The Antibiotic Epidemic Antibiotic Resistance

Antibiotic Resistance: Surviving An Uncertain Future

Antibiotic use can damage and weaken a healthy immune system and our reliance on them has been a double-edged sword. In fact, there are many, many powerful plant-based antimicrobials, scientifically tested, that can step up to the plate and help us face the growing threat of resistant bacteria. And you'll find them in this new eBook: The Antibiotic Epidemic: How to Fight Superbugs and Emerging Bacteria with Miracles from Mother Earth. This Ebook Shows You The Many Powerful Plant-based Antimicrobials And Provides Recipes To Help Diminish The Need For Antibiotics. ebooThis can be your guide during the coming antibiotic apocalypse.

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Measuring Antibiotic Resistance

Laboratory testing for antibiotic resistance is generally done by using phenotypic assays, although for an increasing number of cases, genotype-based assays can provide rapid information (61,62). procedure to obtain reports, such as regular telephone calls or visits to laboratories. Passive surveillance relies on clinicians or laboratories to contact the organization doing the surveillance. Because there are many different permutations of active and passive surveillance, before applying surveillance data to a given population, the clinician or public health practitioner must understand the source of the data and the type of surveillance system (68). Notifiable disease reporting, laboratory-based surveillance systems, and clinics with internal tracking systems may all obtain information about antibiotic resistance but because the methods of data collection differ, estimates of resistance often differ as well. No matter where surveillance data come from whether population based systems...

Background And Epidemiology Of Resistant Pathogens

Resistance among microorganisms is a predictable result of the Darwinian selective pressure of antimicrobial agents (10). The first description of a mechanism for antibiotic resistance was published in 1940, when Abraham and Chain described an enzyme in E. coli that could hydrolyze penicillin (11,12). Since then, the understanding of resistance at the molecular level has increased dramatically unfortunately, at the same time, the number of pathogens exhibiting antimicrobial resistance has also increased dramatically. The public health impact of drug resistance derives from a combination of the magnitude of the resistance and its implications for morbidity and mortality. Magnitude of Antibiotic Resistance

Factors Promoting Antimicrobial Resistance And Measures To Control Its Spread

Antibiotic exposure is the main factor promoting antibiotic resistance in both populations and individuals, although crowding and other risk factors also contribute selective pressure for resistance and encourage its spread (Table 3) (8,12,71,72). We have categorized resistant pathogens as foodborne, hospital-acquired, or community-acquired. While appropriate measures to curb development of resistance have different In the dense microcosm of the hospital, antibiotics are frequently used and bacteria may be readily passed from one patient to the next (46,80-82). Antibiotic resistance develops in response to the heavy use of antimicrobial agents in hospitals, and resistance to many drugs has been closely correlated with previous use of that drug. One particular concern is patients who have had exposure to vancomycin and thus are more apt to develop infections with vancomycin-resistant Enterococcus (VRE) (42). Once the selective pressure of antibiotic exposure causes susceptible...

Issues In Antimicrobial Treatment

Single vs multiple antimicrobial therapy Pneumonia is generally regarded as being easy to treat. Therefore, in most cases acceptable cure rates can be obtained using a single antibiotic. However, nosocomial pneumonia, especially in critically ill patients, usually requires combination antibiotic therapy. The rationale for this is that antibiotics that act by different mechanisms could serve to expand antibiotic coverage, reduce toxicity from lower individual doses of the drug, or act synergisti-cally and potentially lower the development of antibiotic resistance. The most work in this area has examined only immunocompromized hosts, and it may not be appropriate to extrapolate that evidence to other settings. Among the different agents, aminoglycosides have been shown to be particularly effective in empirically treating severe nosocomial pneumonias and in treating pneumonia due to Pseudomonas aeruginosa, Acinetobacter sp., and -lactamase producing Gram-negative organisms.

Oxidative Stress in Bacteria

The genetic response to oxidative stress has been studied extensively in E. Coli. The synthesis of over 80 proteins is induced upon exposure to H2O2 and O -, and two transcription factors have been identified. Firstly the system OxyR which is activated by H2O2, resulting in the formation of an intracellular disulfide bond, that then switches on several genes encoding for antioxidant functions such as catalase. During aerobic growth, OxyR acts homeostatically to regulate cellular H2O2 levels. Secondly the transcription factors SoxR S are induced by superoxide anions or nitric oxide and activate expression of genes, the products of which are involved either in protection from oxidative stress or repair of ROS-mediated damage. The SoxR protein is activated by oxidation of its 2Fe-2S component and stimulates the SoxS gene. The SoxS protein then induces transcription of at least 15 genes encoding antioxidant functions, e.g. SOD, metabolic functions and antibiotic resistance by activation...

Immunotherapy Of Specific Bacterial Infections

No antisera directed against the polysaccharides or proteins of any of the hemolytic streptococci have been developed to date. In studies of the use of various intravenous immunoglobulin (IVIG) preparations in the prevention and treatment of sepsis in low-birth-weight and other neonates, there appeared to be a small, but significant effect on decreasing the mortality rate associated with sepsis (8,9). Group B streptococci are an important cause of neonatal sepsis, but these studies did not specifically address these organisms, and it is as yet unclear whether the use of standard IVIG preparations would prevent or augment the treatment of serious group B streptococcal infections. Group B streptococci can also cause serious disease in adults, especially those with underlying diabetes, cirrhosis, and malignancy, but these infections have not posed a threat in terms of antibiotic resistance, and it would seem unlikely that hyperimmune antisera to group B streptococcal antigens would...

Clinical Relevance

Bacteria possessing antibiotic resistance determinants arise in LTCFs by one of two ways. The transfer of infected or colonized patients from hospital to LTCF is believed to be the primary way resistant bacteria are introduced into nursing facilities (nursing homes). A contemporary example of this is the spread of methicillin-resistant Staphylococcus aureus (MRSA) to LTCFs from tertiary care centers (17). In this study, a single asymptomatic carrier passed MRSA to 24 veterans in a skilled care unit. Second, the excessive and inappropriate use of antibiotics can select for mutations in bacterial gene(s) that confer a selective advantage. Examples of this are (1) the selection of mutations in -lactamase genes that confer resistance to third-generation cephalospor- ins (18,19), (2) the selection of quinolone-resistant bacteria with mutations in gyrA and gyrB or parC (20,21), and (3) mutations in dhfr, which confer resistance to TMP SMX (22). Once endemic to an LTCF, the antibiotic...

Infection Control And Antibiotic

The Society for Health Care Epidemiology has drafted recommendations to help control antibiotic resistance in LTCFs and cross-infection include antibiotic restriction practices, surveillance, nontreatment of asymptomatic bacteruria, minimizing topical antibiotics, hand washing, and barrier precautions for wound care (108). We propose that, for LTCFs, the following additional items be specifically stressed (1) education, (2) surveillance, (3) antibiotic control, and (4) immunization.

Arch G Mainous III and Claire Pomeroy

The rapidly expanding challenge of antibiotic resistance impacts on patients across the globe. As the new millennium dawns, drugs for the treatment of many illnesses are becoming limited, more expensive, or in some tragic cases nonexistent. As outlined in the preceding chapters, all medical practitioners must be aware of the implications of drug resistance when prescribing therapy. In its 1992 report, the Institute of Medicine identified antibiotic resistance as one of the emerging disease threats. Tuberculosis and cholera organisms once thought to be nearly eradicated have developed drug-resistant strains and threaten the health of millions of people. Bacteria such as pneumococcus, enterococcus, and Staphylococcus aureus have developed resistance at a rapid rate and across multiple antibiotics. It was reported in 1995 that antimicrobial resistance among six common bacteria in U.S. hospitals added more than 600 million per year in direct hospital charges (1). It is becoming ever...

Antibiotics In Medical Settings For Diseases Not Traditionally Viewed As Infections The Example Of Cardiovascular

An exciting new area of research is the possible etiologic role of infections in the development of illnesses not traditionally viewed as infectious. The documentation of H. pylori as the cause of peptic ulcer disease has led to the use of antibiotics in many patients. The recognition that HHV-8 is the cause of Kaposi's sarcoma suggests that cancers may require treatment with antiviral agents. Currently, infections have been hypothesized to play a role in the development of diseases ranging from neuropsychiatric problems to multiple sclerosis. As more and more of these diseases are found to be due to infection, more and more people will receive courses of antimicrobial therapies, in some cases for prolonged periods of time. The impact of these new therapeutic choices on the development of antibiotic resistance will become clearer over the next few years. The effectiveness of prophylactic antibiotic therapy in the primary prevention of CHD has not been evaluated prospectively. Clinical...

Antimicrobial Susceptibility

Most Aeromonas spp. are susceptible to a number of antibiotics, such as tetracyclines, trimethoprim-sulfamethoxazale, aminoglycosides, cephalosporins, and the quinolones. However, emerging antibiotic-resistance properties of aeromonads directed towards these antibiotics are being pinpointed (48). Aeromonas schubertii, A. jandaei, and A. veronii biotype veronii, each associated with human infections or obtained from human clinical samples, have been found to exhibit various levels of antibiotic resistance towards ampicillin, ampicillin-sulbactam, cefazolin, imipenem, piperacillin, and ticarcillin (49). The production of chromosome-mediated P-lactamases by Aeromonas spp. threatens therapy against Aeromonas infections, and therefore public health (50). Even aeromonads isolated from sewage possess a transferable tetracycline R-plasmid that can easily spread to clusters of Aeromonas spp. found in humans (51).

Plasmids of Legionella

Legionella Genome

Two of the three sequenced L. pneumophila strains carry plasmids that might play a role either in adaptation to the environment or in virulence as both encode putative virulence factors, mobile genetic elements and antibiotic resistance genes. In strain Paris a 132 kb plasmid and in strain Lens a 60 kb plasmid was identified, both of which seem to be single copy plasmids. These plasmids contain a 24 kb and 30 kb gene cluster, respectively, encoding homologs of Tra proteins (Figure. 1.6). Furthermore several mobile elements like transposases and phage-related proteins are present and about half of the genes code proteins of unknown function. Both plasmids also encode a paralog of CsrA a protein known to act as repressor of transmission traits of L. pneumophila and as activator of replication (Molofsky and Swanson 2003), revealing the question whether these plasmids are implicated in virulence. The plasmid identified in strain Paris carries many genes coding proteins probably conferring...

Genetically Engineered Animals

Recombination between homologous sequences in the vector and target DNAs results in the substitution of the vector for the genomic DNA. A selection marker, such as a bacterial antibiotic resistance gene, is also normally included in the targeting vector, to enable homologous recombinants to be selected. To knockout a gene it is not necessary to delete the whole gene of interest, only to inactivate its function, which may be achieved by deleting a small section of the gene, such as the promoter and the first part of the coding sequence.

Antibiotic Control Policies

Restriction of use of specific antibiotics and antibiotic classes has been effective in altering patterns of resistance in individual institutions. For example, in a 500-bed university-affiliated community hospital, 30-40 of nosicomial Klebsiella infections were cephalosporin resistant in 1995 (34). An antibiotic control policy was developed that, in general, excluded the use of cephalosporins, without prior approval of an infectious disease expert. In one year, an 81 reduction in hospital-wide cephalosporin use was documented, paired with a 140 increase in imipenem use. Ceftazidime-resistant Klebsiella was reduced by 36 in nosicomial infections, but this was accompanied by an increase in imipenem-resistant Pseudomonas aeruginosa. Overall, there was a reduction in multiply resistant pathogens, but the continued impact beyond this 1-yr intervention on antibiotic resistance is unknown.

Expanding Use Of Antibiotics In Nonmedical Settings Animal Feed

A great deal of interest has been generated in the link between the use of antibiotics in food animal feeds and the extent to which the practice contributes to the development of antibiotic resistance. Evidence has continued to accumulate suggesting a relationship between the use of antibiotics in animal feed as a growth promoter and the development of resistant pathogens, particularly vancomycin-resistant enterococci (VRE) (34). Antibiotics added to animal feed not only reduce the normal intestinal

Failure Of Infection Control Procedures

The CDC has developed a plan to respond to the threat of emerging infectious diseases including the problem of antibiotic resistance (23). A system of surveillance and response has been developed, including the Epidemiology and Laboratory Capacity (ELC) program, the Emerging Infections Programs (EIP) and provider based sentinel networks. A specific charge of the ELC program is to track antimicrobial resistance. EIP priorities include retarding the emergence and transmission of antibiotic resistance. The World Health Organization has a WHONET surveillance systems and a program for antimicrobial resistance monitoring (ARM), and continues its efforts in monitoring drug resistant tuberculosis on a global basis. It is critical that all practitioners interact with these programs, especially by reporting to their local health departments (24).

Changing To Promote Optimal Antibiotic

Physicians and other health care providers claim awareness of the problem of antibiotic resistance, created by the overuse of antibiotics. However, given the fact that inappropriate antibiotic use continues, this simple awareness is not sufficient to affect prescribing behavior. Several strategies have been applied to improve antibiotic prescribing in the outpatient and inpatient settings, which focus on the system, provider, and patient (see Table 2). These strategies are often implemented in closed health care systems, and consist of tightly controlled interventions. However, when these interven-

Does Plasma Membrane Glow When Current Is Supplied

In addition to genes for antibiotic resistance, several other reporter genes are used to detect recombinant DNA in host cells. Scientists have created several artificial vectors that include restriction sites within the lac operon (see Figure 13.17). When the lac operon is inactivated by the insertion of foreign DNA, the vector no longer carries its function into the host cell. Other reporter genes that have been used in vectors include the gene for luciferase, the enzyme that causes fireflies to glow in the dark this enzyme causes host cells to glow when supplied with its substrate. Green fluorescent protein, which normally occurs in the jellyfish Aequopora victoriana, does not require a substrate, but emits visible light when exposed to ultraviolet light, and is now widely used as a genetic marker, as described at the beginning of this chapter. Many commonly used plasmid vectors contain only a single reporter gene for antibiotic resistance, which does not contain a restriction site....

Genetic Factors Involved In Virulence

Production of toxin by V. cholerae O1 strains seems to be regulated by three other genes recently reported but not yet well characterized. These include htx locus, ltx locus, and tox-1000 locus genes mutation of genes in these loci either increase or decrease the production of toxin by V. cholerae O1 strains. In addition, some plasmids present in V. cholerae O1 have been reported to influence the toxin production. These include C compatibility plasmids, which regulate antibiotic resistance, and sex factor P the former increase and the latter decreases toxin production in V. cholerae 569B (85).

Genome and Plasmid

Several reports indicated the presence of plasmids of different sizes in Lm strains (9a-11). Some of these plasmids are cryptic (9a), while others carry antibiotic resistance (11) and cadmium resistance genes (10). No association of these plasmids with Lm virulence has been established so far.

Clinical Application

To minimize the emergence of drug-resistant viral mutants we need to capitalize on the lessons learned in handling the problem of antibiotic resistance in bacteria. Antiviral agents should be used only when absolutely necessary, but administered in adequate dosage. Certain Iifesaving drugs may need to be retained for designated diseases only, and or as replacement therapy following the emergence of resistance to the standard drug. Combined therapy, preferably using agents with distinct modes of action, minimizes the probability of emergence of resistant mutants. Furthermore, by allowing one or both drugs to be given in lower dosage, combined therapy can reduce the incidence of toxic side effects. In certain instances, particular drug combinations display synergism, as has been observed when interferon a is combined with acyclovir or zidovudine, for example.

Bacterial Plasmids

The most common forms of genetically altered DNA are bacterial plasmids, small circular molecules separate from the cell chromosome. Plasmids may be altered to serve as appropriate vectors (carriers of genetic material) for genetic engineering, usually containing an antibiotic resistance gene for selection of only those cells that have incorporated the DNA. Once the cell has incorporated the plasmid, it acquires the ability to produce any gene product encoded on the molecule.

Knockout strategy

The basic technique for generating a knockout mutation begins with generation of a targeting vector that consists of fragments of the gene flanking the sequence that is to be deleted. Usually, in order to completely inactivate a gene, the targeted region includes the promoter and exons that are essential for mRNA production and the synthesis of functional protein. Deleted genetic regions are replaced with selectable markers such as antibiotic resistance genes like neomycin-resistance (neomycin phosphotransferase II) (Figure 20.2).

Conclusions

Although specific antibiotic selection and restriction policies in the hospital setting are important in altering microbial susceptibility patterns, an overall reduction in antibiotic use in a wider population, the outpatient setting, is more likely to significantly impact antibiotic resistance. Education of providers, the development and implementation of clinical practice guidelines, audit and feedback activities, and multifaceted interventions have all demonstrated an effect in altering antibiotic prescribing in a research setting. However, the ability to translate these research activities into clinical practice and on a wider basis affect antibiotic use, has not been consistently accomplished. In addition, the use of the pneumococcal vaccine has not been widely adopted, although infection with S. pneumoniae continues to threaten various populations. Addressing antibiotic use and resistance is one of the most urgent priorities in confronting emerging infectious disease threats...

Salmonella

There is concern with regard to the distribution of multi-drug resistant Salmonella within the food chain. It is commonly believed that the exploitation of antibiotics as animal growth promoters has led to the prevalence of resistant servors. It is now emerging that the main source of antibiotic resistance is in humans with the strains being introduced by direct contact with animals being less significant (Snary et al., 2004). The possible use of antibiotics to suppress plant pathogens has been considered as a possible route by which Salmonella and other human pathogens can acquire resistance. Although this may seem unlikely it is interesting to note that streptogramin-resistant Enterobacter faecium has been previously isolated from bean sprouts (Snary et al., 2004).

Enterococcus

Because of their ability to survive harsh conditions, enterococci can persist in the environment (31,32). Adherence to host structures (cardiac valves, renal epithelial cells) facilitates the development of endocarditis and urinary tract infection. Antibiotic resistance plays a role in the ability of enterococci to cause superinfection in the presence of broad-spectrum antimicrobials.

Acute Otitis Media

If antibiotics are selected for the management of acute suppurative otitis media, selection of an agent should provide coverage for the two most common organisms, S. pneumoniae and H. influenzae. Second, the duration of antibiotic treatment should be as short as possible to minimize the development of antibiotic resistance. In a metaanalysis of trials that compared short-duration antibiotic therapy with the traditional 10-d course, no benefit was found of using longer courses of treatment (53). A 5-d course of antibiotics should be sufficient for treatment. In addition to short-course therapy, a single intramuscular dose therapy of ceftriaxone has been shown to have benefit equal to that of longer courses of amoxicillin (54), cefaclor (55), or trimethoprim-sulfamethoxasole (56) for the treatment of acute suppurative otitis media. Where antibiotic resistance to S. pneumoniae is high or where patient compliance is an issue, ceftriaxone may be a viable alternative. Second, the...

Procedure

Colon Arteries

Perioperative antibiotics are used routinely, but there is no benefit in administering more than one or two doses postoperatively. Overuse of antibiotics in a prophylactic setting leads to antibiotic resistance. If infection develops, antibiotics are restarted and are tailored to the specific source of infection.

Infections

Lung Medical Terminology

The incidence of tuberculosis (TB) has increased in recent years, along with the increase of AIDS and the appearance of antibiotic resistance in the organism that causes the disease, Mycobacterium tuberculosis (MTB). (This organism, because of its staining properties, also is referred to as AFB, meaning acid-fast bacillus.) The name tuberculosis comes from the small lesions, or tubercles, that appear with the infection. The symptoms of TB include fever, weight loss, weakness, cough and, as a result of damage to blood vessels in the lungs, hemoptysis, the coughing up of sputum containing blood. Sputum analysis is used to isolate, stain, and identify infectious organisms. Accumulation of exudate in the alveoli may result in consolidation of lung tissue. The tuberculin test is used to test for tuberculosis infection. The test material that is used, tuberculin, is made from byproducts of the tuberculosis organism. PPD (purified protein derivative) is the form of tuberculin commonly used.

Cellulitis

Treatment in most cases is directed against streptococci and S aureus. In the afebrile, immunocompetent patient who has a small area of involvement, oral antibiotic therapy consisting of dicloxacillin, cephalexin, clinda-mycin, or erythromycin can be considered if the community antibiotic-resistance profiles are favorable 4 . In immunocompetent patients who are more severely ill, initial parenteral antibiotics that can be used include nafcillin, oxacillin, or cefazolin 4 . The emergence of methicillin resistance in S aureus isolates from the community needs to be considered because these organisms are resistant to beta-lactam antibiotics, such as penicillins and cephalosporins. Agents such as trimethoprim-sulfamethoxazole, doxy-cycline or minocycline, clindamycin, linezolid, vancomycin, and daptomycin often are used to manage community-acquired MRSA skin infections. Immobilization and elevation of involved areas and treatment of underlying predisposing conditions is recommended....