Approaches to reduce antibiotic resistance in the community.
ABSTRACT During the last two decades, there has been an alarming worldwide increase of resistance to antibiotics of bacterial pathogens responsible for community-acquired infections. This dramatic evolution is generally attributed to the extensive use of antibiotics and the selective pressure on the bacterial strains. To decrease antibiotics resistance in the community, several approaches should be considered through: reducing unnecessary antibiotic prescriptions: inappropriate antibiotic treatments are becoming a major issue; however, few studies have shown a decrease of antibiotic resistance following a reduction of antibiotic use in the community;decreasing the prescriptions of the more selective antibiotic compounds for some bacterial species, eg macrolides and group A streptococcus (GAS), trimethoprim-sulfamethoxazole and pneumococcus; using an optimal dosage and duration of antibiotic regimens chosen; some studies have suggested that low dosage and long treatment duration could promote antibiotic resistance; and implementing the pneumococcal conjugate vaccines; several studies have shown a decline in the proportion of penicillin nonsusceptible Streptococcus pneumoniae isolated from invasive pneumococcal diseases or nasopharyngeal flora. The combination of these approaches, particularly the reduction of antibiotic use and pneumococcal immunization, could be synergistic.
- SourceAvailable from: Francesca Collu[Show abstract] [Hide abstract]
ABSTRACT: Over-expression of multidrug efflux pumps of the Resistance Nodulation Division (RND) protein super family counts among the main causes for microbial resistance against pharmaceuticals. Understanding the molecular basis of this process is one of the major challenges of modern biomedical research, involving a broad range of experimental and computational techniques. Here we review the current state of RND transporter investigation employing molecular dynamics simulations providing conformational samples of transporter components to obtain insights into the functional mechanism underlying efflux pump-mediated antibiotics resistance in Escherichia coli and Pseudomonas aeruginosa.Computational and structural biotechnology journal. 01/2013; 5:e201302008.
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ABSTRACT: Infectious diseases are known as one of the most life-threatening disabilities worldwide. Approximately 13 million deaths related to infectious diseases are reported each year. The only way to combat infectious diseases is by chemotherapy using antimicrobial agents and antibiotics. However, due to uncontrolled and unnecessary use of antibiotics in particular, surviving bacteria have evolved resistance against several antibiotics. Emergence of multidrug resistance in bacteria over the past several decades has resulted in one of the most important clinical health problems in modern medicine. For instance, approximately 440,000 new cases of multidrug-resistant tuberculosis are reported every year leading to the deaths of 150,000 people worldwide. Management of multidrug resistance requires understanding its molecular basis and the evolution and dissemination of resistance; development of new antibiotic compounds in place of traditional antibiotics; and innovative strategies for extending the life of antibiotic molecules. Researchers have begun to develop new antimicrobials for overcoming this important problem. Recently, platensimycin - isolated from extracts of Streptomyces platensis - and its analog platencin have been defined as promising agents for fighting multidrug resistance. In vitro and in vivo studies have shown that these new antimicrobials have great potential to inhibit methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae by targeting type II fatty acid synthesis in bacteria. Showing strong efficacy without any observed in vivo toxicity increases the significance of these antimicrobial agents for their use in humans. However, at the present time, clinical trials are insufficient and require more research. The strong antibacterial efficacies of platensimycin and platencin may be established in clinical trials and their use in humans for coping with multidrug resistance may be allowed in the foreseeable future.Infection and Drug Resistance 01/2013; 6:99-114.
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ABSTRACT: We compared uropathogen antibiotic susceptibility across age groups of ambulatory pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods (n=626), significant differences (p<0.05) existed across age groups for ampicillin, cefazolin, and trimethoprim/sulfamethoxazole susceptibility. In E. coli, differences in trimethoprim/sulfamethoxazole susceptibility varied from 79% in children under 2 to 88% in ages 16-18 (p<0.001) while ampicillin susceptibility varied from 30% in children under 2 to 53% in ages 2-5 (p=0.015). Uropathogen susceptibility to common urinary anti-infectives may be lower in the youngest children. Further investigation into these differences is needed to facilitate appropriate and prudent treatment of urinary tract infections.Journal of pediatric nursing 09/2013; · 0.92 Impact Factor
Approaches to Reduce Antibiotic Resistance in
Robert Cohen, MD
Abstract: During the last two decades, there has been an alarming
worldwide increase of resistance to antibiotics of bacterial patho-
gens responsible for community-acquired infections. This dramatic
evolution is generally attributed to the extensive use of antibiotics
and the selective pressure on the bacterial strains. To decrease
antibiotics resistance in the community, several approaches should
be considered through:
reducing unnecessary antibiotic prescriptions: inappropriate antibiotic
treatments are becoming a major issue; however, few studies
have shown a decrease of antibiotic resistance following a
reduction of antibiotic use in the community;
decreasing the prescriptions of the more selective antibiotic com-
pounds for some bacterial species, eg macrolides and group A
streptococcus (GAS), trimethoprim-sulfamethoxazole and pneu-
using an optimal dosage and duration of antibiotic regimens chosen;
some studies have suggested that low dosage and long treat-
ment duration could promote antibiotic resistance; and
implementing the pneumococcal conjugate vaccines; several studies
have shown a decline in the proportion of penicillin nonsuscep-
tible Streptococcus pneumoniae isolated from invasive pneumo-
coccal diseases or nasopharyngeal flora.
The combination of these approaches, particularly the reduction of antibi-
otic use and pneumococcal immunization, could be synergistic.
Key Words: antibiotic resistance, antibiotic prescriptions,
pneumococcal conjugate vaccine
(Pediatr Infect Dis J 2006;25: 977–980)
the last 2 decades.1,2The clinical impact of antibacterial
resistance is evident from an increasing number of clinical
failures reports.3–5This antibiotic resistance phenomenon
involves not only respiratory pathogens as Streptococcus
pneumoniae, group A streptococcus (GAS) or Haemophilus
influenzae but also agents responsible for urinary, digestive,
or cutaneous infections as Escherichia coli, Shigella sonnei
he prevalence of antibacterial resistance among commu-
nity-acquired pathogens has increased dramatically over
or Staphylococcus aureus.1Furthermore, bacterial resistance
to multiple antibacterial agents is rapidly becoming a world-
wide problem as it may limit treatment options.1
This dramatic evolution of resistance should lead to very
serious problems in a few years, particularly because most big
pharmaceutical companies have stopped the research of new
compounds, tying in with the problems created by antibiotic
companies are that the market becomes unattractive due to the
prospective restriction of antibiotic use, the relatively few pa-
tients involved and the shortened treatment durations.
To reduce this worrying trend, I suggest several ap-
proaches: reducing unnecessary antibiotic prescriptions, pre-
scribing the less selective antibiotic regimens, and, finally,
promoting implementation of vaccines, particularly pneumo-
coccal conjugate vaccines (PCV).
REDUCING UNNECESSARY ANTIBIOTIC
Several studies have shown higher rates of antibiotic
resistance in high-antibiotic-consuming countries.6On an
individual level, antibiotic use has been linked to an increased
risk of harboring or becoming infected with antibiotic-resis-
tant bacteria.7–9Misuse of antibiotics for viral upper respira-
tory tract infections has been well documented, with high
prescribing rates.10,11In many countries where the consump-
tion is high, the question is not if we have to limit the
antibiotic prescriptions but how, and if the reduction of
antibiotic use can decrease the antibiotic resistance. Although
examples of a correlation between resistance and antibiotic
usage have been reported, not all studies have shown sus-
tained decrease in pneumococcal resistance with declining
To reduce antibiotic prescriptions and, consequently,
antibiotic consumption, multifaceted educational programs to
promote more prudent use of antibiotics must be imple-
mented, involving physicians and other health care workers
and also consumers of care (patients, parents).12–14In fact, it
has been demonstrated that, on one hand, parental pressure for
on the other hand, that programs involving only parental edu-
cational intervention have little or no effect.15Programs for
physicians and parents have to include two key points:
1. tools to help physicians to reduce diagnostic uncertainty
2. reassurance that reduction of antibiotic use is not linked to
an increase of severe bacterial diseases
Tools to Reduce the Diagnostic Uncertainty. The diagnostic
uncertainty increases the prescriptions of antibiotic treat-
From the Department of Microbiology, Centre Hospitalier Intercommunal de
Cre ´teil, Cre ´teil, France.
Address for correspondence: Robert Cohen, MD, Department of Microbiol-
ogy, Centre Hospitalier Intercommunal de Cre ´teil, 40 Avenue de Verdun,
94010, Cre ´teil Cedex, France. E-mail: Robert.email@example.com.
Copyright © 2006 by Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 25, Number 10, October 2006
ments.16Tools to reduce the diagnostic uncertainty include
the establishment of national or local guidelines, their disper-
sion, and an improved training of primary care physicians,
particularly for general practitioners. Furthermore, the imple-
mentation of rapid diagnostic tests could help. In many
countries, most patients suffering from pharyngitis receive
antibiotic treatments only on the basis of clinical signs and
symptoms. Most pharyngitis is caused by viruses, and GAS is
the only cause that currently merits antimicrobial treatment.
The main consideration in managing pharyngitis is to deter-
mine who has GAS pharyngitis to institute appropriate anti-
biotic therapy and who does not have strep infection and
therefore does not need antibiotic treatment. Scoring systems
can reduce antibiotic usage but are insufficiently sensitive and
specific. If throat culture is the gold standard, rapid antigen
tests (RAT) have been improved. In the “real world,” analysis
of office performance of throat cultures and RAT suggests
little difference in accuracy. In fact, in the office or emer-
gency setting, there may be little benefit to confirming neg-
ative RAT with throat cultures in areas with little or no acute
rheumatic fever. In Slovenia and France, the implementation
of RAT in the last years has been followed by significant
reduction of antibiotic use.17,18In Slovenia, there was a
negative correlation between the number of RAT and antibi-
otic use (r ? ?0.68).17
Other rapid diagnostic tests could have a positive im-
pact on the reduction of antibiotic use. Because of increasing
pressure to use antibiotics only for proven bacterial diseases,
diagnosis of viral illness becomes more paramount. Several
studies have shown that patients with documented influenza
infection have fewer antibiotics administered, thus reducing
indiscriminate antibiotic use in proven viral illness.19–21Bon-
ner et al21recently have shown that the use of rapid diagnos-
tic test kits for influenza could lead to a clear reduction of
antibiotic use in the pediatric emergency setting.
Furthermore, in Slovenia, there was a negative corre-
lation between the number of C-reactive protein tests and
antibiotic consumption (r ? ?0.73).17
Reduction of Antibiotic Use and Alleged Increase of Severe
Bacterial Diseases. If some data have suggested an associa-
tion between reduced prescribing and an increased incidence
of rare complications of bacterial infection,22,232 studies,
published this last year, provide confirmation.17,24
The first one, by Cizman et al17in Slovenia, has shown
that the reduction of antibiotic use during the last 5 years has
not induced an increasing rate of mastoiditis. The second one,
by Sharland et al,24has reported, over the past decade in
England, that antibiotics’ use has halved and that this reduc-
tion has not been associated with an increase in admission to
the hospital for peritonsillar abscess or rheumatic fever. In the
same study, data on mastoiditis and simple mastoidectomy
are conflicting: apparent increase in hospital events and
reduction in general practice.
USE OF LESS SELECTIVE ANTIBIOTIC
Antibiotic Compounds. Higher potential to promote carriage
of antibiotic resistant Streptococcus pneumoniae has been
suggested for macrolides (particularly azithromycin), tri-
methoprim-sulfamethoxazole and oral cephalosporins, com-
pared with penicillins.25,26Significant association has been
also suggested between temporal and regional erythromycin
resistance in S pyogenes and consumption of macrolides.27,28
However, the ability of any drug to promote carriage of
resistant strains depends on the prevalence of resistance in the
community: when the prevalence of resistance in the com-
munity is absent or low, it is difficult to demonstrate an
increase of resistance in individuals who receive a drug; when
the levels of resistance are intermediate, selection-pressure
phenomenon becomes more easily apparent; ultimately, the
effect can be masked in areas where resistance is high.
Optimal Dosage and Duration of Antibiotic Regimens. Three
studies, at least, have shown that low dosage and/or long
treatment duration increase the risk of carriage of resistant
strains. Guillemot et al,28in a prospective observational
study, have suggested that carriage of penicillin nonsuscep-
tible pneumococci (PNSP) was associated with low daily
doses of oral ?-lactam (OR, 5.9; 95% CI, 2.1–16.7) and long
(?5 days) treatment duration (OR, 3.5; 95% CI, 1.3–9.8).
Schrag et al29in prospective randomized study comparing
amoxicillin 90 mg/kg per day for 5 days and 40 mg/kg per
day for 10 days have shown that the risk of PNSP carriage
was lower at 1 month in the short-course, high-dose group
(24%) compared with the standard-course group (32%) (P ?
0.03) (RR,0.77; 95% CI, 0.60–0.97).
Our group has published a few years ago a study
comparing 2 azithromycin dosages: the 20 mg/kg/d dose of
azithromycin has had a better effect than the 10 mg/kg/d dose
in terms of minimizing the risk of emerging resistance in the
GAS.30Using the molecular tools restriction fragment length
polymorphism and random amplified polymorphic DNA, we
found 8 cases of bacteriologic treatment failure with geneti-
cally related strains that had increased azithromycin MICs
after treatment with 10 mg/kg/d azithromycin. This phenom-
enon did not occur with the 20 mg/kg/d azithromycin for a
Several vaccines may contribute to reduction of opportu-
nities to prescribe antibiotic treatments: eg pertussis, varicella,
and certainly influenza vaccine. Neuzil et al31have shown in
Tennessee that for every 100 children, an annual average of 3 to
9 courses of antibiotics was attributable to influenza.
Furthermore, reductions of 25% in antibiotic use for
influenza-associated illnesses32and of 41%–45% in days of
antibiotic use33have been reported after influenza vaccination.
However, the most promising are the PCVs. In fact,
these vaccines can reduce the antibiotic prescriptions and
have a direct effect on pneumococcal resistance. There is
evidence suggesting that the use of these conjugate vaccines
will reduce the need for antibiotics and the subsequent spread
of antibiotic-resistant pneumococci. Dagan et al34have
shown that PCVs reduce occurrence of respiratory infections
and antibiotics’ use in daycare-center attendees. Because
pneumococcus is the leading cause of bacteremia in young
febrile children, it should be emphasized that the risk of
The Pediatric Infectious Disease Journal • Volume 25, Number 10, October 2006
© 2006 Lippincott Williams & Wilkins
invasive bacterial infection has reduced due to the use of
PCV. Routine vaccination with PCV should be accompanied
by supportive education of more restricted use of antibiotics.
Numerous studies have shown that PCVs reduce the
nasopharyngeal carriage of vaccine serotypes. This vaccine
may then reduce the prevalence of antimicrobial-resistant
pneumococci among vaccinated children and their contacts35
because the vaccine-type strains represent the majority of
antibiotic-resistant strains. Others studies have shown a de-
cline in the proportion of PNSP isolated from invasive pneu-
mococcal disease after the implementation of PCV immuni-
Recently, our group has shown in France that the imple-
mentation of PCV combined with a reduction in antibiotic use,
in a country with a high prevalence of antibiotic-resistant pneu-
mococci, appears to have a strong impact on the carriage of
highly penicillin-resistant pneumococcus (HPRP).37To follow
the Sp serotypes and antibiotic resistance trends after the imple-
mentation of PCV, a national prospective surveillance network
was set up after September 2001. French pediatricians were
recruited to carry out nasopharyngeal swabs in infants and
toddlers suffering from AOM. Over the 3-year survey, 1906
patients were enrolled. The percentage of PCV-vaccinated chil-
61.4% (third year). Antibiotic usage within 3 months before
enrollment has been reduced from years 1 to 3, respectively:
51.5%, 44.5%, 40.7%. The risk for a child to carry HPRP was
4.2% (95% CI, 3.3%–5.1%) for children immunized and who
had not received antibiotic treatment within 3 months before
enrollment, 8.6% (95% CI, 7.4%–9.9%) for those vaccinated
and who had received antibiotic treatment, 10.3% (95% CI,
8.9%–11.7%) for children not immunized and who had not
received antibiotic treatment, and 16.2% (95% CI, 14.5%–
17.9%) for children not vaccinated and who had received anti-
biotic treatment during the same period. However, pneumococci
can undergo capsular serotype switching; therefore, the potential
exists for a vaccine-serotype clone that is resistant to an antibi-
otic to switch its capsule to a nonvaccine serotype and hence
evade the protective effects of PCVs.38,39These observations
underscore the importance of ongoing surveillance of Strepto-
coccus pneumoniae isolates.
To reduce antibiotic resistance in the community, ap-
proaches have to be combined. Reduction of unnecessary
antibiotic prescriptions, combined with the implementation of
PCVs, is probably the most efficient strategy. In addition,
prescription of the less selective antibiotic compounds and
use of optimal dosage and duration must be recommended.
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The Pediatric Infectious Disease Journal • Volume 25, Number 10, October 2006
© 2006 Lippincott Williams & Wilkins