The emergence of bacterial resistance and its influence on empiric therapy. - Related Documents




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485701.0000The emergence of bacterial resistance and its influence on empiric therapy. The discovery of antimicrobial agents had a major impact on the rate of survival from infections. However, the changing patterns of antimicrobial resistance caused a demand for new antibacterial agents. Within a few years of the introduction of penicillin, the majority of staphylococci were resistant to that drug. In the 1960s the production of the semisynthetic penicillins provided an answer to the problem of staphylococcal resistance. In the early 1960s most Escherichia coli were susceptible to the new beta-lactam antibiotic ampicillin; by the end of that decade, plasmid-mediated beta-lactamase resistance was found in 30%-50% of hospital-acquired E. coli. Use of certain agents resulted in the selection of bacteria, such as Klebsiella, that are intrinsically resistant to ampicillin. The original cephalosporins were stable to beta-lactamase, but the use of these agents was in part responsible for the appearance of infections due to Enterobacter species, Citrobacter species, and Pseudomonas aeruginosa. These bacteria, as well as Serratia, were resistant to many of the available beta-lactam agents. Aminoglycosides initially provided excellent activity against most of the facultative gram-negative bacteria. However, the widespread dissemination of the genes that cause production of the aminoglycoside-inactivating enzymes altered the use of those agents. Clearly, the evolution of bacterial resistance has altered the prescribing patterns for antimicrobial agents. Knowledge that beta-lactam resistance to ampicillin or cephalothin is prevalent is causing physicians to select as empiric therapy either a combination of two or more agents or agents to which resistance is uncommon. The new cephalosporins offer a broad spectrum of anti-bacterial activity coupled with low toxicity. However, physicians must closely follow the changing ecology of bacteria when these agents are used, because cephalosporins can also select bacteria resistant to themselves and thereby abolish their value as empiric therapy.19836342103
475410.9999Enterococci and streptococci. Besides Staphylococcus aureus, other Gram-positive bacteria have become multidrug-resistant and cause therapeutic problems, particularly amongst hospitalised patients. The acquisition of vancomycin resistance by strains of Enterococcus faecium and Enterococcus faecalis is of particular concern and has resulted in treatment failures. Some of the infections caused by these bacteria do respond to treatment with new antibiotics that have been released in the last few years, however more options are required as not all enterococci are inherently susceptible and resistance is beginning to emerge amongst those that were susceptible. Resistance to commonly used antibiotics is also emerging in Streptococcus spp., particularly to the tetracyclines and macrolides. In both genera, multiresistant strains spread between patients and between hospitals. In the laboratory, these bacteria show considerable susceptibility to tigecycline, with little propensity to develop resistance, indicating that tigecycline could assume an important role in controlling infections caused by these Gram-positive bacteria.200717659211
485820.9999Successful interventions for gram-negative resistance to extended-spectrum beta-lactam antiobiotics. Antibiotic resistance among nosocomial pathogens in this country's hospitals adds significantly to patient morbidity and mortality, and the cost of health care. Optimism for identifying antimicrobial agents that would "solve the problem" of resistance has been replaced by a much more guarded and realistic view of the battle between humans and pathogenic microorganisms. Efforts now are more appropriately directed toward limiting, rather than completely eliminating, resistance, generally by either infection control or antibiotic control measures, and sometime combinations of the two. Methicillin-oxacillin resistance in Staphylococcus aureus (MRSA) results from the expression of an acquired penicillin-binding protein (PBP 2a) that is not transferable in vitro. In most hospitals, even those with high percentages of MRSA, relatively few resistant clones are identified, suggesting transmission of individual strains throughout the hospital population. Because person-to-person spread is so important in transmission of MRSA, strategies aimed at preventing transmission of the resistant strains are remarkably effective when strictly enforced. Ceftazidime resistance in Enterobacteriaceae results from point mutations within genes that encode widely prevalent and often transferable plasmid-mediated enzymes. In addition, mutations of these genes that allow hydrolysis of cephalosporins usually result in decreased activity against other drugs, including the penicillins and beta-lactamase inhibitors. Effective measures to control ceftazidime-resistant Enterobacteriaceae have as their cornerstone limiting administration of antibiotics that select for the emergence and spread of these mutations, especially ceftazidime. The importance of infection-control techniques in limiting the prevalence of ceftazidime-resistant Enterobacteriaceae is less well established. Methods that are informed by a detailed understanding of the molecular mechanisms of resistance and resistance spread offer the best hope for limiting dissemination of antibiotic-resistant bacteria in a cost-effective manner.199910456609
448030.9999Anaerobic bacteria and antibiotics: What kind of unexpected resistance could I find in my laboratory tomorrow? The purpose of this article is to set out some important considerations on the main emerging antibiotic resistance patterns among anaerobic bacteria. The first point concerns the Bacteroides fragilis group and its resistance to the combination of β-lactam+β-lactamase inhibitor. When there is overproduction of cephalosporinase, it results in increased resistance to the β-lactams while maintaining susceptibility to β-lactams/β-lactamase inhibitor combinations. However, if another resistance mechanism is added, such as a loss of porin, resistances to β-lactam+β-lactamase inhibitor combinations may occur. The second point is resistance to metronidazole occurring due to nim genes. PCR detection of nim genes alone is not sufficient for predicting resistance to metronidazole; actual MIC determinations are required. Therefore, it can be assumed that other resistance mechanisms can also be involved. Although metronidazole resistance remains rare for the B. fragilis group, it has nevertheless been detected worldwide and also been observed spreading to other species. In some cases where there is only a decreased susceptibility, clinical failures may occur. The last point concerns resistance of Clostridium species to glycopeptides and lipopeptides. Low levels of resistance have been detected with these antibiotics. Van genes have been detected not only in clostridia but also in other species. In conclusion, antibiotic resistance involves different mechanisms and affects many anaerobic species and is spreading worldwide. This demonstrates the need to continue with antibiotic resistance testing and surveys in anaerobic bacteria.201020971200
479740.9999Antibiotic resistance among clinically important gram-positive bacteria in the UK. The resistance of bacteria to antibiotics, particularly those used for first-line therapy, is an increasing cause for concern. In the UK, the prevalence of resistance to methicillin and mupirocin in Staphylococcus aureus, and to penicillin and macrolides in Streptococcus pneumoniae, appear to be increasing. There has also been an increase in the number of hospitals where glycopeptide-resistant enterococci are known to have been isolated. The increases in methicillin-resistant S. aureus and glycopeptide-resistant enterococci are due, in part, to the inter-hospital spread of epidemic strains. Although new quinolones and streptogramins with activity against Gram-positive bacteria (including strains resistant to currently available agents) are under development, there is no reason to believe that resistance to these agents will not emerge. The control of resistance in Gram-positive bacteria will require a multi-faceted approach, including continued and improved surveillance, a reduction in the unnecessary use of antibiotics, and the application of other strategies such as vaccination.19989777517
431450.9999Cephalosporin resistance among animal-associated Enterobacteria: a current perspective. Beta-lactam antimicrobials are an important class of drugs used for the treatment of infection. Resistance can arise by several mechanisms, including the acquisition of genes encoding beta-lactamases from other bacteria, alterations in cell membrane permeability and over expression of endogenous beta-lactamases. The acquisition of beta-lactamase resistance genes by both Salmonella and Escherichia coli appears to be on the rise, which may pose potential problems for the treatment of infections in both human and animal medicine. The prudent use of clinically important antimicrobials is therefore critical to maintain their effectiveness. Where possible, the use of newer generation cephalosporins should be limited in veterinary medicine.200515954857
483960.9999beta-Lactamases: protein evolution in real time. The evolution and spread of bacteria resistant to beta-lactam antibiotics has progressed at an alarming rate. Bacteria may acquire resistance to a given drug by mutation of pre-existing genes or by the acquisition of new genes from other bacteria. One ongoing example of these mechanisms is the evolution of new variants of the TEM and SHV beta-lactamases with altered substrate specificity.19989746943
979170.9999Beta-lactam resistance and the effectiveness of antimicrobial peptides against KPC-producing bacteria. Bacterial resistance is a problem that is giving serious cause for concern because bacterial strains such as Acinetobacter baumannii and Pseudomonas aeruginosa are difficult to treat and highly opportunistic. These bacteria easily acquire resistance genes even from other species, which confers greater persistence and tolerance towards conventional antibiotics. These bacteria have the highest death rate in hospitalized intensive care patients, so strong measures must be taken. In this review, we focus on the use of antimicrobial peptides (AMPs) as an alternative to traditional drugs, due to their rapid action and lower risk of generating resistance by microorganisms. We also present an overview of beta-lactams and explicitly explain the activity of AMPs against carbapenemase-producing bacteria as potential alternative agents for infection control.202236042694
431780.9999Development and spread of bacterial resistance to antimicrobial agents: an overview. Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The emergence and spread of multiply resistant organisms represent the convergence of a variety of factors that include mutations in common resistance genes that extend their spectrum of activity, the exchange of genetic information among microorganisms, the evolution of selective pressures in hospitals and communities that facilitate the development and spread of resistant organisms, the proliferation and spread of multiply resistant clones of bacteria, and the inability of some laboratory testing methods to detect emerging resistance phenotypes. Twenty years ago, bacteria that were resistant to antimicrobial agents were easy to detect in the laboratory because the concentration of drug required to inhibit their growth was usually quite high and distinctly different from that of susceptible strains. Newer mechanisms of resistance, however, often result in much more subtle shifts in bacterial population distributions. Perhaps the most difficult phenotypes to detect, as shown in several proficiency testing surveys, are decreased susceptibility to beta-lactams in pneumococci and decreased susceptibility to vancomycin in staphylococci. In summary, emerging resistance has required adaptations and modifications of laboratory diagnostic techniques, empiric anti-infective therapy for such diseases as bacterial meningitis, and infection control measures in health care facilities of all kinds. Judicious use is imperative if we are to preserve our arsenal of antimicrobial agents into the next decade.200111524705
486590.9999Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Colistin is an effective antibiotic for treatment of most multidrug-resistant Gram-negative bacteria. It is used currently as a last-line drug for infections due to severe Gram-negative bacteria followed by an increase in resistance among Gram-negative bacteria. Colistin resistance is considered a serious problem, due to a lack of alternative antibiotics. Some bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae members, such as Escherichia coli, Salmonella spp., and Klebsiella spp. have an acquired resistance against colistin. However, other bacteria, including Serratia spp., Proteus spp. and Burkholderia spp. are naturally resistant to this antibiotic. In addition, clinicians should be alert to the possibility of colistin resistance among multidrug-resistant bacteria and development through mutation or adaptation mechanisms. Rapidly emerging bacterial resistance has made it harder for us to rely completely on the discovery of new antibiotics; therefore, we need to have logical approaches to use old antibiotics, such as colistin. This review presents current knowledge about the different mechanisms of colistin resistance.201931190901
4860100.9999The rise of carbapenem-resistant Acinetobacter baumannii. Acinetobacter spp. are Gram-negative bacteria that have become one of the most difficult pathogens to treat. The species A. baumannii, largely unknown 30 years ago, has risen to prominence particularly because of its ability to cause infections in immunocompromised patients. It is now a predominant pathogen in many hospitals as it has acquired resistance genes to virtually all antibiotics capable of treating Gram-negative bacteria, including the fluoroquinolones and the cephalosporins. Some members of the species have accumulated these resistance genes in large resistance islands, located in a "hot-spot" within the bacterial chromosome. The only conventional remaining treatment options were the carbapenems. However, A. baumannii possesses an inherent class D β-lactamase gene (blaOXA-51-like) that can have the ability to confer carbapenem resistance. Additionally, mechanisms of carbapenem resistance have emerged that derive from the importation of the distantly related class D β-lactamase genes blaOXA-23 and blaOXA-58. Although not inducible, the expression of these genes is controlled by mobile promoters carried on ISAba elements. It has also been found that other resistance genes including the chromosomal class C β-lactamase genes conferring cephalosporin resistance are controlled in the same manner. Colistin is now considered to be the final drug capable of treating infections caused by carbapenem-resistant A. baumannii; however, strains are now being isolated that are resistant to this antibiotic as well. The increasing inability to treat infections caused by A. baumannii ensures that this pathogen more than ranks with MRSA or Clostridium difficile as a threat to modern medicine.201322894617
4834110.9999A retrospective view of beta-lactamases. The discovery of a penicillinase (later shown be a beta-lactamase) 50 years ago in Oxford came from the thought that the resistance of many Gram-negative bacteria to Fleming's penicillinase might be due to their production of a penicillin-destroying enzyme. The emergence of penicillinase-producing staphylococci in the early 1950s, particularly in hospitals, raised the question whether the medical value of penicillin would decline. The introduction of new semi-synthetic penicillins and cephalosporins in the 1960s began to reveal many beta-lactamases distinguishable by their different substrate profiles. In this period it was established that genes encoding beta-lactamases from Gram-negative bacilli could be carried from one organism to another on plasmids and also that penicillin inhibited a transpeptidase involved in bacterial cell wall synthesis. During the last two decades a number of these enzymes have been purified and the genes encoding them have been cloned. Much has now been learned, with the aid of powerful modern techniques, about their structures, their active sites, their relationship to penicillin-sensitive proteins in bacteria and to their likely evolution. Further knowledge may contribute to a more rational approach to chemotherapy in this area. Experience suggests that a need for new substances will continue.19911875234
9932120.9999Beta-lactam resistance mechanisms in gram-negative bacteria. Beta-lactam antibiotics are commonly used to treat a variety of bacterial infections. Gram-negative bacteria have evolved several resistance mechanisms including altered permeability and beta-lactamase production. New trends in resistance are emerging amongst clinical isolates which may reflect the choice of beta-lactam employed.19862856616
4859130.9999Nosocomial infection and its molecular mechanisms of antibiotic resistance. Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized.201626877142
4844140.9999Genetic basis of molecular mechanisms in β-lactam resistant gram-negative bacteria. Antibiotic-resistant bacteria are considered one of the major global threats to human and animal health. The most harmful among the resistant bacteria are β-lactamase producing Gram-negative species (β-lactamases). β-lactamases constitute a paradigm shift in the evolution of antibiotic resistance. Therefore, it is imperative to present a comprehensive review of the mechanisms responsible for developing antimicrobial resistance. Resistance due to β-lactamases develops through a variety of mechanisms, and the number of resistant genes are involved that can be transferred between bacteria, mostly via plasmids. Over time, these new molecular-based resistance mechanisms have been progressively disclosed. The present review article provides information on the recent findings regarding the molecular mechanisms of resistance to β-lactams in Gram-negative bacteria, including CTX-M-type ESBLs with methylase activity, plasmids harbouring phages with β-lactam resistance genes, the co-presence of β-lactam resistant genes of unique combinations and the presence of β-lactam and non-β-lactam antibiotic-resistant genes in the same bacteria. Keeping in view, the molecular level resistance development, multifactorial and coordinated measures may be taken to counter the challenge of rapidly increasing β-lactam resistance.202134119627
4832150.9999Antibiotic resistance of Pseudomonas species. Pseudomonas species are highly versatile organisms with genetic and physiologic capabilities that allow them to flourish in environments hostile to most pathogenic bacteria. Within the lung of the patient with cystic fibrosis, exposed to a number of antimicrobial agents, highly resistant clones of Pseudomonas are selected. These may have acquired plasmid-mediated genes encoding a variety of beta-lactamases or aminoglycoside modifying enzymes. Frequently these resistance determinants are on transposable elements, facilitating their dissemination among the population of bacteria. Mutations in chromosomal genes can also occur, resulting in constitutive expression of normally repressed enzymes, such as the chromosomal cephalosporinase of Pseudomonas aeruginosa or Pseudomonas cepacia. These enzymes may confer resistance to the expanded-spectrum beta-lactam drugs. Decreased cellular permeability to the beta-lactams and the aminoglycosides also results in clinically significant antibiotic resistance. The development of new drugs with anti-Pseudomonas activity, beta-lactam agents and the quinolones, has improved the potential for effective chemotherapy but has not surpassed the potential of the organisms to develop resistance.19863701534
4845160.9999The changing epidemiology of resistance. Antibiotic resistance is now a linked global problem. Dispersion of successful clones of multidrug resistant (MDR) bacteria is common, often via the movement of people. Local evolution of MDR bacteria is also important under the pressure of excessive antibiotic use, with horizontal gene transfer providing the means by which genes such as bla(CTX-M) spread amongst different bacterial species and strains. Beta-lactamase production is a common resistance mechanism in Gram-negative bacteria, and the rapid dissemination of novel genes reflects their evolution under the selective pressure of antibiotic usage. Many Enterobacteriaceae now carry broad-spectrum beta-lactamases such as CTX-M, with particular genotypes associated with different geographical regions. The spread of these enzymes has compromised the clinical utility of a number of beta-lactam classes and with the spread of genes such as bla(KPC), carbapenems may be increasingly compromised in the future. High-level fluoroquinolone resistance (mainly caused by gyrA mutations) has also been shown to be associated with CTX-M and CMY-type enzymes, commonly due to co-carriage on conjugative plasmids of the gene for the aminoglycoside-inactivating enzyme AAC-6(1)-Ib-cr and qnr genes (which confer low-level resistance), allowing the easy selection of gyrA mutants in the host strain. Resistance in Gram-positive bacteria is also widely distributed and increasing, with the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) blurring the distinction between hospital and community strains. Antibiotic use and environmental factors all have a role in the emergence and spread of resistance. This article reviews some of the new mechanisms and recent trends in the global spread of MDR bacteria.200919675017
4796170.9999The specter of glycopeptide resistance: current trends and future considerations. Two glycopeptide antibiotics, vancomycin and teicoplanin, are currently available for clinical use in various parts of the world, whereas a third, avoparcin, is available for use in agricultural applications and in veterinary medicine in some countries. Because of their outstanding activity against a broad spectrum of gram-positive bacteria, vancomycin and teicoplanin have often been considered the drugs of "last resort" for serious infections due to drug-resistant gram-positive pathogens. Glycopeptides had been in clinical use for almost 30 years before high-level resistance, first reported in enterococcal species, emerged. More recently, there have been disturbing reports of low- and intermediate-level resistance to vancomycin in strains of Staphylococcus aureus. A review of earlier reports reveals, however, that S. aureus strains with reduced susceptibility to glycopeptides were first identified >40 years ago. Such strains may occur in nature or may have developed low-level mutational resistance in response to the selection pressure of glycopeptide therapy. Of considerably greater concern is the possibility that vancomycin resistance genes found in enterococci may be transferred to more virulent organisms such as staphylococci or Streptococcus pneumoniae.19989684651
4833180.9998Emerging mechanisms of fluoroquinolone resistance. Broad use of fluoroquinolones has been followed by emergence of resistance, which has been due mainly to chromosomal mutations in genes encoding the subunits of the drugs' target enzymes, DNA gyrase and topoisomerase IV, and in genes that affect the expression of diffusion channels in the outer membrane and multidrug-resistance efflux systems. Resistance emerged first in species in which single mutations were sufficient to cause clinically important levels of resistance (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). Subsequently, however, resistance has emerged in bacteria such as Campylobacter jejuni, Escherichia coli, and Neisseria gonorrhoeae, in which multiple mutations are required to generate clinically important resistance. In these circumstances, the additional epidemiologic factors of drug use in animals and human-to-human spread appear to have contributed. Resistance in Streptococcus pneumoniae, which is currently low, will require close monitoring as fluoroquinolones are used more extensively for treating respiratory tract infections.200111294736
4817190.9998Relationship Between Biofilm Formation and Antimicrobial Resistance in Gram-Negative Bacteria. Gram-negative microorganisms are a significant cause of infection in both community and nosocomial settings. The increase, emergence, and spread of antimicrobial resistance among bacteria are the most important health problems worldwide. One of the mechanisms of resistance used by bacteria is biofilm formation, which is also a mechanism of virulence. This study analyzed the possible relationship between antimicrobial resistance and biofilm formation among isolates of three Gram-negative bacteria species. Several relationships were found between the ability to form biofilm and antimicrobial resistance, being different for each species. Indeed, gentamicin and ceftazidime resistance was related to biofilm formation in Escherichia coli, piperacillin/tazobactam, and colistin in Klebsiella pneumoniae, and ciprofloxacin in Pseudomonas aeruginosa. However, no relationship was observed between global resistance or multidrug-resistance and biofilm formation. In addition, compared with other reported data, the isolates in the present study showed higher rates of antimicrobial resistance. In conclusion, the acquisition of specific antimicrobial resistance can compromise or enhance biofilm formation in several species of Gram-negative bacteria. However, multidrug-resistant isolates do not show a trend to being greater biofilm producers than non-multiresistant isolates.201930142035