The Antibiotic Epidemic Antibiotic Resistance
There are four major antibiotic resistance mechanisms There are two types of antibiotic resistance in clinical isolates intrinsic resistance, which is an intrinsic property of a bacterial species that makes them resistant to an antibiotic, and acquired resistance, where a population of bacteria that were initially sensitive to an antibiotic become resistant. Acquired resistance can be due to the acquisition of mutations in the gene that encodes the cellular target of the antibiotic that, for example, reduces antibiotic binding, or by the acquisition of a plasmid that encodes a resistance gene. Intrinsic resistance, since it is predictable, is by far the easiest to overcome however, acquired resistance is a serious threat to the continued existence of many antibiotic treatments. Plasmids are extra-chromosomal genetic elements that replicate independently of the bacterial circular genome and can be transferred from cell to cell by the process of bacterial conjugation. Plasmids...
Homologous recombination may involve either single or double crossover events. To insertionally inactivate a chromosomal gene by a single crossover event an internal fragment of the gene to be inactivated is cloned into a suicide vector, that is, a vector that is unable to replicate in C. perfringens. An antibiotic resistance gene that is expressed in C. perfringens is added and the resultant plasmid used to transform C. perfringens to antibiotic resistance. The only way in which resistant transformants can be obtained is if the plasmid has been integrated into the chromosome by homologous recombination with the chromosomal gene. The advantages of this method are that the recombination efficiency is greater because only a single crossover event is required. The disadvantages are first that it requires an internal gene fragment, limiting the recombination efficiency, and second, that wild-type genes can be regenerated from the mutants by homologous recombination between the two gene...
With the realisation that hospitals are populated both by 'sick patients', with underlying medical conditions that may make them more susceptible to infection, and by 'fit bacteria' that are capable of causing serious infections and often carry antibiotic resistance genes, it is easy to see why the UK is confronted with a serious problem of healthcare-associated infections (HAIs) caused by 'superbugs'. This term appeared in newspapers in the UK in 1985 in the context of stories about the agricultural use of antibiotics leading to the evolution of antibiotic-resistant pathogenic bacteria. From about 1997, the term began to be used widely, both in broadsheet newspapers and by politicians, in stories concerning methicillin-resistant Staphylococcus aureus (MRSA). The use of the term superbugs implies that there are ordinary 'bugs' which, although capable of causing infections, are not a threat, and then there are superbugs, such as Clostridium difficile (C. difficile)
ESBL-producing isolates typically display resistance to other classes of antibiotics as well as beta-lactams, due to the acquisition of additional antibiotic-resistance genes by these isolates. This reduces the options for treating hospital patients infected with CTX-M isolates to the carbapenems, which have been termed the 'antibiotics of last resort'. The recent appearance of bacteria producing carba-penemases (beta-lactamases that can inactivate carbapenems) means that there is no reliable antibiotic left to treat these infections, with potentially devastating consequences for healthcare systems worldwide (Schwaber and Carmeli, 2008).
Infection control measures must be more available in the community, along with better education of the public, in order to prevent the acquisition and prevention of infections. This will open up opportunities for innovative products such as medical textiles for use in the community. Dressings that can detect a wound infection in an elderly person living alone in their own home and then send a wireless signal to a community infection control team may be an example of what will become common in the next decade. This will allow rapid point-of-care diagnostic tests to be carried out, both to identify the pathogen and detect any antibiotic resistance properties, allowing treatment of the infection to be commenced during a single home visit.
Antibiotics that affect Propionibacterium acnes are a standard treatment for acne but antibiotic resistance is becoming prevalent. A preliminary study of 126 patients showed that topical 2 essential oil of Ocimum gratissimum (thymol chemotype) in a hydrophilic cream base was more effective than 10 benzyl peroxide lotion at reducing the number of lesions when applied twice daily for 4 weeks (Orafidiya et al., 2002).
Although infection with Shigella generally is self-limited and responds to supportive care, antibiotic therapy is indicated because it shortens the duration of illness and shedding and consequently reduces the risk of transmission. Antibiotic resistance is a worldwide concern and growing problem for enteric bacterial pathogens. The treatment of choice is a fluoroquinolone when the antibiotic susceptibility of the organism is unknown5 (Table 76-2). Cephalosporins or azithromycin can be used in the management of pediatric shigellosis. Rifaximin is likely to be effective in the treatment of milder forms of shigellosis and is effective at preventing infection with S. flexneri 6 Antimotility agents are not recommended because they can worsen dysentery and may be related to the development of toxic megacolon. No vaccines are licensed currently for the prevention of shigellosis.
Routine antibacterial prophylaxis is controversial and has been attempted primarily with sulfamethoxazole trimethoprim (SMZ-TMP) and quinolones. SMZ-TMP offers improved prophylaxis for gram-positive organisms compared with quinolones while quinolones are more effective prophylaxis against gram-negative infections. The 2002 Infectious Diseases Society of America (IDSA) guidelines for the use of antimicrobial agents in cancer do not recommend the use of these agents for routine prophylaxis.19 Reasons for this recommendation include the lack of a clear benefit on mortality rates and concerns regarding increasing antibiotic resistance. One exception is that SMZ-TMP is recommended for prophylaxis of Pneumocystis jirovesi ( formerly Pneumocystis carini) pneumonitis (PCP) in all at-risk patients (i.e., bone marrow transplant recipients, AIDS), regardless of the presence of neutropenia.
The most common pathogens vary with the type of pneumonia, and they are listed in Table 71-1. M. pneumoniae lack a cell wall therefore, -lactam antimicrobials have no activity against this organism. The atypical organisms have not changed in recent years with respect to antibiotic resistance. -lactamase production in H. influ-enzae has remained relatively steady over the last 5 to 10 years and the rate is approximately 35 26 S. pneumoniae has developed resistance mechanisms against many classes of antimicrobials and the mechanisms include
ROOD is a Reader in Microbiology at Monash University in Melbourne, Australia. He is a Fellow of both the Australian Society for Microbiology and the American Academy of Microbiology. His research career has focused on the development of the genetics of Clostridium perfringens, the use of molecular genetics to study the regulation of toxin production and the pathogenesis of clostridial myonecroses, and the genetic analysis of clostridial antibiotic resistance determinants.
Antibiotic resistance determinants and transposons from both Clostridium perfringens and Clostridium difficile have been reviewed in recent years.1-3 However, since these reviews were published there have been many advances in knowledge in this area. This chapter will focus on the most recent findings, as well as summarizing the earlier work. Where possible, our emphasis will be on comparisons between the C. perfringens and C. difficile antibiotic resistance determinants and transposons.
As a result of extensive cloning, hybridization and DNA sequence analysis, our knowledge of antibiotic resistance determinants from C. perfringens and C. difficile has grown considerably in recent years. The latest studies on tetracycline resistance in C. perfringens20 have proven to be interesting as they have shown that, for reasons which are not yet known, virtually all tetracycline resistant isolates carry two resistance genes, which is most unusual. In addition, the finding that a ei(M)-like determinant exists in C. perfringens is significant
Because the most frequent cause is viral, bronchitis has often been overtreated with antibiotics, which would be a preventable source of antibiotic resistance. However, in patients with a productive cough persisting beyond 10 to 14 days, treatment with antibiotics may be indicated to treat bacterial co-infection, especially in smokers or in patients with underlying pulmonary disease. In a study of community-acquired acute bronchitis in France, polymerase chain reaction (PCR) testing revealed that 4.1 of patients were infected with Chlamydia pneumoniae and 2.3 with Mycoplasma pneumoniae (Gaillat et al., 2005).
Relapse is suggested by the returning of symptoms 3 to 21 days after stopping met-ronidazole or vancomycin. Since antibiotic resistance is not a factor in relapse, most relapses usually respond to another course of either metronidazole or vancomycin. Currently, metronidazole is recommended for treatment of the first recurrence, while vancomycin pulse dosing (125 mg orally every 3 days for 3 weeks) or tapered dosing (125 mg orally four times daily for 10-14 days, then 125 mg orally twice daily for 7 days, then 125 mg orally daily for 7 days) is recommended for treatment of subsequent recurrences.