Antibiotic utilization strategies to limit antimicrobial resistance

Antimicrobial resistance is now being recognized as a major factor determining morbidity, mortality, and cost in the intensive care unit (ICU). Various strategies to limit its spread have evolved with our understanding and are based on four basic principles: infection prevention, infection eradication, containment of resistant species, and optimization of antibiotic utilization. The optimization of antibiotic utilization, at its most basic level, is the appropriate use of antibiotics and the limitation of unnecessary antibiotic administration/exposure consisting of appropriate diagnosis, acquiring appropriate culture and sensitivity data, implementing the most appropriate treatment, selecting appropriate antibiotics, and dosing appropriately. In addition various antibiotic utilization strategies including antibiotic utilization guidelines, formulary restriction, and antibiotic cycling or rotation have evolved from our understanding of the impact of changes in antibiotic utilization on subsequent antibiotic susceptibility patterns. These strategies can be utilized as a part of a multidisciplinary approach to limit the appearance and dissemination of antimicrobial resistance in our ICUs.     

Extended-spectrum beta-lactamases

Extended-spectrum beta-lactamases, most commonly found in Klebsiella pneumoniae and Escherichia coli, have increased markedly in the past decade, particularly in the intensive care unit setting. The problem has been significant in the United States but is even more prevalent in parts of Latin America and Asia. These plasmid-mediated beta-lactamases confer resistance to broad-spectrum beta-lactam antibiotics, including third- and fourth-generation cephalosporins, aztreonam, and extended-spectrum penicillins. Other resistances, such as aminoglycoside resistance and trimethoprim/sulfamethoxazole resistance, are often cotransferred on the same plasmid. Fluoroquinolone resistance is often associated, resulting in an organism that is resistant to most of the usual antimicrobial options. Although carbapenems are currently considered the drugs of choice for these pathogens, widespread use of these agents may lead to other resistance problems. Due to limited therapeutic options, prevention and control measures are important. Traditional infection control measures, such as contact precautions, are recommended to prevent spread in intensive care units. In addition, because this type of antimicrobial resistance appears to be particularly influenced by antibiotic utilization, antibiotic control measures may also be a very important intervention in limiting the spread of extended-spectrum beta-lactamases.     

Responsibility of the infectious disease community for optimal use of antibiotics: views of the membership of the Infectious Diseases Society of America

A questionnaire was sent to 1,500 members and fellows of the Infectious Diseases Society of American to elicit their views on the use of antimicrobial agents. The rate of return was 58.7%. A high proportion of respondents (86.8%) stated that they had a strong professional interest in antimicrobial therapy and were active in infection control and antibiotic use in their institutions--488 hospitals including community, university, children's, and governmental facilities. The membership was concerned with problems of antibiotic use in hospitals, laboratory methods of reporting susceptibility, promotional practices of industry, and development of microbial resistance. Members were troubled by how best to deal with excessive use of antibiotics in hospitals. Respondents strongly supported efforts to improve the control of antimicrobial use in hospitals and to examine issues of drug use and resistance in developing countries; they provided suggestions for development of a code of ethical conduct with industry.     

Antibiotic resistance in the intensive care unit

Antimicrobial resistance has emerged as an important determinant of outcome for patients in the intensive care unit (ICU). This is largely due to the administration of inadequate antimicrobial treatment, which is most often related to bacterial antibiotic resistance. In addition, the escalating problem of antimicrobial resistance has substantially increased overall health care costs. This increase is a result of prolonged hospitalizations and convalescence associated with antibiotic treatment failures, the need to develop new antimicrobial agents, and the implementation of broader infection control and public health interventions aimed at curbing the spread of antibiotic-resistant pathogens. Intensive care units are unique because they house seriously ill patients in confined environments where antibiotic use is extremely common. They have been focal points for the emergence and spread of antibiotic-resistant pathogens. Effective strategies for the prevention of antimicrobial resistance in ICUs have focused on limiting the unnecessary use of antibiotics and increasing compliance with infection control practices. Clinicians caring for critically ill patients should consider antimicrobial resistance as part of their routine treatment plans. Careful, focused attention to this problem at the local ICU level, using a multidisciplinary approach, will have the greatest likelihood of limiting the development and dissemination of antibiotic-resistant infections.     

Pharmacokinetics of antibiotics in the lungs

This paper reviews current knowledge on the relationship between local penetration or antibiotics and therapeutic efficacy in pulmonary and bronchial infections. The antimicrobial drug concentration at the site of infection is supposedly determinative for the efficacy of the antibiotic treatment but the number of studies in respiratory infections supporting this hypothesis is limited. The mechanisms responsible for the pulmonary deposition or orally or systemically administered antibiotics include passive diffusion, active transport, bulk flow and permeation. The penetration of antimicrobial drugs into the respiratory tract is influenced by both host-related factors, such as inflammation or mechanical injury, and drug-related factors, such as molecular weight. In addition, local bio-inactivation can occur. The final bioactive antibiotic concentration at the site of the respiratory infection is, therefore, the result or a very complex dynamic process. Different sampling and measuring methods have been used for the assessment of antibiotic concentrations at the site of respiratory infections. Concentrations in sputum, bronchial secretions and biopsy specimens have been correlated with serum concentrations and clinical outcome. Bronchoalveolar lavage could be a promising technique for evaluating antibiotic drug concentrations in alveolar lining fluid. For many antibiotics, data concerning penetration and pharmacokinetic behaviour in the respiratory tract are lacking.     

Role of the infectious disease specialist in containing costs of antibiotics in the hospital

Antimicrobial agents account for a significant proportion of drug expenditures and are used inappropriately approximately half the time in hospital practice. This has led to substantial increases in medical costs for hospitalized patients. Methods have been proposed to reduce inappropriate use of antibiotics, particularly in hospitalized patients. Two of these methods, education and control, were employed effectively by infectious disease specialists at a university teaching hospital to reduce inappropriate use of second-generation cephalosporins. These efforts resulted in significant savings of approximately $130,00 per year. The infectious disease specialist may also make major contributions to cost containment of antibiotics in other equally important areas, including other classes of antibiotics, inappropriate daily frequency, excessive duration of administration, and prevention of adverse drug reactions. The infectious disease specialist is better trained in appropriate antimicrobial use and clinically more knowledgeable in treating infections than other medical specialists and is the best-equipped member of the medical staff to educate the medical community on antibiotic use and to control antibiotic costs.     

Extended-spectrum beta-lactamases

Resistance to broad-spectrum cephalosporins among Klebsiella pneumoniae has increased significantly, particularly in the intensive care unit setting, in the past decade.The problem has been noted not only in the United States, but around the world. A major mechanism responsible for this is the emergence of extended-spectrum beta-lactamases (ESBLs).These plasmid-mediated beta-lactamases confer resistance to broad-spectrum beta-lactam antibiotics, including third- and fourth-generation cephalosporins, aztreonam, and extended-spectrum penicillins. Other resistances, such as aminoglycoside and trimethoprim-sulfamethoxazole resistance, are often cotransferred on the same plasmid. Fluoroquinolone resistance is also frequently associated, resulting in an organism resistant to most broad-spectrum options. The carbapenems are currently considered the drug of choice for these pathogens. Prevention and control measures are important because of the multiresistant nature of these pathogens. Such traditional infection control measures as contact precautions are recommended. In addition, because this type of antimicrobial resistance appears to be particularly influenced by antibiotic use, antibiotic control measures may also be a very important intervention in controlling the spread of ESBLs.     

Política de antibióticos. Comisión de Infecciones y uso de antimicrobianos

The antibiotic policy is the set of strategies and activities undertaken to organize the antimicrobial treatment in the hospital, and achieve health outcomes for patients. The basic principles are to be direct evidence-based medicine, local epidemiology and freedom for prescribing physicians. An antibiotic policy is now more necessary than ever for clinical, epidemiological and economic reasons. The Infection Committee is responsible for the antibiotics policy in hospitals. Its functions as an advisory body to the medical directorate are the analysis of the epidemiology of the infections in the center, measures for its prevention and control, improving the appropriate use of antimicrobials, training, and knowledge production. To achieve clinical, environmental and economic policy objectives of antibiotics is not easy. The agreement of hundreds of professionals for recommendations on indications, dosage and duration of antibiotic treatment, based on the best scientific evidence and local guides is complex, but it can be done. The key to this is that the Infection Committee develops antimicrobial stewardship through a multidisciplinary team and professional leadership, and has the institutional support to ensure that the proper use of antimicrobials is a priority for the center, and therefore of each of the services involved, and that the team has the resources for antimicrobial stewardship.     

Effectiveness of programs to decrease antimicrobial resistance in the intensive care unit

Resistance of microbes to antibiotics is an increasing problem in intensive care units (ICUs) with a prevalence of 86% in some isolates. Resistance results in increased morbidity, mortality, and increased costs. Risk factors associated with the development of resistance and strategies to combat resistance are discussed. Risk factors include increased antibiotic use, host factors including severity of illness and length of stay, and lack of adherence to infection control practices. Multiple strategies to decrease resistance have been studied. Changing antimicrobial practices via guideline development, antibiotic restriction, use of information systems technology, crop rotation, narrowing spectrum of empiric antibiotics, multidisciplinary approaches, and selective decontamination have had variable results. Prevention of horizontal transmission via handwashing, glove and gown use, alternatives to soap, and improving the workload and facilities for health care workers is discussed. Primary prevention via decreased length of stay, selective digestive decontamination, vaccine development, and decreased use of invasive devices also plays a role.     

Infections due to Acinetobacter baumannii in the ICU

Acinetobacter species are widespread environmental, nonfermentative, aerobic, gram-negative coccobacilli. Most infections due to this organism are opportunistic in nature and occur in patients who spend extended time in the intensive care unit (ICU) due to severe underlying disease, and who need prolonged therapy with mechanical ventilation and antimicrobial agents. Because the only factor amenable to prevention in this setting is antimicrobial therapy, avoidance of unnecessary antibiotics should be a high priority in management of such patients. Nosocomial spread of A. baumannii in the ICU setting has often been attributed to ventilatory equipment and to colonized nursing and respiratory personnel via hand transmission. In fact, the epidemiology of nosocomial respiratory colonization and/or infection with A. baumannii is now commonly much more complex due to the coexistence of epidemic cases with unrelated sporadic cases caused by different strains. This underscores the necessity to use molecular typing to improve the detection of microepidemics amenable to early control. Crude mortality rates of 30 to 75% have been reported for nosocomial infection due to Acinetobacter species, with the highest rates reported in ventilator-dependent patients. As with many other opportunistic gram-negative bacilli, increasing antibiotic resistance has hindered the therapeutic management of nosocomial infection due to Acinetobacter species. A. baumannii are now frequently resistant to most available antibacterial drugs, with some centers reporting up to 80% of strains resistant to all aminoglycosides. Even resistance to imipenem, which was for several years the most effective drug in treating Acinetobacter nosocomial infections, has now been described in several reports. Unfortunately, the unique propensity of Acinetobacter species to develop resistance to multiple antimicrobial agents reinforces concerns about the imminence of a post-antimicrobial era where no effective antibiotics will be available to treat this type of infection.     

重症监护室耐药非发酵革兰阴性菌院内感染的危险因素及治疗进展研究

多耐药非发酵革兰阴性菌已成为重症监护室院内感染的重要病原菌,近年来其检出率在全球有逐年上升的趋势,对其危险因素和治疗进展的探讨具有重要意义.入院前有抗生素使用史、反复插管、最初不恰当抗生素治疗即病原菌对所用抗菌药物不敏感、重症监护室住院时间延长等是耐药菌院内感染常见的危险因素.关于耐药菌院内感染的治疗,采用早期适当联合用药原则,控制感染.     

Impact of antibiotic-resistant bacteria on the outcome of ventilator-associated pneumonia

Since antibiotic resistance has become a worldwide concern, there has been an ongoing debate as to whether infections caused by resistant bacteria are associated with higher mortality. Because resistant strains do not appear to be more virulent, differences in outcome may principally relate to patients' characteristics before or at the time of infection onset, and to high rates of inappropriate empirical antimicrobial treatment prescribed for antibiotic-resistant infections. In two large series of severe Staphylococcus aureus and Pseudomonas aeruginosa ventilator-associated pneumonia, we recently demonstrated that antibiotic resistance does not significantly affect intensive care unit mortality of patients receiving appropriate initial antibiotics. However, antibiotic resistance was consistently found to increase hospital length of stay. Early identification of patients with risk factors favoring antibiotic-resistant infections should prompt the initiation of an empirical antibiotic regimen covering these highly resistant bacteria, which can usually be deescalated 48 to 72 hours later when the results of microbiological samples culture become available.     

Patterns of antimicrobial use for respiratory tract infections in older residents of long-term care facilities

OBJECTIVES: To describe patterns of antimicrobial use for respiratory tract infections (RTIs) in older residents of long‐term care facilities (LTCFs). DESIGN: Data from a prospective, randomized, controlled study of the effect of vitamin E supplementation on RTIs conducted from April 1998 through August 2001 were analyzed. SETTING: Thirty‐three LTCFs in the greater Boston area. PARTICIPANTS: Six hundred seventeen subjects aged 65 and older residing in LTCFs. MEASUREMENTS: RTIs, categorized as acute bronchitis, pneumonia, common cold, influenza‐like illness, pharyngitis, and sinusitis, were studied for appropriateness of antimicrobial use, type of antibiotics used, and factors associated with their use. For cases in which drug treatment was administered, antibiotic use was rated as appropriate (when an effective drug was used), inappropriate (when a more‐effective drug was indicated), or unjustified (when use of any antimicrobial was not indicated). RESULTS: Of 752 documented episodes of RTI, overall treatment was appropriate in 79% of episodes, inappropriate in 2%, and unjustified in 19%. For acute bronchitis, treatment was appropriate in 35% and unjustified in 65% of cases. For pneumonia, treatment was appropriate in 87% of episodes. Of the most commonly used antimicrobials, macrolide use was unjustified in 43% of cases. No statistically significant differences in the patterns of antibiotic use were observed when stratified according to age, sex, race, or comorbid conditions, including diabetes mellitus, dementia, and chronic kidney disease. CONCLUSION: Antimicrobials were unjustifiably used for one‐fifth of RTIs and more than two‐thirds of cases of acute bronchitis, suggesting a need for programs to improve antibiotic prescribing at LTCFs.     

Bacterial resistance and topical antimicrobial wash products.

Current scientific evidence has not shown that a link exists between the use of topical antimicrobial formulations and antiseptic or antibiotic resistance. As a result of the extensive history and varied use of antiseptic products and ingredients, any selective pressure for antibiotic resistance that may be occurring or may be uncovered in the future because of antiseptic use would be expected to be insignificant compared with the selective pressure because of antibiotic use. This review illustrates the effectiveness of topical antimicrobial wash products against antibiotic-resistant and antiseptic-resistant bacteria in use settings as well as the studies performed (antiseptic, deodorant, and oral care) demonstrating the lack of development of resistance in long-term clinical studies. Although these studies illustrate that the use of topical antimicrobial products have not been shown to play a role in the fluctuations of the specific composition or resistance of the skin flora, changes in skin flora have been shown to occur. Based on current knowledge, the benefit from use of topical antimicrobial wash products in combination with standard infection control and personal hygiene practices far outweighs the risk of increased antibiotic resistance.