Escherichia
(24) Bettin A, Suárez P, Bedoya A, Reyes N. coli, Salmonella spp., and Pasteurella multocida
Staphylococcus aureus in residents from a nursing- isolates. Avian Dis., 2009. 53(1):89-93.
home in Cartagena. Rev Salud Publica (Bogota), 2008; (35) Khameneh ZR, Afshar AT. Antimicrobial susceptibility
10(4):650-7. pattern of urinary tract pathogens. Saudi J Kidney Dis
(25) Kum C, Kirkan S, Sekkin S, Akar F, Boyacioglu M. Transpl., 2009; 20(2):251-3.
Comparison of in vitro antimicrobial susceptibility in (36) Williams RJ, Ryan MJ, Surveillance of antimicrobial
Flavobacterium psychrophilum isolated from rainbow resistance an international perspective. BMJ 1998;
trout fry. J Aquat Anim Health, 2008; 20(4):245-51. 317:651-660.

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‫…‪Comparative Study‬‬ ‫‪Ale-Zehra, Baquir Shyum Naqvi, Rabia Bushra and Syeda Qadam Ali‬‬

‫ﺩﺭﺍﺴﺔ ﻤﻘﺎﺭﻨﺔ ﻷﻨﻤﺎﻁ ﻤﻘﺎﻭﻤﺔ ﻤﺴﺒﺒﺎﺕ ﺍﻷﻤﺭﺍﺽ ﻀﺩ ‪ Cefepime‬ﻭ ‪Cefixime‬‬

‫‪3‬‬
‫ﺁﻟﻲ ﺯﻫﻴﺭﺍ‪ ،1‬ﺒﺎﻜﻭﻴﺭ ﻨﺎﻗﻔﻲ‪ ،2‬ﺭﺍﺒﻴﺎ ﺒﺸﺭ‪ ،*2‬ﻭﺴﻴﺩﺍ ﻗﺩﻡ ﻋﻠﻲ‬

‫‪ 1‬ﻤﺴﺘﺸﻔﻰ ﺁﻏﺎ ﺨﺎﻥ ﺍﻟﺠﺎﻤﻌﻲ‪ ،‬ﻜﺭﺍﺘﺸﻲ‪ ،‬ﺒﺎﻜﺴﺘﺎﻥ‪.‬‬

‫‪ 2‬ﻗﺴﻡ ﺍﻟﺼﻴﺩﻻﻨﻴﺎﺕ‪ ،‬ﻜﻠﻴﺔ ﺍﻟﺼﻴﺩﻟﺔ‪ ،‬ﺠﺎﻤﻌﺔ ﻜﺭﺍﺘﺸﻲ‪.‬‬
‫‪ 3‬ﻜﻠﻴﺔ ﻀﻴﺎﺀ ﺍﻟﺩﻴﻥ ﻟﻠﺼﻴﺩﻟﺔ‪ ،‬ﺠﺎﻤﻌﺔ ﻀﻴﺎﺀ ﺍﻟﺩﻴﻥ‪.‬‬

‫ﻤﻠﺨـﺹ‬

‫ﺃﺩﻯ ﺍﻹﺴﺘﺨﺩﺍﻡ ﺍﻟﺨﺎﻁﺊ ﻟﻠﻤﻀﺎﺩﺍﺕ ﺍﻟﺤﻴﻭﻴﺔ ﺇﻟﻰ ﺯﻴﺎﺩﺓ ﻤﻘﺎﻭﻤﺔ ﺍﻟﺠﺭﺍﺜﻴﻡ ﻟﻸﺩﻭﻴﺔ ﻤﻤﺎ ﺃﺩﻯ ﺇﻟﻰ ﺍﻻﻋﺘﻘﺎﺩ ﺒﺄﻥ ﻋﺼﺭ ﺍﻟﻤﻀﺎﺩﺍﺕ‬
‫ﺍﻟﺤﻴﻭﻴﺔ ﻗﺎﺭﺏ ﻋﻠﻰ ﺍﻹﻨﺘﻬﺎﺀ‪.‬ﺇﻥ ﺘﻘﻴﻴﻡ ﻓﻌﺎﻟﻴﺔ ﺍﻟﻤﻀﺎﺩﺍﺕ ﺍﻟﺤﻴﻭﻴﺔ ﺃﻤﺭ ﻫﺎﻡ ﻟﻀﻤﺎﻥ ﺍﻟﺤﺼﻭل ﻋﻠﻰ ﻨﺘﺎﺌﺞ ﺠﻴﺩﺓ ﻟﻠﻌﻼﺝ‪.‬‬
‫ﻭﺍﻟﻐﺭﺽ ﻤﻥ ﻫﺫﻩ ﺍﻟﺩﺭﺍﺴﺔ ﺘﻘﻴﻴﻡ ﻤﻘﺎﻭﻤﺔ ﻏﺯﻻﺕ ﻀﺩ ‪) cefixime‬ﻤﻥ ﺍﻟﺠﻴل ﺍﻟﺜﺎﻟﺙ ﻟﻠﺴﻴﻔﺎﻟﻭﺭﺴﺒﻭﺭﻴﻥ( ﻭ ‪) Cefepime‬ﻤﻥ‬
‫ﺍﻟﺠﻴل ﺍﻟﺭﺍﺒﻊ ﻟﻠﺴﻴﻔﺎﻟﻭﺴﺒﻭﺭﻴﻥ (‪ .‬ﻭﺘﺴﺠل ﺍﻟﺩﺭﺍﺴﺔ ‪ 138‬ﻋﺯﻟﺔ ﺴﺭﻴﺭﻴﺔ ﻤﻨﻬﺎ )‪ Escherichia coli (%30‬ﻭ) ‪(%30‬‬
‫‪ Staphlococcus aureus‬ﻭ )‪ Salmonella typhi (%14‬ﻭ )‪ Klebsiella pneumoniae (%13‬ﻭ )‪(%13‬‬
‫‪ Pseudomonas aeruginosa‬ﻭﻗﺩ ﺘﻡ ﺘﺠﻤﻴﻊ ﺍﻟﻌﺯﻻﺕ ﺨﻼل ﺴﻨﺔ )ﻤﻥ ﻜﺎﻨﻭﻥ ﺍﻟﺜﺎﻨﻲ ‪ – 2008‬ﻜﺎﻨﻭﻥ ﺍﻟﺜﺎﻨﻲ ‪( 2009‬‬
‫ﻤﻥ ﻤﺨﺘﺒﺭﺍﺕ ﻋﻠﻡ ﺍﻷﻤﺭﺍﺽ ﻤﻥ ﻤﺴﺘﺸﻔﻴﺎﺕ ﻤﺨﺘﻠﻔﺔ ﻓﻲ ﻜﺭﺍﺘﺸﻲ‪ /‬ﺒﺎﻜﺴﺘﺎﻥ ﻭﺘﺴﺠﻴل ‪ 59‬ﻋﻴﻨﺔ ﺒﻭل ‪30 ،‬ﻋﻴﻨﺔ ﻗﻴﺢ ﺠﻠﺩﻱ‬
‫‪ 29 ،‬ﻋﻴﻨﺔ ﻗﻴﺢ ﺃﺫﻨﻲ ‪15 ،‬ﻋﻴﻨﺔ ﺩﻡ ‪ ،‬ﻭ ‪5‬ﻋﻴﻨﺎﺕ ﺒﺭﺍﺯ‪ ،‬ﺘﺤﺕ ﺩﺭﺍﺴﺔ ﺍﻟﺤﺴﺎﺴﻴﺔ ﻟﻠﻤﻀﺎﺩﺍﺕ ﺍﻟﺤﻴﻭﻴﺔ ﺨﺎﺭﺝ ﺍﻟﺠﺴﻡ‬
‫ﺒﺎﺴﺘﺨﺩﺍﻡ ﺍﻟﻤﻌﻴﺎﺭ ‪. 0.5 McFarland‬‬
‫ﺃﻅﻬﺭﺕ ﺍﻟﻨﺘﺎﺌﺞ ﺃﻥ ‪ Cefepime‬ﻜﺎﻥ ﻟﻪ ﺘﺄﺜﻴﺭ ﻋﻠﻰ ‪Staphlococcus aureus%85 ، Escherichia coli %92.6‬‬
‫‪ Pseudomonas aeruginosa %77.77 ، Klebsiella pneumoniae %94،‬ﻭ ‪.Salmonella typhi %65‬‬
‫‪ Cefexime‬ﻜﺎﻥ ﺃﻗل ﻓﻌﺎﻟﻴﺔ ﻀﺩ ‪ (%16.66) Pseudomonas aeruginosa‬ﺒﻴﻨﻤﺎ ﻅﻬﺭﺕ ﺍﻟﻔﻌﺎﻟﻴﺔ ﺍﻷﻓﻀل ﺘﺠﺎﻩ‬
‫‪ .(%90) Salmonella typhi‬ﻴﺨﻠﺹ ﺍﻟﺒﺤﺙ ﺇﻟﻰ ﻀﺭﻭﺭﺓ ﺍﻟﺴﻌﻲ ﻟﺘﻌﺯﻴﺯ ﺍﻟﺠﻬﻭﺩ ﺍﻟﻤﺭﺍﻓﻘﺔ ﻟﻠﻤﺤﺎﻓﻅﺔ ﻋﻠﻰ ﻓﻌﺎﻟﻴﺔ ﻫﺫﻩ‬
‫ﺍﻟﻤﺠﻤﻭﻋﺎﺕ ﺍﻟﺩﻭﺍﺌﻴﺔ ﻀﺩ ﺍﺴﺘﻤﺭﺍﺭﻴﺔ ﺘﻜﻭﻴﻥ ﺴﻼﻻﺕ ﻤﻘﺎﻭﻤﺔ ﻟﻬﺎ‪.‬‬

‫ﺍﻟﻜﻠﻤﺎﺕ ﺍﻟﺩﺍﻟﺔ‪ :‬ﺴﻴﻔﻴﻜﺴﻴﻡ‪ ،‬ﺴﻴﻔﻴﺒﻴﻡ‪ ،‬ﻁﺭﻴﻘﺔ ﺍﻨﺘﺸﺎﺭ ﺍﻟﻘﺭﺹ‪ ،‬ﻤﻘﺎﻭﻤﺔ ﺍﻟﺠﺭﺍﺜﻴﻡ‪ ،‬ﻤﻤﺭﺽ‪ ،‬ﻜﺭﺍﺘﺸﻲ‪ ،‬ﺒﺎﻜﺴﺘﺎﻥ‪.‬‬

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‫ﺘﺎﺭﻴﺦ ﺍﺴﺘﻼﻡ ﺍﻟﺒﺤﺙ ‪ 2009/10/14‬ﻭﺘﺎﺭﻴﺦ ﻗﺒﻭﻟﻪ ﻟﻠﻨﺸﺭ ‪.2010/3/30‬‬

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