a drogas antimicrobianas
J Manag Care 2000 Dec;6(23 Suppl):S1197-201
Is drug resistance affecting treatment outcomes?
Antimicrobial drug resistance is a growing concern for the medical
community.Although cases of drug resistance to Streptococcus pneumoniae
are on the increase, there has been no change in mortality rates. The fact
that the medical literature shows no proven correlation between
drug-resistant S pneumoniae and clinical failure suggests that concerns
about drug resistance in S pneumoniae may be overstated. Therefore, in
treating community-acquired pneumonia, physicians should also weigh other
important considerations such as pharmacology, safety, tolerability, and
Am J Manag Care 2000 Dec;6(23 Suppl):S1178-88
Clinical choices of antibiotics: judging judicious use.
Scientific literature widely documents the current overuse of antibiotics
but often does not address the issue of the judicious use of antibiotics.
Multiple analyses of prescribing patterns consistently reveal
inappropriate prescribing of antibiotics, even when the clinician is aware
of appropriate antibiotic use. In addition to overprescribing antibiotics,
providers frequently address therapy failures by switching to same-class
antibiotic agents. Additional investigations report that prescribing of
antibiotics at the first office visit tends to increase, rather than
decrease, costs and has marginal impact on patient outcomes. Patient
education interventions, delivered prior to illness, can significantly
reduce inappropriate use of antibiotics and reverse resistance trends. A
variety of developments in antimicrobial use and resistance and newer
antibiotic and respiratory infection management strategies are discussed.
Int J Antimicrob Agents 2001 Jan;17(1):21-6
Resistance to antimicrobial agents in Mediterranean countries.
Gur D, Unal S
Director of Hacettepe University, Children's Hospital, Clinical
Microbiology Laboratory, 06100, Ankara, Turkey. firstname.lastname@example.org
Int J Antimicrob Agents 2001 Jan;17(1):9-19
Quality measures of antimicrobial drug use.
Department of Medical Microbiology and Infectious Diseases, Erasmus
University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam,
The Netherlands. email@example.com
Antimicrobial use is the major determinant in the development of
resistance. Many parameters of importance for optimal quality of
antimicrobial therapy have already been defined. Maximal efficacy of the
treatment should be combined with minimal toxicity at the lowest cost.
Quality of antimicrobial drug use is dependent on knowledge of many
aspects of infectious diseases. Considering efficacy, many of our
indications for antimicrobial use need critical evaluation. Irrational use
should be discouraged. Avoidance of the development of resistance is a
quality parameter that will need increasing attention. This paper reviews
the well-established factors that may influence the appropriateness of
pharmacotherapy with antimicrobial drugs. It cites recent evidence
supporting principles of prudent prescribing and gives an overview of
audits that have addressed these parameters. Measures relating to
resistance are discussed.
Int J Antimicrob Agents 2000 Nov;16(3):191-7
Development and persistence of multi-resistance to antibiotics in
bacteria; an analysis and a new approach to this urgent problem.
van der Waaij D, Nord CE
University of Groningen, Groningen, The Netherlands.
The intestinal microflora may have more influence on infectious diseases,
than the mere control of growth of opportunistic micro-organisms by
colonisation resistance (CR) and unspecific stimulation of the immune
system. In compromised patients the CR may become decreased for several
reasons but mostly because antibiotics reach the intestine during
treatment. The consequence of a CR-decrease is that antibiotic-resistant
opportunistic micro-organisms may increase in numbers in the gut. In this
context, it is hypothesised that if the CR could be maintained at a normal
level, the risk for maintenance and spread of resistant strains could be
mitigated. Such maintenance requires absence of active antibiotic
substance in the gut. This might be brought by the inactivation of
antimicrobial agents by intestinal contents. Intra-intestinal inactivation
has been described to occur along two possible routes: (1) inactivation by
chemical binding or absorption and (2) by enzymatic destruction. Secondly,
the composition of the intestinal microflora should be maintained at a
normal level in case of other reasons for CR-decrease than antibiotic
activity. Comprehensive study of the composition of normal microflora and
the strains of species which play a role in CR with techniques which have
become available during last decade, is recommended as well as the
application of certain pre- and probiotics. It is concluded that
antibiotic inactivation may be an ancient strategy of nature which should
become incorporated in antibiotic treatment. Antibiotic use and
development of resistance may have occurred when ecosystems formed several
billions of years ago. Protection against antibiotics produced by
newcomers into the ecosystem may have developed as it was necessary to
maintain locally available nutrients for the inhabitants of the ecosystem.
Should this hypothesis be correct, it is plausible that antimicrobial
inactivation by antibiotic inactivating molecules is ubiquitous. In the
ecosystem of the digestive tract, molecules involved in inactivation may
predominantly be formed by microorganisms.
Can J Microbiol 2000 Oct;46(10):867-77
A review of antimicrobial resistance in Canada.
Blondeau JM, Vaughan D
Department of Clinical Microbiology, St. Paul's Hospital (Grey Nuns'),
Saskatoon, SK, Canada. firstname.lastname@example.org
Antimicrobial resistance is a global concern. Over the past 10 years,
considerable efforts and resources have been expended to detect, monitor,
and understand at the basic level the many different facets of emerging
and increasing resistance. This review summarizes our current
understanding of bacterial antimicrobial resistance issues in Canada with
particular emphasis given to the Enterobacteriaceae, Pseudomonas
aeruginosa, Staphylococcus aureus, Enterococcus, Neisseria meningitidis,
Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis,
and Streptococcus pyogenes. In addition, future concerns and programs for
ongoing surveillance are discussed.
Curr Opin Microbiol 2000 Oct;3(5):515-21
Pharmacodynamics in the study of drug resistance and establishing in vitro
susceptibility breakpoints: ready for prime time.
Dudley MN, Ambrose PG
Microcide Pharmaceuticals Inc., 850 Maude Ave., Mountain View, CA 94043,
Considerable advancements have been made in providing informative,
relevant interpretations of the results of antimicrobial susceptibility
tests to clinicians, clinical microbiologists, epidemiologists, and
researchers. At the same time, the science of pharmacokinetics has
flourished, and the importance of drug exposure in vivo on outcome is now
recognized by researchers and clinicians alike. More recently,
pharmacokinetic and quantitative measures of antimicrobial susceptibility
have been integrated using pharmacokinetic-pharmacodynamic (PK-PD) models
to forecast clinical and microbiological outcomes. Stochastic methods
utilizing patient population pharmacokinetics, target organism minimum
inhibitory concentration (MIC) distributions, and PK-PD targets from
non-clinical models of infection or clinical data have established a new
paradigm for determining in vitro susceptibility breakpoints and selection
of empirical therapy in clinical practice. Given the increasing problem of
antimicrobial resistance, these new tools are valuable additions for
clinicians, researchers, and regulatory authorities.
Curr Opin Microbiol 2000 Oct;3(5):496-501
Antimicrobial use and bacterial resistance.
Monroe S, Polk R
Medical College of Virginia, Richmond, Virginia 23298, USA.
The current epidemic of bacterial resistance is attributed, in part, to
the overuse of antibiotics. Recent studies have documented increases in
resistance with over-use of particular antibiotics and improvements in
susceptibility when antibiotic use is controlled. The most effective means
of improving use of antibiotics is unknown. Comprehensive management
programs directed by multi-disciplinary teams, computer-assisted
decision-making, and antibiotic cycling have been beneficial in
controlling antibiotic use, decreasing costs without impacting patient
outcomes, and possibly decreasing resistance.
South Med J 2000 Sep;93(9):842-8 [Texto
Confronting the problem of increasing antibiotic resistance.
Department of Internal Medicine, Mayo Clinic Jacksonville, Fla 32224, USA.
Significant increases in prevalence of resistance to antibiotics have been
observed in common pathogens of humans in the United States and worldwide.
The consequences of the appearance and spread of antibiotic resistance
have included increasing morbidity, mortality, and cost of health care.
The fundamental cause for the appearance and spread of antimicrobial
resistance has been increasing antimicrobial use. However, other factors
contribute in both inpatient and outpatient settings. Recognizing the
important causes of increasing antibiotic resistance in these settings has
led to practical recommendations, which health care facilities and
outpatient practitioners will need to review, adapt, and apply for maximum
local effectiveness for progress to be made in addressing one of the most
challenging problems facing modern medicine.
Am J Manag Care 2000 May;6(8 Suppl):S409-18
Emerging resistance problems among respiratory tract pathogens.
The number-1 indication for antibiotic prescriptions in the United States
is a respiratory tract infection. The changing spectrum of pathogens and
emerging bacterial resistance are changing the way these infections are
managed. The epidemiology of community-acquired pneumonia has changed
significantly in the past 20 years, with increased diversity of pathogens
and mortality. Emerging resistance in respiratory tract pathogens,
particularly to beta-lactams, is an increasing concern. Of the important
gram-negative pathogens, more than a third of Haemophilus influenzae
isolates are now resistant to beta-lactam antibiotics, as well as
virtually all isolates of Moraxella catarrhalis. Of the gram-positive
organisms, more than 40% of Streptococcus pneumoniae isolates are no
longer susceptible to penicillin, and methicillin resistance has been
reported in up to half of Staphylococcus aureus isolates in some
institutions. Among staphylococci, resistance to the beta-lactam
methicillin is often accompanied by resistance to multiple classes of
antibiotics, particularly the macrolides. Little resistance to
fluoroquinolones has been reported among gram-negative respiratory tract
pathogens and S pneumoniae, although increasing resistance may be seen as
these drugs are used with increasing frequency. In contrast,
fluoroquinolone resistance can develop rapidly in S aureus and appears to
be associated with methicillin resistance. Fortunately, many of the newer
fluoroquinolones appear to offer significant activity against
methicillin-resistant S aureus isolates and are active against
ciprofloxacin-resistant strains of S pneumoniae. Today, to combat
respiratory tract infections, a broad-based empiric therapy needs to be
used and bacterial resistance must be taken into account. New
antimicrobial options must be considered, with an emphasis on effective
drug use and optimal dosing. Even if a direct relationship between
antibiotic resistance and clinical outcomes in the treatment of pneumonia
in adults has not been extensively demonstrated, the increasing problem of
resistance has changed treatment approaches for respiratory tract
infections as a whole.
Rev Soc Bras Med Trop 2000 May-Jun;33(3):281-301
[Problems with gram-positive bacteria: resistance in staphylococci,
enterococci, and pneumococci to antimicrobial drugs].
[Article in Portugese]
Faculdade de Medicina de Teresopolis, Escola de Ciencias Medicas de Volta
Redonda, RJ, Brasil.
The resistance in staphylococci, enterococci, and pneumococci is reviewed.
The author also recalls the first cases, and presents an overview of the
distribution of cases in the world, the genetic and molecular mechanisms
of resistance, the importance in Brazil and therapeutic alternatives. The
factors that contribute to the dissemination of these problem bacteria and
the measures for their control are emphasized.
Infection 1999;27 Suppl 2:S32-4
Antimicrobial resistance--pharmacological solutions.
Infectious Diseases Unit, Chaim Sheba Medical Center, Tel-Hashomer,
The interaction between microbial resistance and antibacterial agents
occurs in a direct and an indirect fashion. Directly--through the
development of resistance to the agent used, or to agents of the same
class--as exemplified by the induction of beta-lactamase by both
gram-positive and gram-negative bacteria. It also takes place through the
development of resistance to compounds of different classes to the
compound used, as exemplified by the loss of Streptococcus pneumoniae
susceptibility to penicillin that is accompanied by a parallel loss of
sensitivity to erythromycin and to tetracycline. As for the indirect
way--microbial resistance may develop through selection of resistant
organisms when the patient is treated with antibiotics, when the
environment is contaminated with antibiotics (hospital) or when
antibacterial agents are used in agriculture and animal husbandry.
Infection 1999;27 Suppl 2:S24-8
Combination therapy as a tool to prevent emergence of bacterial
Dept. of Medical Microbiology, Canisius Wilhelmina Ziekenhuis Rotterdam,
Nijmegen, The Netherlands.
Emergence of resistance is an ever increasing problem. One of the methods
by which emergence of resistance may possibly be prevented, or at least
delayed, is the use of combination therapy. Since the emergence of
resistant mutants is a direct result of selective pressure by
antimicrobial therapy, the chance of mutants resistant to two
antimicrobials in the parent population being present is a product of
mutation frequencies, provided that resistance mechanisms are independent.
Comparative studies in in vitro pharmacokinetic models and in vivo
indicate that emergence of resistance is less common when combination
therapy is used. This is particularly true for microorganisms known to
develop resistance relatively quickly, such as Pseudomonas aeruginosa, and
resistance mechanisms which occur at a relatively high frequency.
Infection 1999;27 Suppl 2:S19-23
Drug resistance in intensive care units.
Albrich WC, Angstwurm M, Bader L, Gartner R
Medizinische Klinik, Klinikum Innenstadt der
Intensive care units (ICUs) are generally considered epicenters of
antibiotic resistance and the principal sources of outbreaks of
multi-resistant bacteria. The most important risk factors are obvious,
such as excessive consumption of antibiotics exerting selective pressure
on bacteria, the frequent use of invasive devices and relative density of
a susceptible patient population with severe underlying diseases.
Infections due to antibiotic-resistant bacteria have a major impact on
morbidity and health-care costs. Increased mortality is not uniformly
shown for all of these organisms: Methicillin-resistant Staphylococcus
aureus (MRSA) seems to cause significantly higher mortality, in contrast
to vancomycin-resistant enterococci (VRE). Therefore it is essential to
diminish these potential risk factors, especially by providing locally
adapted guidelines for the prudent use of antibiotic therapy. A quality
control of antimicrobial therapy within a hospital, and especially within
the ICU, might help to minimize the selection of multidrug-resistant
bacteria. The restricted use of antimicrobial agents in prophylaxis and
therapy has also been shown to have at least temporal effects on local
resistance patterns. New approaches to the problem of drug resistance in
ICUs are badly needed.
Infect Dis Clin North Am 2000 Jun;14(2):293-319
Pathogens resistant to antimicrobial agents. Epidemiology, molecular
mechanisms, and clinical management.
Kaye KS, Fraimow HS, Abrutyn E
Department of Internal Medicine, Harvard Medical School, Boston,
The emergence of resistance to antimicrobial agents continues to be a
major problem in the nosocomial setting and now in nursing homes and the
community as well. Bacteria use a variety of strategies to avoid the
inhibitory effects of antibiotic agents and have evolved highly efficient
means for the dissemination of resistance traits. Control of
antibiotic-resistant pathogens provides a major challenge for both the
medical community and society in general. To control the emergence of
resistant pathogens, CDC and infection control guidelines must be adhered
to, and antibiotics must be used more judiciously.
Clin Infect Dis 2000 May;30(5):799-808
Antimicrobial susceptibility testing: special needs for fastidious
organisms and difficult-to-detect resistance mechanisms.
Jorgensen JH, Ferraro MJ
Department of Pathology, The University of Texas Health Science Center,
San Antonio 78284-7750, USA. email@example.com
Clinical microbiology laboratories are faced with the challenge of
accurately detecting emerging antibiotic resistance among a number of
bacterial pathogens. In recent years, vancomycin resistance among
enterococci has become prevalent, as has penicillin resistance and
multidrug resistance in pneumococci. More recently, strains of
methicillin-resistant Staphylococcus aureus with reduced susceptibility to
vancomycin have been encountered. In addition, molecular techniques have
demonstrated that there are still problems detecting methicillin
resistance in staphylococci, especially in coagulase-negative species.
Among members of the family Enterobacteriaceae, mutated beta-lactamase
enzymes may confer difficult-to-detect resistance to later-generation
penicillins and cephalosporins. Anaerobic bacteria are no longer entirely
predictable in their susceptibility to agents that might be selected for
empiric therapy. Therefore, clinical microbiology laboratories may not be
able to rely on a single susceptibility testing method or system to detect
all those emerging resistant or fastidious organisms. For reliable
detection, laboratories may need to employ conventional, quantitative
susceptibility testing methods or use specially developed, single
concentration agar screening tests for some resistant species. Certain of
these screening tests are highly specific, while others may require
additional confirmatory testing for definitive results. Therefore,
laboratories must retain the versatility to apply several different
approaches to detect resistance in both common and infrequently
encountered bacterial pathogens.
Infect Dis Clin North Am 2000 Mar;14(1):67-81, viii
Bacterial resistance to antimicrobial agents in Latin America. The giant
Guzman-Blanco M, Casellas JM, Sader HS
Infectious Disease and Microbiology Unit, Hospital Vargas de Caracas,
Resistant bacteria are emerging in Latin America as a real threat to the
favorable outcome of infections in community- and hospital-acquired
infections. Despite present extensive surveillance, healthcare workers who
most need the information may be unaware of this growing problem.
Outbreaks of meningococci with diminished susceptibility to penicillin
have been reported in the region; a constant increase of resistance to
penicillin in pneumococci and poor activity of commonly used oral
antibiotics for the treatment of community-acquired urinary tract
infections have made the treatment of these infections more difficult.
Reports from tertiary hospitals are similar to many other areas of the
world, with increasing frequency of Klebsiella pneumoniae-carrying
extended-spectrum beta-lactamase, multiresistant strains of Pseudomonas
aeruginosa and Acinetobacter baumanni in ICU settings, and reports of
methicillin-resistant Staphylococcus aureus and vancomycin-resistant
enterococci. A surveillance network readily accessible to those who
prescribe antibiotics in Latin America is highly desirable.
J Chemother 1999 Dec;11(6):518-23
Emerging antimicrobial resistance in the surgical compromised host.
Department of Clinical Microbiology, University College Hospital, London,
Improvements in the treatment of compromised patients have resulted in
their prolonged survival in a debilitated state. Patients have repeated
courses of antibiotics and become colonised with multiresistant pathogens
during a stay in the intensive care unit. Surgical wound infections can
then be very difficult to treat. Methicillin-resistant Staphylococcus
aureus is now common although wide variations in prevalence exist between
countries and regions. Klebsiella spp with multiple resistance is a common
cause of septicemia and can be associated with cephalosporin use.
Acinetobacter spp and vancomycin-resistant enterococci can cause
infections resistant to all readily available antibiotics. The prevalence
of infection with each of these pathogens is increasing. Control measures
should include hand washing, universal precautions for infection control,
source isolation, restrictive antibiotic policy and antibiotic rotation.
Although new agents currently in trials may be effective in the long term,
the future for antibiotic treatment or prophylaxis of surgical infections
is in doubt.
J Postgrad Med 1995 Apr-Jun;41(2):29-30
Antimicrobial resistance--a strident alarm.
Mayo Clin Proc 2000 Feb;75(2):200-14
Clinical aspects of antimicrobial resistance.
Virk A, Steckelberg JM
Division of Infectious Diseases and Internal Medicine, Mayo Clinic
Rochester, Rochester, Minnesota, USA.
Soon after penicillin was introduced into clinical use, an enzyme
(penicillinase) that inactivated it was discovered. Since then, the
variety of antimicrobial agents has increased substantially, along with a
parallel increase in resistant pathogenic microorganisms. Resistance is
now recognized against all available antimicrobial agents. Factors
influencing the emergence of resistance include indiscriminate use of
antibiotics, prolonged hospitalizations, increasing numbers of
immunocompromised patients, and medical progress resulting in increased
use of invasive procedures and devices. This article provides an update on
clinical aspects of a few commonly found resistant microorganisms relevant
to day-to-day clinical practice. A discussion of all resistant organisms
is beyond the scope of this report. Both viral and mycobacterial
resistance have been addressed in previous articles in this symposium.
Emerging Infectious Diseases 1999;Vol5 Nro3 [Texto
Bacterial Resistance to Antimicrobial Agents: Selected Problems in France,
1996 to 1998 Helene Aubry-Damon* and Patrice Courvalin?
*Institut de Veille Sanitaire, Saint-Maurice, France; and ?Centre National
de Référence des Antibiotiques, Institut Pasteur, Paris, France
Drugs 1999 Oct;58(4):589-607
Antibiotic usage in animals: impact on bacterial resistance and public
van den Bogaard AE, Stobberingh EE
Department of Medical Microbiology, University Maastricht, The
Antibiotic use whether for therapy or prevention of bacterial diseases, or
as performance enhancers will result in antibiotic resistant
micro-organisms, not only among pathogens but also among bacteria of the
endogenous microflora of animals. The extent to which antibiotic use in
animals will contribute to the antibiotic resistance in humans is still
under much debate. In addition to the veterinary use of antibiotics, the
use of these agents as antimicrobial growth promoters (AGP) greatly
influences the prevalence of resistance in animal bacteria and a poses
risk factor for the emergence of antibiotic resistance in human pathogens.
Antibiotic resistant bacteria such as Escherichia coli, Salmonella spp.,
Campylobacter spp. and enterococci from animals can colonise or infect the
human population via contact (occupational exposure) or via the food
chain. Moreover, resistance genes can be transferred from bacteria of
animals to human pathogens in the intestinal flora of humans. In humans,
the control of resistance is based on hygienic measures: prevention of
cross contamination and a decrease in the usage of antibiotics. In food
animals housed closely together, hygienic measures, such as prevention of
oral-faecal contact, are not feasible. Therefore, diminishing the need for
antibiotics is the only possible way of controlling resistance in large
groups of animals. This can be achieved by improvement of animal husbandry
systems, feed composition and eradication of or vaccination against
infectious diseases. Moreover, abolishing the use of antibiotics as feed
additives for growth promotion in animals bred as a food source for humans
would decrease the use of antibiotics in animals on a worldwide scale by
nearly 50%. This would not only diminish the public health risk of
dissemination of resistant bacteria or resistant genes from animals to
humans, but would also be of major importance in maintaining the efficacy
of antibiotics in veterinary medicine.
BMJ 1998 Sep 5;317(7159):657-60 [Texto
The origins and molecular basis of antibiotic resistance.
Department of Microbiology, and Antimicrobial Research Centre, University
of Leeds, Leeds LS2 9JT. P.M.Hawkey@Leeds.ac.uk
BMJ 1998 Sep 5;317(7159):652-4 [Texto
The epidemiology of antimicrobial resistance in hospital acquired
infections: problems and possible solutions.
Department of Clinical Microbiology, Hopital Erasme, Universite Libre de
Bruxelles, 808 route de Lennik, 1070 Brussels, Belgium.
BMJ 1998 Sep 5;317(7159):651 [Texto
Surveillance of antimicrobial resistance--an international perspective.
Williams RJ, Ryan MJ
Division of Emerging and other Communicable Diseases Surveillance and
Control, World Health Organisation, CH-1211 Geneva, Switzerland.
BMJ 1998 Sep 5;317(7159):647-50 [Texto
Antimicrobial resistance in developing countries.
Hart CA, Kariuki S
Department Medical Microbiology and Genitourinary Medicine, University of
Liverpool, Liverpool L69 3GA. firstname.lastname@example.org
N Engl J Med 1996 Nov 7;335(19):1445-53
Gold HS, Moellering RC
Division of Infectious Diseases, Deaconess Hospital and Harvard Medical
Boston, MA 02215, USA.