I P S F E D U C A T I O N A L S U P P L E M E N T

ISSUE NO. 15 JULY 2008

2 International Pharmaceutical Students’ Federation

Message From IPSF

Dear Readers,

It is the pleasure of International Pharmaceutical

Students' Federation (IPSF) to present you this

issue of Phuture under the theme “Antibiotic

resistance”. Through this issue, IPSF wants to

spread some information of antibiotic resistance

and discuss the ways to prevent and alleviate this

problem.

Over the past decade, the dramatic upsurge in the

spread of drug-resistant microbes throughout the

globe has occurred. Many infectious diseases are

becoming complex and difficult to treat and the

treatment is becoming expensive.

Antibiotic resistance is a major problem of present

therapy. Antibiotic resistance is a major global

problem worldwide especially in the developing

countries. Increasing use of antimicrobials in

humans, animals, and agriculture has resulted in

many microbes developing resistance to these

drugs. Many infectious diseases are increasingly

difficult to treat because of antimicrobial-resistant

organisms. The irrational prescribing, poly-

pharmacy, self medication and lack of legislative

framework for antibiotic prescription are the key

factors for the development of antibiotic

resistance. It is time that we take action. Many

things can be done from the position where you

are: whether you are a policy-maker, health care

professional, health advocate or member of the

public, can do to help tackle the problem. In this

context, IPSF has published this scientific

supplement on the theme antibiotic resistance.

This issue contains articles by expertise in the field

of microbiology, antibiotics research and students.

We are very grateful to all the authors for their kind

contributions. Though antibiotic resistance is a

broad term to embrace in this supplement, we

have tried to show a glance on this growing global

problem. We expect that the information and

thoughts presented here will be useful and be able

to stimulate and encourage readers to contribute

in prevention and control for this growing problem

to some extent.

Enjoy reading!

Suresh PantheeIPSF Chairperson of Education 2007-08

Table of Contents

Antibiotic Use and Emerging Bacterial Resistance

ESBL producing bacteria: Growing problem for

antibiotic resistance

Emergence and spread of antibiotic resistance in

bacterial pathogens with special emphasis on

nosocomial infections

National Antibiotic Policy in the context of India

Preventing Antimicrobial Resistance: Role of

pharmacy student

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Dr. Robert E. Siegel

Dr. Malay Ranjan Sen and Amitabha Bhattacharjee

Prof. Dr. Wolfgang Witte

Arati Sharma

Atmika Paudel and Binaya Sapkota

Cover design by Tendy Rusdiana

3Phuture - Antibiotic Resistetance2008

Antibiotic Use and Emerging Bacterial Resistance

World-wide bacterial resistance rates continue to increase and Target alteration, as seen with altered penicillin binding proteins

national resistance rates reflect overall antibiotic use in each (PBP) 2. Chemical warfare, as seen with beta-lactamase

country. Over 60% of all antibiotics consumed in the US are production and 3. Decreased antibiotic concentration in bacteria,

used in the animal industry both as anabolic agents to increase either by porin protein changes reducing antibiotic entry or up

animal growth and to prevent the spread of infections, as regulation of efflux pump activity, extruding more antibiotic from

animals are crowded into confined living spaces. The farming of the bacteria.

fish and seafood has also led to the increased use of antibiotics, Higher resistance rates are being reported in community since a dense population facilitates the spread of infectious organisms, such as MDR Streptococcus pneumoniae and MRSA, agents. A recent study of fish and shrimp in Canada showed as well as Gram negative pathogens such as E. coli and that many contain veterinary drug residues, including Enterobacter cloacae. In the critical care setting, rising rates of antibiotics. Bacterial resistance is increasingly seen as a public Pseudomonas aeruginosa and Acinetobacter baumannii are health threat since few new antibiotics options are being additional problems, with highly resistant pathogens leaving introduced. The Infectious Diseases Society of America (IDSA) clinicians few treatment alternatives. The rigid division between education campaign of “Bad Bugs, No Drugs” was begun to raise community-acquired organisms and hospital-acquired public awareness of this problem. organisms has been blurred since so many patients visit the

Doctors frequently prescribe antibiotics for upper respiratory hospital for therapy or reside in nursing homes.

tract infections (URI) even though most of are viral in origin.

Patient expectations to assure they can return to work or school

places caregivers in an uncomfortable position, in which they Rising rates of PRSP and multi-drug resistance S. pneumonia

cannot withhold antibiotics. A study of primary care practice (MDRSP) are changing the way pulmonary infections are treated.

shows that there are approximately 25 million visits to Resistance to β-lactam antibiotics is due to expression of a low

physicians for URI symptoms, and that although less than 1% affinity PBPs. Macrolide resistance is due to one of two

are estimated to be due to bacteria, approximately one third of mechanisms: up regulation of the efflux pump Mef(A), leading to

patients are prescribed an antibiotic. Acute bronchitis, in low-level resistance which may be overcome by high antibiotic

otherwise healthy nonsmokers, is usually a viral illness and a concentration, or a ribosomal target change Erm(B), which can

meta-analysis of 8 placebo controlled trials showed that cause very high MICs and lead to clinical failure. These

antibiotic reduced the duration of patient symptoms by less than resistance rates are being driven by overuse of antibiotics for

a day. The presence of purulent sputum does not indicate a upper RTIs. Pneumococcal macrolide resistance rates over 30%

bacterial etiology and symptoms of cough and sputum are reported in many parts of the US, driving increased use of

production commonly last 1-2 weeks. Many patients complain respiratory fluoroquinolones for patients who have community-

that without antibiotics infection spreads into their chest, but acquired pneumonia (CAP) with risk factors for resistance. Risk

they may actually be suffering virally induced bronchospasm, factors include recent antibiotic therapy, previous stay in a risk

which may respond to inhaled bronchodilators. The area (day care, prison, homeless shelter, or nursing home),

recommended approach for acute bronchitis, consists of alcoholism and previous RTI. If an isolate is penicillin resistant,

medications to treat symptoms, including cough suppression, only 20% of the isolates will be macrolide susceptible.

and reassurance that antibiotic will be prescribed if the condition Susceptibility rates of S. pneumoniae to the respiratory

deteriorates. When antibiotics are necessary, a macrolide or fluoroquinolones, levofloxacin, gemifloxacin and moxifloxacin

doxycycline to cover atypical pathogens and Streptococcus have been stable at about 99%, but rates for ciprofloxacin are

pneumoniae is usually adequate.much lower reported at 82%. In the US, ciprofloxacin has

Prolonged, more traditional courses of antibiotics are now recently become a generic product, raising concern, since discouraged. The CDC recommends implementing policies to therapeutic substitution for the respiratory FQs may drive limit antibiotic overuse, and the World Health Organization overuse of ciprofloxacin, increasing S. pneumoniae FQ resistance suggests the use of the most potent antibiotic for the shortest rates, and risking the utility of this important class of antibiotics.duration. In a study of children ages 6 mos-5 years with URI

Hemophilus influenzae resistance is due to the production of a β-symptoms, conducted in the Dominican Republic, patients were

lactamases, which destroy penicillin derivatives and first-randomized to amoxicillin with standard dosing of 40 mg/kg/day

generation cephalosporins. Rates of resistance from sinus for 10 days or high-dose, short course (HDSC) therapy of 90

isolates are about 30% for penicillin and 40% for macrolides in mg/kg/day for 5 days. At the end of a month, the pharynx was

the US and β-lactamase production was almost 50% in a study in swabbed to detect penicillin-resistant S. pneumoniae (PRSP).

Bangkok, Thailand. Sinus infections are similar to an abscess Resistance rates were 24% for HDSC, 32% for standard dose

or an undrained collection with poor perfusion into the infected p=.03, and there was less TMP/SMZ resistance in the HDSC

area. Resistance may have more significance in sinusitis than in group as well. The 2005 ATS/IDSA Guidelines for the treatment

lung infections, where high concentrations of antibiotics can of HAP, VAP and Healthcare-acquired pneumonia (HCAP)

typically be achieved due to high blood flow.recommends that VAP be treated for 7-8 days of antimicrobial

S. aureus resistance has long been a hospital problem and 70% therapy if the patient is started on the appropriate antibiotic of all hospital isolates are MRSA. Recently, community-acquired from the beginning and responds to therapy. Longer treatment MRSA is also becoming common, and may produce the toxin duration simply lead to colonization with resistant bacteria, Panton-Valentine leukocidin (PVL). These strains are typically since sensitive bacteria are killed, and resistant mutants survive resistant to oxacillin, macrolides and fluoroquinolones, but to become the dominant pathogen. sensitive to doxycyline and TMP/SMZ, in addition to the drugs

that treat health care strains: vancomycin, linezolid and

daptomycin. Originally seen in athletes, infants, IV drug users There are three main mechanisms of antibiotic resistance: 1.

Community Organisms:

Resistance:

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Dr. Robert E. Siegel, Director, Pulmonary and Critical Care Medicine, James J. Peters Veterans Affairs Medical Center, 130 W. Kingsbridge Road, Bronx NY, 10468, Associate Professor of Medicine, Mount Sinai School of Medicine, New York, NY E-mail:

robert.siegel@va.gov, Telephone: 917-842-6975, Fax: 718-741-4623

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and prisoners, the community strain is now reported in patients administering vaccines and adhering to hand washing along with

without identifiable risk factors. It most commonly causes skin other infection control practices. In the ICU, simple techniques,

infections such as furunculosis, but may also produce more such as elevating the head of the bed, daily sedation vacation to

serious infections including necrotizing pneumonia. Treatment accelerate extubation of mechanically ventilated patients and

of skin infections frequently includes surgical drainage and oral identification and isolation of patients infected with resistant

antibiotics and washing linens and towels in the in hot water to pathogens are important. In this way, we hope to maintain our

prevent re-infection. antibiotic susceptibilities, as best we can, until new antibiotic

classes are developed which can add to our armamentarium

against the ever evolving pathogens we confront on a daily basis.

Finally, gram negative resistance remains an increasingly

serious problem, and the most common mechanism is β-

lactamase production, with over 700 β-lactamases having 1. Granizo JJ, Aguilar L, Casal J, Garcia-Rey C, Dal-Re R, Baquero been described.13 Resistance in community acquired F. Streptococcus pneumoniae resistance to erythromycin and enterobacteraciae is being reported with E. coli and Klebsiella penicillin in relation to macrolide and beta-lactam pneumoniae due to extended-spectrum β-lactamase (ESBL) consumption in Spain (1979-1997). J Antimicrob Chemother. production of the CTX-M type and these isolates may be MDR 2000;46(5):767-73.with FQ, aminoglycoside and sulfonamide resistance. E. coli

2. Tittlemier SA, Van de Riet J, Burns G, Potter R, Murphy C, resistance to levofloxacin and ciprofloxacin is now reported to

Rourke W, et al. Analysis of veterinary drug residues in fish be about 10% of isolates in the US, and being driven by

and shrimp composites collected during the Canadian Total widespread use of FQs for various infections including URIs and

Dieg Study, 1993-2004. Food Addit Contam. 2007;24(1):14-UTIs. Enterobacter cloacae hyper-production of Amp C β-

20.lactamase causing third generation cephalosporin resistance is

3. Infectious Diseases Society of America. Bad bugs, no drugs. also being reported among hospitalized patients. ESBL As antibiotic discovery stagnates…a public health crisis brews. production may be missed unless specific tests are performed Alexandria, VA: Infectious Diseases Society of America; 2004.by the microbiology lab to detect it and bacteria may test

susceptible to cephalosporins by conventional breakpoints, 4. Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive

although clinical failure is possible if they are ESBL producers. antibiotic use for acute respiratory infections in the United

States. Clin Infect Dis. 2001:33(6):757-62.Pseudomonas aeruginosa and Acinetobacter baumannii are

two ICU pathogens associated with higher mortality in HAP. P. 5. Bent S, Saint S, Vittinghoff E, Grady D. Antibiotics in acute

aeruginosa is the most common causative ICU pathogen for bronchitis: a meta-analysis. Am J Med.1999;107:62-7.

HAP and UTI. Resistance is due to multiple mechanisms 6. Schrag SJ, Peña C, Fernández J, Sánchez J, Gómez V, Pérez E, including ESBL production targeting cephalosporins, and both Feris JM, Besser RE. Effect of short-course, high-dose an Opr-D porin protein change and up regulation of efflux amoxicillin therapy on resistant pneumococcal carriage: a pumps to cause carbapenem resistance. A. baumannii causes randomized trial. JAMA. 2001;286(1):49-56. sporadic outbreaks and although not a highly pathogenic

7. American Thoracic Society/Infectious Diseases Society of organism, it is persistent on environmental surfaces and

America. Guidelines for the treatment of adults with hospital-causes HAP or other hospital acquired infections. It is being

acquired, ventilator-associated, and healthcare-associated reported in returning US soldiers from the Middle East due to

pneumonia. Am J Respir Crit Care Med 2005;171(4):388-the presence of this soil organism in wounds and hospitals.

416.Frequently it is only sensitive to polymyxin and tigecycline, and

8. Ruhe JJ, Myers L, Mushatt D, Hasbun R. High-level penicillin-colistin is being nebulized for pulmonary infections to limit nonsusceptible Streptococcus pneumoniae bacteremia: renal and CNS toxicity. Infection control practices are crucial to identification of a low-risk subgroup. Clin Infect Dis. prevent spread of this organism and local outbreaks.2004;38(4):508-14.

9. TRUST study (Tracking Resistance in the US Today),

Postgraduate Med (Suppl), In Press.The major hope to limit bacterial resistance rates is to promote

10. Critchley IA, Brown SD, Traczewski MM, Tillotson GS, Janjic N. the appropriate use antibiotics. First, they should be used in

National and redional assessment of antimicrobial resistance cases of suspected bacterial infection only. Newer methods of

among communigy-acquired respiratory tract pathogens achieving microbiologic eradication and clinical cure should be

identified in a 2005-2006 U.S. Faropenem surveillance study. employed: use of prolonged infusions of β-lactam antibiotics to

Antimicrob Aents Chemother. 2007;51(12):4382-9.take advantage of time dependent killing pharmacodynamics

(PD), and the FQs as HDSC regimes to take advantage of 11. Srifuengfung S, Chayakulkeeree M, Chokephaibulkit K, concentration-dependent killing PD. Also, use of the most Tribuddharat C. Five-year study of antimicrobial susceptibility potent antibiotic for the shortest duration should be employed, and beta-lactamase production in Haemophilus infuenzae. instead of long courses which promote permissive growth of Southeast Asian J Trop Med Public Health. 2007;38(4):732-6.resistant bacteria. De-escalation of antibiotics in the ICU is

12. Siegel RE. The significance of serum versus tissue level of recommended by the ATS/IDSA guidelines for the treatment of

antibiotics in the treatment of penicillin-resistant HAP/VAP and HCAP and should be extended to all ICU

Streptococcus pneumonia and community-acquired infections.7 This includes stopping antibiotics if infection is not

pneumonia. Are we looking in the wrong place? Chest apparent after antibiotics are initiated, and changing to

1999;116(2):535-538.narrow-spectrum agents if resistant pathogens are not isolated

13. Perez F, Endimiani A, Hujer KM, Bonomo RA. The continuing or if a susceptible pathogen is identified. All antibiotic classes challenge of ESBLS. Curr Opin Pharmacol. 2007;7(5):459-should continue to be prescribed, so that resistance pressure 469. for any one antibiotic class is limited. Finally, we should

continue infection preventive measures, including

Gram-negative bacteria resistance

References:

Practices to help maintain susceptibilities:

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5Phuture - Antibiotic Resistetance2008

ESBL producing bacteria: Growing problem for antibiotic resistance

Introduction

Spectrum of ESBL producing organism:

Genetic environment of ESBL gene

Epidemiology

What are ESBLs?

More than 150 different natural ESBL variants are known at

present, and the list seems to be far from complete The evolution of bacteria through time has permitted the (http://www.lahey.org/studies/webt.htm). They have been elaboration of a range of diverse species. These many species classified in to nine distinct structural/evolutionary families have generated a corresponding diversity of resistance based on comparisons of their deduced amino acid sequences mechanisms that fight naturally occurring antibiotic challenges, e.g. TEM, SHV, CTX M, OXA, PER, VEB, GES, TLA, BES.such as those generated by molds, yeasts and actinomycetes.

As a result, even bacteria that have never been exposed to

commercial antibiotics can nonetheless bear resistance genes to

these drugs. So far ESBL activity is observed only in Gram negative

organisms. They are mainly found in Escherichia coli, Klebsiella In recent years, there has been a growing prevalence of Gram

pneumoniae, Proteus mirabilis, however, also occur in other negative organisms which have almost replaced Staphylococcus

members of Enterobacteriaceae family as well as in non aureus in nosocomial infections. It is also observed that Gram

fermenting Gram negative rods like Pseudomonas and negative bacteria were the most common blood stream

Acinetobacter species. Recently it was also reported in pathogens. Moreover fatalities among patients infected with

Haemophilus influenzae. Gram negative bacilli are higher than those among patients who

have Gram positive cocci as causative agents. The situation

complicates more with the isolation of the organisms that are

resistant to multiple antibiotics especially against beta lactam The increasing pattern of antibiotic resistance of these organisms antibiotics. prompted the genetic environment studies. The gene pool might

The β-lactamases are the major defense of Gram negative already be firmly studied, and besides, the procurement and

bacteria against β-lactam antibiotics. These enzymes contain an expression of new genetic material, even antibiotic resistant

active site consisting of a narrow longitudinal groove, with a genes might be influenced by other factors other than antibiotic

cavity on its floor (the oxyanion pocket), which is loosely challenge. The widespread clinical use of commercial antibiotics

constructed in order to have conformational flexibility in terms has mobilized latent mechanisms to neutralize their impact. This

of substrate binding. Close to this lies the serine residue that process has been further facilitated by the variety of genetic

irreversibly reacts with the carbonyl carbon of the β-lactam ring, elements that can harbor resistance genes, including the

resulting in an open ring (inactive β-lactam) and regenerating bacterial chromosome, transferable plasmid and transposons.

the β-lactamase. β-Lactamases, serine residue at the active The dominance of a single genetic entity or piece (gene or series

site, similar to bacterial penicillin binding proteins, is estimated of genes) appears to be more influenced by its surrounding DNA

from current sequence diversity to have evolved with bacteria than the gene itself, either by facilitating rapid mobilization

over past 2 billion years. Since β-lactam antibiotics came in to and/or encoding other functions. The mobile genetic elements

clinical use, these enzymes coevolved with them. Around 20 like plasmids and transposons reported to contain genetic units

years ago, agents resistant to common β-lactamase enzymes named integrons, contain genes for site specific recombination

were introduced, which include third generation cephalosporins system, capable of capturing and mobilizing genes called gene

and the monobactam. Bacteria responded with a new β cassettes. Although there could be independent existence of both

lactamase called “extended spectrum β-lactamase” (ESBL) with the gene cassette and ESBL gene in a particular organism, ESBL

variable success, can confer resistance to the latest third and genes are also reported to be located on integrons, which

fourth generation cephalosporins and monobactam. Today more facilitate their horizontal transfer to other related as well as

than hundreds of ESBL variants have been described and have unrelated microbes.

been given variety of names on the basis of their substrate

spectrum and functional groups. The selection pressure that

drives ESBL evolution has usually been attributed to the intense Large-scale surveillance studies, such as the SENTRY

use of oxyimino cephalosporins, mainly third generation Antimicrobial Surveillance Program, have been a source of useful

cephalosporins.data regarding the regional prevalence of ESBL-producing

isolates. The estimated prevalence of ESBL-producing strains of

E. coli and K. pneumoniae in the United States was relatively low There is no consensus of the precise definition of ESBLs. A whereas, it was quite high in the Asia-Pacific region and in Latin commonly working definition is that the ESBLs are capable of America. In a survey almost 2800 Klebsiella species isolates conferring bacterial resistance to the penicillins, first, second, recovered from more than 30 US medical centers from 1997 and third generation cephalosporins and aztreonam (but not the through 2000 found that 6-7% were phenotypically ESBL cephamycins or carbapenems) by hydrolysis of these positive. In a survey of 2000 E. coli and K. pneumoniae isolates antibiotics, and which are inhibited by β-lactamase inhibitors, from the Asia-Pacific and South Africa region, a relatively larger such as clavulanic acid, sulbactam and tazobactam. proportion of potential ESBL producers (25% in Klebsiella

pneumoniae and 10% in E. coli) were confirmed. In Latin America ESBLs are usually described as acquired β lactamases that are

and Europe the survey showed 44-46% and 23% of Klebsiella encoded mostly by plasmid located genes. Though, the first

species respectively and 5% of E. coli were positive for ESBL clinical isolates expressing acquired ESBLs were identified in

production. In India prevalence of ESBL producers in Germany, the first nosocomial outbreaks caused by ESBL

Enterobacteriaceae varies grossly from 12.6 to 86.6% among producers started to occur in France in 1985 and then in USA.

different centers.The number of ESBL variants identified has been constantly

growing since 1983, demonstrating a rapid ESBL evolution.

Dr. Malay Ranjan Sen, Professor and Amitabha Bhattacharjee, Senior Research FellowDepartment of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, INDIA email:

mr_senbhu@yahoo.com and ab_0404@rediffmail.com

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Impact on Antimicrobial therapy

Conclusion

References:

ESBL producing isolates are frequently resistant to other kinds

of antimicrobials, aminoglycosides, quinolones and co- The relatively low level of accuracy in testing for ESBLs reported trimoxazole. What is especially frustrating is that genes coding for many clinical laboratories suggests that clinical failures might for ESBLs and, and for example aminoglycoside modifying be occurring at higher rates in the general population than what enzymes (AMEs) often reside within the same conjugative indicated by published clinical studies. In a study of ESBL-plasmids and therefore are transmitted together from one mediated resistance in 220 Klebsiella species isolates recovered strain to another. This means that resistance to two different from 35 intensive care units in Europe, communicating kinds of drugs may be co selected by the use of either one. Bell laboratories incorrectly reported the susceptibilities of a large and Turnidge demonstrated that, in 1998 99 in Western Pacific proportion of isolates. In a study, 28.9% of the ESBL-producing countries and South Africa, the frequency of resistance in ESBL isolates tested were reported to be susceptible to ceftriaxone, and producing Enterobacter cloacae to gentamicin, ciprofloxacin 36.6% were reported to be susceptible to cefotaxime. A and co trimoxazole could reach values of approximately 65%, discrepancy of this kind is quite disturbing, because even low 60% and 20% respectively. levels of in vitro resistance can lead clinical failure. Such an

In recent years, ESBLs have become more prevalent in species occurrence was also reported during a nosocomial outbreak of

characterized by inducible class C cephalosporinases (AmpC), multidrug-resistant K. pneumoniae. The isolates exhibited a

such as Enterobacter spp., Citrobacter freundii and Serratia mode MIC for cefotaxime of 2 mg/L, indicating a low level of

marcenscens, which frequently segregate mutants with high resistance. Although a regimen that included cefotaxime or

level constitutive production of AmpC enzymes.Strains that are ceftriaxone proved to be effective in treating cases of

both ESBL producers and AmpC de repressed mutants have uncomplicated urinary tract infection, these antimicrobials failed

been already identified in studies, despite the masking of the to treat major infections at other sites.

ESBL phenotype by the inhibitor resistance of AmpC-β The complexity of resistance development is still evolving and lactamases. further investigation should be continued regarding their

In vitro, the carbapenems (imipenem and meropenem) and the mechanism of resistance supported by genetic data to design

cephamycins have the most consistent activity against ESBL novel antibiotic classes against these pathogens. Beside these,

producing organisms, given their stability to hydrolysis by continuous surveillance studies should be under taken on region

ESBLs. Indeed, published reports of carbapenems resistance in basis so as to help clinicians, pharmacologists and researchers.

organisms such as K. pneumoniae are exceedingly rare. The

plasmid harboring genes encoding ESBLs frequently also

contain genes encoding mechanisms of resistance to 1. Bradford, P. A. Extended spectrum β-Lactamases in the 21st aminoglycosides and trimethoprim sulfomethoxazole. There is Century: Characterization, Epidemiology and Detection of this also strong association between quinolone resistance and ESBL important resistance threat. Clin Microbiol Rev 2001; 14: 933 production. 951.

In vitro synergy may be achievable between cefepime and 2. Bhattacharjee, A., Sen, M. R., Prakash, P., Anupurba, S. Role amikacin against ESBL producing organisms but cefepime of ß-lactamase inhibitors in enterobacterial isolates producing should not be used as a therapy against ESBL producing extended-spectrum b-lactamases. Journal of Antimicrobial organisms. Based on in vitro studies, the cephamycins appear Chemotherapy 2008; 61: 309 314.an attractive option for use against ESBL producers. However,

3. Trevino, S., Mahon, C. R., Bacteremia (2000). In Mahon C R., published clinical experience with these drugs is almost lacking.

Manuselis, J. Text book of Diagnostic Microbiology, 2nd The only reports describe in vivo selection of porin deficient

edition. Philadelphia: W B Saunders company 998 1008.mutants during therapy. In general cefotetan has lower MICs

4. Bush, K., Jacoby, G A., Medeiros A A. A functional classification than cefoxitin, and should be preferentially used. However, scheme for β-lactamases and its correlation with molecular cephamycin therapy leads to emergence of plasmid mediated structure. Antimicrob Agents Chemother 1995; 39: 1211 33.AmpC resistance.

5. Palucha, A., Mikiewicz, B. et al. Concurrent outbreaks of As per with the cephalosporins, combinations of β-lactam with extended spectrum β-lactamase producing organisms of the β-lactamase inhibitor are also subject to rising MICs as family Enterobacteriaceae in a Warsaw hospital. J Antimicrob inoculum rises. Treatment with β-lactam/β-lactamase inhibitor Chemother 1999; 44: 489 99.combination was shown to be inferior to the treatment with

imipenem or piperacillin/tazobactam plus aminoglycoside 6. Paterson, D. L. Recommendation for treatment of severe

combination in an animal model. Piperacillin/tazobactam was infections caused by Enterobacteriaceae producing extended

found to be an attractive option with high susceptibility and was spectrum β-lactamases (ESBLs). Clin Microbiol Infect 2000;

also recommended for treatment to control ESBL producing 6: 460 463.

Enterobacteriaceae.

Carbapenems should be regarded as the drugs of choice for

serious infections with ESBL producing organisms. The basis for

this statement is not just the almost uniform in vitro

susceptibility but also increasingly extensive clinical

experience. The choice between imipenem and meropenem is

difficult. Published experience is greatest with imipenem, but

MICs for meropenem is slightly lower than for imipenem. In

vitro studies with a new carbapenem (L 749, 345) capable of

once daily administration showed that it shared the excellent

activity against ESBL producing organism than imipenem and

meropenem.

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7Phuture - Antibiotic Resistetance2008

Emergence And Spread Of Antibiotic Resistance In Bacterial Pathogens With Special Emphasis On Nosocomial Infections

Understanding of emergence of antibiotic resistance needs to resistance genes are integrated into conjugative plasmids and

know about the molecular mechanisms by which bacteria this con reach a wide dissemination.

counteract their mode(s) of action. Genetic events rendering bacteria antibiotic resistant always

In the following prominent examples for different resistance take place at more or less low frequencies. Whether this results in

mechanisms are described. emergence and spread of a resistant bacterial colonizer or

pathogen is largely dependent upon antibiotic selective pressure Mykobacteria: resistance in natural habitates as well as in the microflora of humans and to rifampicin due to amino acid exchanges of the -subunit of RNA other animals treated with antibiotics.polymerase, resistance to streptomycin due to amino acid

exchanges in the smal l unit of the r ibosome. Dissemination of resistance takes place in different ways, most

Enterobacter iaceae, staphylococc i , pneumococc i: simply by clonal spread of the bacteria (bacterial strains) which

fluoroquinolones resistance due to amino acid examples in DNA have acquired a resistance gene(s). A second dimension is

gyrase (preferentially gram-negatives) and in topoisomerase IV between different strains of a particular bacterial species,

(preferentially in gram-positives). between different families and even among gram-negative and

gram-positive bacterial (prominent example: tetM mediating macrolide, resistance to tetracyclines by modification of a ribosomal lincosamide, streptogramin B resistance in gram-positives and protein). As mentioned above, in addition there is frequent methylation of 23S ribosome glycopeptides resistance in exchange of mobile elements containing resistance genes.enterococci is due to splitting of the end standing D-Alanyl from

N-acetyl-muraminic acid and replacing it by D-lactate.

An example for target modification reading to broad resistance

against antibiotics belonging to different compound classes is

the cfr-gene wwhich encodes methylation of 23S rRNA in MRSA are virtually resistant to all -lactam antibiotics. This is

posittion A2503 leading to resistance against flofenicol, based on formation of an additional penicillin-binding protein

chloramphenicol, linezolid, to macrolides, streptogramin B and (PBP2a) with low affinity for beta-lactams, which is coded by the

tiamulins in staphylococci. mecA gene. This determinant is cont5ained by chromosomal

located SCCmec elements. additional penicillin

binding protein PBP2a (low affinity to all beta lactam Methicillin-resistant Staphylococcus aureus (MRSA) are a

antibiotics) in methicillin resistant Staphylococcus aureus common cause of nosocomial infections worldwide. Hospital-

(MRSA) and coagulase negative staphylococci. associated MRSA (haMRSA) are often resistant to multiple

antibiotic classes, which limits treatment options. Since the end deletion, missense mutations in porin of the 1990s, however, MRSA infections in the general population genes in enterobacteriaceae (above alls Klebsiella spp.) and in without the risk factors known for acquisition of haMRSA have Pseudomonas aeruginosa leading to carbapenem resistance.been described, first in the USA and later worldwide.

specific porters (protein pump) Hospital associated MRSA is remarkable for its clonal pattern of conferring tetracycline resistance; ABC porters with expanded spread. There are 11 major MRSA clones within 5 groups of spectrum (extruding macrolides and streptogramines in related genotypes, they account for approximately 70 % of staphylococci and enterococci).>3,000 MRSA isolated obtained primarily from hospitals in the

United States, South America, and Europe. The major mover of ß-lactamases in all aerobic gram-negatives, in

this sort of clonal spread is thought to be infection control lapses staphylococci, Neisseria gonorrheae, Haemophilus influenzea,

by healthcare practitioners-physicians, nurses, or other persons aminoglycosides modifying enzymes in enterobacteriaceae,

who become colonized with S. aureus and then have contact with pseudomonads, staphylococci and enterococci (high level

hospitalized patients. MRSA, like any S. aureus, is known to resistance).

colonize the skin and particularly the anterior nares; such with low frequencies colonization may be transient or persistent, and may spread

(1 per 10-9 bacterial cells) resistance mutations occur in every faster during times of upper respiratory tract viral infections.natural population of bacteria.

In particular, fluoroquinolone resistance is a hallmark of Acquisition of other resistance mechanisms needs the nosocomial MRSA, although this was not always the case. When acquisition of resistance genes coding for them. Many resistance ciprofloxacin was first licensed, it was recommended as the first genes very likely originate from natural antibiotic producers orally administered treatment effective against MRSA. However, such as streptomycetes of from in bacteria which have to protect within 1 year many hospitals observed dramatic increases in the themselves against antibiotics in their natural micro ecological rate of ciprofloxacin resistance in MRSA. habitates such as soil.

For many years, vancomycin was the only effective treatment for Mobilization of resistance genes is mediated by integrons, serious MRSA infections. But in the past 6 years, 4 new agents insertion sequences, transposons, and finally plasmids. Via their with anti-MRSA activity have been introduced (quinupristin-59 base sequences integrons can accumulate several resistance dalfopristin, linezolid, daptomycin, and tigecycline). These new gene cassettes, thus forming multiresistance aggregates. The agents are most welcome, since the past decade has seen the same can be achieved by mobilization of resistance genes by emergence of vancomycin resistance in S aureus. insertions sequences and formation of multiresistance

Beside MRSA with intermediate susceptibility to vancomycin transposons which are known from both gram-positive and

(VISA) based on an altered cell metabolism acquisition of gram-negative bacteria. Via integrons and transposons

Target alteration due to mutation:

Target alteration due to modification:

Important examples for antibiotics resistant nosocomial

pathogens:

Methicillin-resistant Staphylococcus aureus (MRSA):

Synthesis of an alternative target:

Prevention of uptake:

Efflux of antibiotics:

Detoxification of antibiotics by hydrolysis or

modification:

Genetic events leading to resistance:

Prof. Dr. W. WitteRobert Koch-Institut, Bereich Wernigerode, Burgstraße 37, D-38855 Wernigerode, Tel.: 49 3943 679-246, Fax: 49 3943 679-

206, email: wittew@rki.de

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transferable vancomycin resistance from Enterococcus faecium resistance due to hydrolysis by plasmid encoded ß-lactamases

became a matter of special concern (so far 6 cases known from emerged. ß-lactamases in gram-negative bacteria can be grouped

the USA). according to their active site (figure 1). During the 1960ties and

1970ties most of ampicillin-resistant enterics produced class A -Community-associated MRSA (caMRSA) are usually less lactamases of type TEM-1, later of type SHV-1. About 10 years broadly resistant to antibiotics; they often contain the genes after the introduction of cefotaxim as the first 3rd generation lukS-PV lukF-PV coding for Panton-Valentine leucocidin (PVL) cephalosporin resistance this group cephalosporin which had been and SCCmec elements of types IV and V. Most of haMRSA are regarded as refractory to hydrolysis by -lactamases emerged. associated with 8 of the 10 major clonal lineages of the S. Surprisingly this was due to mutation(s) in TEM expanding the aureus population. caMRSA belong to various other clonal substrate spectrum. In TEM-derivatives of ESBL the site of the lineages than haMRSA. However, only a few of them are widely mutation decides about the hydrolysis spectrum with respect to disseminated and therefore can be regarded as epidemic. In the 3rd and 4th generation cephalosporines. Many amino acid USA, two lineages, namely multilocus sequence type (MLST) changes can lead to the ESBL phenotype, for most of them, ST1 ("USA400" according to the PFGE pattern) and ST8 however, complementory mutation in the enzyme protein age ("USA300"), are the most frequent and widely disseminated necessary for the stabilization of the protein structure.caMRSA. In Oceania, this is ST30 and in Europe St80.

Besides ESBL which have evolved from "classical" plasmid

encoded class A enzymes by mutations the CTX-M -lactamases Enterococci are

are particularly interesting as they originate from chromosomale commensal bacteria of the animal and human gut but con also

blactxM-genes which are naturally chromosomal located in serve as dreaded nosocomial pathogens of life-threatening

Kluyvera spp., a enterobacterial species for which plants are the infections especially among the elderly, immuno-compromised

natural habitate captured by an insertion sequence they are or seriously ill patients. E. faecalis still earmarks the majority of

integrated into broad host range plasmids.enterococcal infections, mostly urinary tract infections,

endocarditis and bacteraemia. However, E. faecium attracts Besides a few enterobacterial species such as Klebsiella spp. the more and more attention due to its capacity of acquiring genomes of enterobacteria contain the ampC gene coding for a multiple antibiotic resistance determinants, especially those cephamycinase mediating broad spectrum cephalosporin encoding glycopeptide resistance and its potential to spread resistance. The gene is normally reposed and only in a few species among the nosocomial setting. The population structure of E. with an efficient promoter (Citrobacter spp., Enterobacter spp.), faecium has been disclosed by methods like amplified-fragment here constitutive mutants express clinically significant length polymorphism (AFLP), multi-locus sequence typing cephalosporin resistance. Via integrons of class I ampC genes can (MLST) and most recently comparative genomic hybridizations. be mobilized and integrated into plasmids and widely Within the clonal complex (CC) of human isolates a distinct disseminated (mobilized ampC).subcluster (CC17 or C1) was identified by all these methods

combining strains from clusters of infections and outbreaks

among hospital patients from a representative worldwide The worldwide emergence of MRSA as a nosocomial pathogen and

collection. Characteristics of those so-called hospital-adapted, more recently also in the community followed by broad recently

epidemic-virulent clonal types are, based on logistic regression also in the community followed by broad resistance in gram-

models, (i) ampicillin resistance, (ii) high-level fluoroquinolone negative pathogen to all -lactamases currently available poses a

resistance, and (iii) possession of virulence markers. threat to public health.

Dissemination of isolates representing epidemic clonal types of Rational use of antibiotics thus reducing selective pressure in the MLST CC-17 complex among the hospital setting possessing favour of resistance and target infection control measures for the above mentioned features and acquisition of determinants prevention of further dissemination have to be brought into place.encoding vancomycin resistance as an indicator, to a later stage

became a problem in hospitals world-wide. Furthermore, there is an urgent need for development new

antibacterial compounds refractory to resistance mechanisms Class B lactamases (preferentially of the VIM and the IMI types) bacteria have acquired so far.at first became known from Pseudomonas aeruginosa and in

Acinetobacter spp. Already in the mid 1990ties in South East

Asia and later in South-East Europe. The corresponding genetic

determinants were contained by class 1 integrons which more

recently became integrated into broad host range plasmids and

disseminated to Klebsiella pneumoniae with broad resistance to

other antibiotics. This has lead to the emergence of isolates

only susceptible to colistin in Central Europe and isolates

completely resistant to all antibiotics in Greece.

The base mechanism

conferring resistance against this classes of compounds are -

lactamases, the classification of these enzymes according to

the active center of these enzymes is shown in figure 1. Most of

the class A enzymes and class D enzymes represent the

"classical" plasmid encoded enzymes, the gene(s) for class C

enzymes are naturally contained in the core genome of nearly

all enterobacteriaceae; class B enzymes are metallo--

lactamases also capable of hydrolysis carbapenem. 1. Tenover FC. 2001. Development and spread of bacterial

. Soon resistance to antimicrobial agents: an overview. Clin Infect

after the introduction of ampicillin into human chemotherapy Dis. 33 Suppl 3:S108-15.

Glycopeptide-resistant enterococci:

Conclusion:

Gram-negative bacteria with brad resistance against

cephalosporines and carbapenems:

References:

Extended spectrum ß-lactamases in enterobacteriaceae

Fig. 1 Classification of ß-lactamases

β Laktamases

Active center Serin Metallo(Zn2+)

Classification according to Amber

A C D B

Inhibition by clavulanic acid (Cefpodoxim)

+ - + -

Hydrolysis by Cefpoxitin - + - - Inhibition by EDTA - - - - Examples TEM

SHV-1 CMY-2

PAO OXA IMP

VIM

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2. Amabile-Cuevas CF (ed.). 2003. Multiple drug-resistant 8. Andersson DI. 2006. The biological cost of mutational

bacteria. 1st edition, Horizon scientific press, Norforlk, UK. antibiotic resistance: any practical conclusions? Curr Opin

Microbiol. 9: 461-5.3. Hall BG. 2004. Innovation: Predicting the evolution of

antibiotic resistance genes. Nature Reviews Microbiology 2, 9. D'Costa VM, McGrann KM, Hughes DW, Wright GD. 2006.

430-435. Sampling the antibiotic resistome. Science 311: 374-7.

4. Kumar A, Schweizer HP. 2005. Bacterial resistance to 10. Piddock LJ. 2006. Clinically relevant chromosomally encoded

antibiotics: active efflux and reduced uptake. Adv Drug multidrug resistance efflux pumps in bacteria.Clin Microbiol

Deliv Rev. 57: 1486-513. Rev. 19: 382-402.

5. Lambert PA. 2005. Bacterial resistance to antibiotics: 11. Depardieu F, Podglajen I, Leclercq R, Collatz E, Courvalin P.

modified target sites. Adv Drug Deliv Rev. 57: 1471-85. 2007. Modes and modulations of antibiotic resistance gene

expression. Clin Microbiol Rev. 20: 79-114. 6. Wright GD. 2005. Bacterial resistance to antibiotics:

enzymatic degradation and modification. Adv Drug Deliv 12. Woodford N, Ellington MJ. 2007. The emergence of antibiotic

Rev. 57: 1451-70. resistance by mutation. Clin Microbiol Infect. 13: 5-18.

7. Woodford N. 2005. Biological counterstrike: antibiotic 13. Baquero F, Nombela C, Cassell GH, Gutierrez-Fuentes JA

resistance mechanisms of Gram-positive cocci. Clin (eds.). 2008. Chapter III: Evolutionary biology of drug

Microbiol Infect. 11 Suppl 3:2-21. resistance. In: Evolutionary biology of bacterial and fungal

pathogens. ASM Press, Washington, DC, USA.

National Antibiotic Policy in The Context of India

Introduction

Need of antibiotic policy in India

Conclusion

policy, clinicians, pharmacists and key decision-makers are

required to be clear on the ways to make plans for evaluating its Antibiotics are one of the most widely used classes of drugs in impact. It is also important to know the patterns of antibiotic the world, accounting for over 25% of drug costs in many prescriptions and the surveillance about the prevalence of hospitals and for a higher proportion of prescriptions in the resistant strains in order to improve patient care. There is, community, especially in the developing world. Many studies however, lack of such surveillance data from India because there about the use of antibiotics from various countries, both is no large scale, meta-analytic studies in India. Another serious developing and developed, have highlighted the widespread concern is the lack of any strict adherence to the standard or inappropriate use of antibiotics. Antibiotic resistance is the recommended procedures in the microbiology laboratories major cause of morbidity and mortality worldwide. It is the across the country performing antibiotic susceptibility tests. This cause of increased healthcare cost. It should be prevented as gives rise to different and inadequate performance and results.much as possible or detected as soon as it emerges in order to

prevent the spread of resistant strains. For the prevention and The practice of indiscriminate dispensing antibiotics over the

detection of resistance, a need of rational antibiotic therapy is counter without any licensed prescriptions is another important

obvious and national policies or guidelines to address this issue that has to be critically addressed in India. Though an

issue are required. For the appropriate prescription and use of infection control committee exists in the hospitals of India, but

antibiotics, it is necessary to develop antibiotic policy. The aim of the infection control committee is inactive and exists only in

the policy is to improve the quality of prescribing leading to paper work just for a name. At the times of serious outbreaks of

reduction of resistance and cost, and improvement in patient infection, this committee becomes a little bit active but the

care. The antibiotic policy addresses to improve patient care by common cause of this outbreak is due to the unconcern towards

promoting the best practice in antibiotic prophylaxis and infection control in the first place. In the mid-1990s, the use of

therapy, to make better use of resources by using cheaper drugs expired or 'resterilised' disposables such as intravenous infusion

wherever possible, to retard the emergence and spread of sets and catheters in a government hospital in New Delhi led to a

multiple antibiotic-resistant bacteria, to improve education of serious outbreak of septicaemia that killed 26 people. In spite of

junior doctors by providing guidelines for appropriate therapy, to such outbreaks, few, if any, Indian government hospitals have

eliminate the use of unnecessary or ineffective antibiotics and to policies for using antibiotics, and they do not have an antibiotic

restrict the use of expensive or unnecessary ones. monitoring system.

With the type of resistance patterns prevailing, there is an

absolute and urgent need for nationwide-specific and standard-

operating guidelines for the performance of antibiotic high-end Information on the antibiotic resistance pattern of bacterial

susceptibility tests that should be strictly implemented in all isolates is still not known in developing countries because the

laboratories across the country. facilities for routine susceptibility testing are rare and limited to

a few laboratories. Like most developing countries, India also

lacks a national policy or guidance on the use of antibiotics.

Developing national policies is vital to combat the rise of Hence at the growing risk of antibiotic resistance worldwide, it resistance. Before getting on upon the development, has been extremely important for development of antibiotic dissemination and subsequent implementation of an antibiotic policy in India in order to prevent further spread of resistance and

Arati Sharma, BPharm,Sankaralingam Bhuvaneswari College of Pharmacy, Tamilnadu, India

Antibiotic resistance is largely due to inappropriate use of antibiotics. The use of antibiotics is related to the prescription of antibiotics

and self medication to some part. In order to reduce the resistance of antibiotic, hence, it is important to develop and follow antibiotic

policy. In India, due to lack of national antibiotic policy, antibiotic resistance is one of the major problems for immature deaths. So, it

is of utmost necessity to develop a national antibiotic policy in India and implement it to prevent and fight with antibiotic resistance.

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treating the resistance in an isolated environment. To control Publications Division, Issue dtd. 1st to 15th June 2005

the overuse, inappropriate prescription and early abandon of 3. El-Azizi M, Mushtaq A, Drake C, Lawhorn J, Barenfanger J, therapy, a national antibiotic policy should be developed in Verhulst S, et al . Evaluating antibiograms to monitor drug India. Such measures require political will, government resistance. Emerg Infect Dis; 2005;11:1301-2commitment and significant levels of funding. Nevertheless,

4. Binyon D. and Cooke RPD. Restrictive antibiotic policies - how without these measures, the threat of antibiotic resistance in

effective are they? Hospital Pharmacist, 2000; 7: 183-187developing countries could grow uncontrolled.

5. Lakshmi V. Need for national/regional guidelines and policies

in India to combat antibiotic resistance. Indian Journal of

Medical Microbiology ;2008; 26: 105-1071. Smith A J, Aronson JK, and Thomas M. Antibiotics policies in

6. Seth P. Antibiotic resistance calls for better diagnostic labs. the developing world. Eur J Clin Pharmacol,1991; 41:85-87Science and Development Network. 26 March 2008

2. Joshi MC, Tariq K, Ejaj A. Restricted antibiotic policy:

Rational approach towards antibiotic resistance - Policy -

Express Healthcare Management. Indian Express, Business

References:

Preventing Antimicrobial Resistance: Role of Pharmacy Students

Introduction

Role of pharmacy students

The discovery series of antimicrobials began with the accidental To check the occurrence of resistant microorganisms, there is a

finding of penicillin by Alexander Fleming in 1929. Then it was need of better education of the public, doctors, pharmacists and

introduced into clinical medicine by Florey, Chain and associates veterinarians in the appropriate use of the drugs. The

at Oxford University in 1941. The antimicrobial agents were antimicrobial use for inappropriate indications should be

subsequently developed by Prof. Selman Waksman of Rutger restricted, existing laws regarding over-the-counter drugs should

University by discovering Streptomycin in 1944. Then be made strong to ensure rational sale and use of antimicrobials;

chlortetracycline, macrolides and many other antimicrobials judicious use of antimicrobials in hospitals should be done by

were introduced into the arena of pharmacotherapeutics. intensive teaching of the principles of the use of antimicrobials

However, being useful class of drugs, they are also leading and to establish better control measures for nosocomial

group of widely misused drugs. The most important infections.

contributing factors of misuse are the complicated mode of

diagnosis and prescribing for the prevention and treatment of

infectious diseases. Pharmacy students can contribute to the prevention and control

Resistance to antimicrobials is currently a major health concern of antimicrobial resistance. In the present context, antimicrobial

in treating infectious diseases because many bacteria that resistance needs a great attention and many researches are being

cause infections are becoming resistant to commonly-used conducted by scientists, antimicrobial usage guidelines are being

antimicrobials leading to treatment failure. Antibiotic formulated and many programmes for awareness are being

resistance is very much annoying, troublesome and costly for carried out to which pharmacy students can add a brick.

the general public and also imparts a serious problem in the With such a noble purpose that pharmacy students can be therapeutics. The problems of such resistance have been found competent and knowledgeable regarding various aspects of in case of tuberculosis, malaria, typhoid, etc. and many other pharmacotherapeutics like preventing or minimizing drug resistant cases are also emerging especially in developing antimicrobial resistance problem, many universities and schools and under-developed countries. The rise of many resistant of pharmacy have incorporated Doctor of Pharmacy (Pharm D) strains like Methicillin resistant Staphyloccus aureus (MRSA), program in their curricula. Likewise, some colleges have Vancomycin-intermediate Staphylococcus aureus (VISA) and introduced Masters in Clinical Pharmacy or Pharmacology or Vancomycin resistant Staphyloccus aureus (VRSA), Extended Pharmaceutical Care. Moreover, many universities are now spectrum beta lactamase (ESBL) producing enterobacteria like running Bachelor of Pharmacy program giving more preference to Escherichia coli , multi drug resistant Pseudomonas aureginosa pharmacotherapy.has given a scarcity for the effective antimicrobials and

Students, by conducting campaigns, workshops and carrying out scientists are exploring new ways to search new antimicrobials

small scale studies about the pattern of prescription and and methods to prevent the emergence of resistance in the first

susceptibility, most prevalent strain in a particular area, place.

patient/physician satisfaction, the habit of people to self-Various factors contribute to antimicrobial resistance, some of medicate antimicrobials etc. can help to know the status and which are the use of antimicrobials in animal feeds in low doses, ultimately to prevent the development and to improve the availability of antimicrobials over-the-counter in many treatment of antimicrobial resistance. countries, misuse by health professionals, poor patient

They can carry out public awareness campaigns regarding the compliance, antimicrobial application in agriculture, aquaria

antibiotics resistance problem via media (radio, television), and family pets and eating raw or undercooked foods. The most

seminars, role-play, drama, conducting talk programmes, notable causes are improper antimicrobial use and

marching in some rally and interacting with other health sector inappropriate empiric therapy selection.

4

Atmika Paudel, MPharm, University of Tokyo, JapanBinaya Sapkota, BPharm, Tribhuvan University, Nepal

Antimicrobial resistance is a global problem that requires attention. There are several approaches to prevent the spread of resistant

strains. Pharmacy students can play a vital role in combating resistance. Together with other organizations, pharmacy students'

organizations, both national and international, can contribute to prevent and combat antimicrobial resistance by conducting various

programmes. This article has summarized the roles that pharmacy students can play in reducing this growing problem.

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colleagues etc. They can develop and distribute pamphlets and students and evaluating and promoting a pharmacy school

other educational materials to promote the appropriate curriculum on appropriate use of antimicrobials, forming

antimicrobial use and importance of completion of therapy for partnerships to harness the resources of collaborating

preventing emergence of resistance. Such programmes will not organizations and conducting research in the field of

only create and increase the awareness of general public about antimicrobials.

the importance of judicious use of antimicrobials, prevention of

self medication of such medicines but also make the pharmacy 1. Nicholas WK. Remington: The Science and Practice of

students more competent and prepare themselves to handle Pharmacy 20th edition: Lippincott Williams & Wilkins, USA,

their responsibilities when they become pharmacists.2000; 87(2): 1514.

2. Barriere SL. Pharmacotherapy: A Pathologic Approach 3rd

edition: Appleton & Lange, USA, 1997; 98(3): 1953- 1969

Pharmacy students are one of the potential members, who can 3. Essential Drugs Monitor No. 28-29 (2000). WHO/DAP, help in reducing the morbidity and mortality caused by WHO/EDM; 2000 antimicrobial resistance. They can make a difference by

4. Tenover FC. Mechanisms of Antimicrobial Resistance in conducting different programmes that draw attention of

Bacteria. The American Journal of Medicine .2006; 119 (6A), community as well as health care professionals. International

S3S10Pharmaceutical Students Federation (IPSF) is playing a crucial

5. Weller TMA and Jamieson CE. The expanding role of the role in raising awareness about many health related issues by antimicrobial pharmacist. Journal of Antimicrobial conducting several programmes and campaigns and by Chemotherapy, 2004; 54: 295298publishing newsletters, bulletins and supplements. It can

further act in combating antimicrobial resistance by assessing

the knowledge about antimicrobial resistance among pharmacy

References:

Conclusion

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International Pharmaceutical Students' Federation

P.O. BOX 842002508 AE Den HaagThe Netherlands

Tel: +31 70 302 1992Fax: +31 70 302 1999

E-mail: ipsf@ipsf.orgWebsite: www.ipsf.org