Off-label abuse of antibiotics by bacteria

Antibiotics and antibiotic resistance made news on several fronts in the past year. Many public health organizations, including the CDC, used terms such as “crisis”, “catastrophic consequences”, and “nightmare scenario” to highlight the rapid emergence and spread of antibiotic resistance. A report from the Pew Commission on Industrial Farm Animal Production, on the fifth anniversary of the publication of its landmark 2008 report, noted that state and federal legislative efforts to limit non-therapeutic use of antibiotics in animal production were thwarted by drug and food animal industries. In its lobbying disclosures, the Farm Bureau stated that such efforts to limit use of animal antibiotics were “based on emotion and no credible peer reviewed science.” Meanwhile, there have been inexorable advances in our understanding of the molecular mechanisms by which antibiotics induce diversity and resistance in bacteria. This article reviews one study that probed the role of the bacterial general stress response in sub-inhibitory antibiotic-induced mutagenesis and antibiotic resistance.     

Expanding the role of the infection control professional in the cost-effective use of antibiotics

There is a growing demand that health care expenses be contained and that excessive and inappropriate use of antibiotics be eliminated. At the University of California, San Diego Medical Center, strategies aimed at controlling drug usage and subsequently reducing costs have been implemented and found to be effective. Mechanisms designed to achieve such goals without diminishing quality of care involve expanding the role of the infection control professional (ICP) while implementing antibiotic control stratagems such as antimicrobial utilization teams, antibiotic order sheets, audits of use, automatic stop orders, computer-assisted management, drug use reviews, educational efforts, formulary practice, restricted drug policies, and target drug monitoring. The infection control professional, as well as other members of the antimicrobial utilization team, contributes to the promotion of the appropriate use of antibiotics in part by identifying individual cases in which antibiotics might be used inappropriately, such as for the treatment of colonization rather than infection or when appropriate microbiologic testing has not been carried out.     

Understanding the Mechanisms That Drive Phage Resistance in Staphylococci to Prevent Phage Therapy Failure

Despite occurring at the microscopic scale, the armed race between phages and their bacterial hosts involves multiple mechanisms, some of which are just starting to be understood. On the one hand, bacteria have evolved strategies that can stop the viral infection at different stages (adsorption, DNA injection and replication, biosynthesis and assembly of the viral progeny and/or release of the newly formed virions); on the other, phages have gradually evolved counterattack strategies that allow them to continue infecting their prey. This co-evolutionary process has played a major role in the development of microbial populations in both natural and man-made environments. Notably, understanding the parameters of this microscopic war will be paramount to fully benefit from the application of phage therapy against dangerous, antibiotic-resistant human pathogens. This review gathers the current knowledge regarding the mechanisms of phage resistance in the Staphylococcus genus, which includes Staphylococcus aureus, one of the most concerning microorganisms in terms of antibiotic resistance acquisition. Some of these strategies involve permanent changes to the bacterial cell via mutations, while others are transient, adaptive changes whose expression depends on certain environmental cues or the growth phase. Finally, we discuss the most plausible strategies to limit the impact of phage resistance on therapy, with a special emphasis on the importance of a rational design of phage cocktails in order to thwart therapeutic failure.     

Pathogens resistant to antimicrobial agents. Epidemiology, molecular mechanisms, and clinical management

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.     

Evidence for antibiotic cycling in control of resistance

There is growing concern about the increasing rates of resistance among human pathogens. These high rates of resistance, which are a consequence of antibiotic misuse, highlight the need for a thorough revision of strategies that deal with the proper use of antibiotics. The so-called 'optimal use of all antibiotics', restriction guidelines and use of a combination of antibiotics are well established strategies in most hospitals but new potential strategies, such as dosage optimization and antibiotic cycling, require further study and evaluation. Cycling antibiotic therapy consists of the scheduled replacement of one antibiotic for another, in order to avoid the development of bacterial resistance. Initial studies suggest that this strategy could be useful in reducing the rates of bacterial resistance as well as the incidence of nosocomial infections caused by Gram-negative bacilli in intensive care unit patients. This strategy, however, does not prevent antibiotic misuse and needs to be applied in a complete antibiotic policy program.     

Acinetobacter

Members of the genus Acinetobacter are oxidase negative, aerobic Gram-negative coccobacilli, which have evolved taxonomically from former strains of the Mima-Herrelia group. Their natural habitat is human skin and mucous membranes, water, soil, vegetation, and sewage. The most common multiresistant nosocomial pathogen among 19 genospecies is the A. calcoaceticus-baumannii complex ( A. baumannii). This species is not a common component of normal human acinetobacter colonization, and its ecological origin remains unknown. Outbreaks of nosocomial acinetobacter infection are due to spread of one or a few clones among patients, personnel, and the inanimate hospital environment. Thus, strict implementation of infection control procedures is the major technique for prevention and suppression of such outbreaks. Surveillance cultures of personnel and the environment; molecular genotyping of isolates; cohorting of colonized or infected patients and staff; and topical application of polymyxin B to colonized wounds have been used to enhance standard infection control procedures. Antimicrobial resistance to beta lactam antibiotics in Acinetobacter is due primarily to a combination of chromosomal beta lactamase production and reduced outer membrane permeability. Carbapenem resistance is an increasing phenomenon and restriction of late-generation cephalosporin and carbapenem utilization should be considered in outbreak control. Effective therapy of multiresistant Acinetobacter infection may require a variety of potentially synergistic antibiotic combinations.     

Faut-il proposer une adaptation posologique lors d’une antibiothérapie ?

While we are confronted with the major increase in antibiotic resistance, the preservation of existing antibiotics has become an absolute necessity both to achieve therapeutic success and to limit the risks of the emergence of resistance. The optimization of antibiotic use and dosages must have a threefold objective: guarantee antibacterial efficacy, limit toxicities and limit emergence of resistant strains. However, with the increase in the number of multipathological patients, particularly those with renal or hepatic impairment, the increase in the number of patients with extreme weights and the use of antibiotics with narrower therapeutic margins, the adaptation of antibiotic dosages is becoming increasingly important. By reminding some principles of pharmacokinetics and pharmacodynamics of antibiotics (PK/PD), the necessary objectives for clinical effectiveness of most antibiotic classes are reviewed and several examples of situations where dosage adjustments are necessary will be given. In particular, adjustment of antibiotic dosages in obese patients will be discussed. Adaptation is not limited to the adaptation of the total daily dose. The PK/PD parameters also tell us that the mode of administration (intermittent versus continuous, number of injections per day, etc.) is also an essential point to consider. By taking examples concerning some molecules, infections and difficult clinical situations, we review situations in which dosage adjustments appear necessary.     

Newer antibiotics for the treatment of respiratory tract infections

PURPOSE OF REVIEW: In this review, we highlight some of the developments achieved over the past 2 years in the field of novel antimicrobial compounds. RECENT FINDINGS: Modification of existing compound classes to create more powerful compounds capable of overcoming pathogen resistance and the introduction of completely new classes of antibiotics and inhibitors of new bacterial targets or inhibitors of genes relating to virulence or pathogenesis are the strategies more commonly employed in pharmacologic research. Ketolides, oxazolidinones, streptogramins, glycylcyclines, and peptide deformylase inhibitors are among the most promising classes of antibiotics. Recently, several lines of research have documented that it is effective to target the infection process rather than killing bacteria. This is important because it is likely that such a therapeutic strategy could ablate infection without inducing resistance. SUMMARY: Emergence of resistance to the antibiotics currently employed in clinical practice is a continual stimulus for further research aimed at identifying novel antimicrobial compounds. These drugs will perhaps effectively fight against bacteria that now are scarcely controlled by the traditional antimicrobial agents. Health care personnel must appreciate that only judicious use of antimicrobial drugs will prevent the further uncontrolled spread of bacterial resistance. Implementation of reference guidelines would probably be an effective way to limit antibiotic misuse.     

多重耐药铜绿假单胞菌耐药状况分析

目的 了解医院铜绿假单胞菌对常用抗菌药物的耐药谱动态变化,为临床合理选用抗菌药物提供依据.方法 应用回顾性调查方法,对本院从2005年1月至2009年6月间临床样本分离的铜绿假单胞菌的药敏试验进行对比统计分析.结果 所分离出的1125株铜绿假单胞菌对常用抗菌药物的耐药率总体呈上升趋势.耐药率最低的是美罗培南（33%）.铜绿假单胞菌对常见抗菌药物的耐药性均有显著性变化.结论 本地区铜绿假单胞菌耐药率有显著性变化,多重耐药现象严重,动态监测其耐药谱变化是防止铜绿假单胞菌的感染率攀升的重要措施.     

Second and third line treatment options for Helicobacter pylori eradication

Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and thirdline treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.     

Current concepts of therapy for otitis media

The therapy for acute otitis media is currently a topic in evolution. What was once a straightforward approach of matching middle ear pathogens to appropriate antibiotics has become a complex calculus that attempts to balance multiple terms such as spontaneous cure, emergence of resistance, pharmacokinetics-dynamics, antibiotic therapeutic efficacy, suppurative complications, and cost. This review highlights new developments in our understanding of this complex interaction of the issues surrounding a physician’s decision to begin antibiotic therapy for acute otitis media.     

Appropriate use of antibiotics for respiratory infections: review of recent statements and position papers

Respiratory infections are among the most common reasons for prescribing antibiotics. The excessive use of antibiotics in ambulatory practice has contributed to the emergence and spread of antibiotic resistance. The appropriate use of antimicrobial agents for respiratory infections could potentially reduce the emergence of antibiotic resistance. This article reviews recent guidelines and position papers on the appropriate antibiotic treatment for respiratory infections. There is a wide consensus that antibiotics are not appropriate for the treatment of most cases of acute bronchitis, pharyngitis, and rhinosinusitis. The recently published community-acquired pneumonia guidelines emphasized the importance of selecting antibiotic regimens active against both typical and atypical pathogens. However, there is disagreement regarding the routine use of the new quinolones.     

Evaluating treatment protocols to prevent antibiotic resistance

The spread of bacteria resistant to antimicrobial agents calls for population-wide treatment strategies to delay or reverse the trend toward antibiotic resistance. Here we propose new criteria for the evaluation of the population-wide effects of treatment protocols for directly transmitted bacterial infections and discuss different usage patterns for single and multiple antibiotic therapy. A mathematical model suggests that the long-term benefit of single drug treatment from introduction of the antibiotic until a high frequency of resistance precludes its use is almost independent of the pattern of antibiotic use. When more than one antibiotic is employed, sequential use of different antibiotics in the population (“cycling”) is always inferior to treatment strategies where, at any given time, equal fractions of the population receive different antibiotics. However, treatment of all patients with a combination of antibiotics is in most cases the optimal treatment strategy.     

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.     

Serratia bacteremia: review of 118 cases

A review was conducted of 118 episodes of serratia bacteremia in cancer patients during a 16-year period. The infection occurred most commonly in patients with acute leukemia. Most patients acquired the infection in the hospital, and 61% had received antibiotic therapy during the preceding 10 days. Fever occurred in 90% of cases and shock in 18%. Thirty-eight percent of patients had concomitant pneumonia. Patients with shock, pneumonia, or hemorrhage had a substantially poorer prognosis. The response rate was 75% for patients who received appropriate antibiotics, 22% for those who received inappropriate antibiotics, and 29% for those who received no antibiotics. Patients who continued to have positive blood culture results while receiving appropriate antibiotic therapy had a poor diagnosis. Patients who received only an aminoglycoside had the poorest response rate among those who received appropriate therapy.