Prophylactic use of antimicrobials – a debatable issue

An ancient and quiet honourable practise has been the use of preventive medicine. For example, the ancient Chinese use to pay their doctors while they remained healthy, however as soon as they felt sick this payment would not be given. The effectiveness of antibiotics as a prophylactic means for protecting healthy individuals exposed to pathogenic bacteria, preventing the development of an infection in chronically ill patients and preventing an infection in patients who undergo surgery is a debatable issue. Many surgeons reported significant reductions in post-operative infection following antibiotic use, and a few did not even reported infections for a period of twenty years. Despite this success, prophylaxis presents certain hazards, including the evolution of antibiotic resistance, superinfections and drug side effects, for the individual patient and for the general public. Therefore, physicians have broad views on the responsible preventive use of antibiotics. However, antimicrobial prophylaxis (AP) should be confined to specific well-accepted evidence for the prevention of excess costs, toxicity and antimicrobial resistance in order to effectively prevent infections. Initial or secondary (recurring prevention or reactivating infections) prophylaxis may also be regarded as primary (prevention of initial infections) or may be administered to prevent infection by killing a colonising organism. Patients should know in detail the potential risks and benefits of AP. The potential risks are allergic reactions with the use of antibacterial agents that can be serious or life-threatening, and clostridium difficile colitis. The risk of tendinitis, including the rupture of the tendon of Achilles should be alerted to patients taking fluoroquinolones.

The pros and cons of using antimicrobials as a prophylactic.

  1. THE PROS: In the diagnosis of life-threatening acute bacterial infections, surgical infectious diseases and if there is an effective use of antimicrobials as prophylaxis, antibiotics can have many benefits.

In bacterial infections: In acute bacterial infections, which were highly mortal before introduction of antibiotics, the benefits of antibiotics as prophylactics is most clearly indicated. Mortality in endocarditis was about 100% prior to 1990 and about 20% total in 2010 although the death rate is usually caused not by unsuccessful antibiotic therapy but by cardiac failure or embolic complications. In bacterial meningitis in 1990, the mortality rate was reduced to 8% to 20% in 2010 and acute osteomyelitis mortality decreased from 50% to less than 1%. Many other infections, in both individual patients and others within the community, have significantly reduced morbidity and serious effects of spraying. In high-risk patients, this included the use of antibiotic prophylaxis for bacterial meningitis. During the systemic inflammatory response (SIR) stage of the infection, the early initiation of broad- spectrum antibiotics was proved critical for preventing the development of sepsis. When appropriate antibiotics are prescribed early in the surgical sepsis, mortality is significantly reduced.

In surgical site infections: Although the technique is still less than good surgical and aseptic technique, the risk of surgical site infection is considerably decreased by antibiotic prophylaxis in high-risk surgical patients such as operations over 2 hours, abdominal procedures, endogenous or exogenous contamination and co-morbidity. The choice of antibiotics depends on the organisms that are most likely to be affected; the kind of operation; the probability of resistance development and the financial cost involved. In felines, the rate of postoperative infections was reduced in the course of the optional orthopaedic surgery by preoperative antibiotic prophylaxis. Therefore, it is usually advisable to treat routine perioperative prophylactic antibiotics, even if numerous orthopaedic operations are categorised as clean. Orthopaedic procedures normally last longer than 90 minutes and the potential infection may be influenced by local wound factors like implants and tissue trauma. In the presence of implants, bone and joint infections are very difficult to treat, increase morbidity and may adversely affect the result. Cefazolin is currently seen as a choice antibiotic because of its outstanding effectiveness, low toxicity and reasonable costs against most surgical wound pathogens. The first dose should be given at a concentration of 22 mg/kg 30–60 minutes before surgery. The dose is usually recommended to be repeated every 90–120 minutes, but there is evidence that the frequency is enough every three hours.

The selection criteria of the antibiotic are:

  • The most prone bacteria that could cause infection should be identified. A prophylactic against frequently found skin bacteria (skin flora) is used when only an incision in the skin is made. An antibiotic is chosen to treat both the skin and the mucosal flora if the mucosal incision is involved.
  • Chemical and drug toxicity characteristics.
  • The least likely antibiotic that is required for serious infections is chosen if different antibiotics are equally helpful for prophylaxis. This helps prevent antibiotic resistance from developing.
  • Sensitivities specific to the environment of the specific hospital. Some hospitals may be very frequent with methicillin-resistant infections, while vancomycin or clindamycin-resistant infections in other hospitals may be more frequent.
  • CONS: The drawbacks of prophylactic antimicrobials are shown by side effects, resistance development and opportunistic pathogens.

Side effects: Their ability to cause serious or fatal adverse reactions sometimes provides a reason to limit the use of antibiotic agents for true therapeutic indications. For example, the most commonly used antibiotics for UTI prevention are nitrofurantoin, trimethoprim/sulfamethoxazole (TMP / SMX), but these drugs have negative reactions in children. Gastrointestinal disturbance, skin reactions such as urticaria, maculopapular rash are the common adverse reactions to nitrofurantoin. Almost exclusively because of sulfamethoxazole, most commonly dermal, adverse events related to trimethoprim/sulfamethoxazole. Serious side effects are extremely rare and mostly reversible when treatment is discontinued but they do exist. The long-term use of low-dose urinary prophylaxis antibiotics is therefore not completely safe. While adverse reactions existed in children to these medications, the lower dose of prevention and the lack of significant co-morbidities and medicinal interactions in children are much less common in children than in adults. In 1% of patients, penicillin causes death from type I anaphylactic shock in sensitive allergic patients and have other harmful consequences. High dose of penicillin may be associated with serum sickness (type III reaction), penicillin, thrombocytopenia, and haemolytic anaemia from cytotoxic antibodies. There is 10 percent cross-sensitivity between the derivatives of penicillin, cephalosporin and carbapenems because they share a similarity between the side chain rather than the beta-lactam structure. Therefore, the same or closely related drug must be avoided to which the patient has shown sensitivity in the past. In certain circumstances, certain drugs are more likely to be toxic. Ampicillin and amoxicillin rash are more common when lymphoid tissue is ebullient, in the case of lymphomas or glandular fever. The following are commonly used antimicrobials for prophylaxis along with their side effects:

  • Penicillin: side effects are reactions of hypersensitivity, renal damage, low potassium (hypokalemia)
  • Cephalosporin: side effects are reactions of hypersensitivity, reduction of blood cell levels such as: neutrophils, leucocytes (leucopoenia) and thrombocytopenia, nausea and vomiting, gastrointestinal problems diarrhoea, anorexia.
  • Metronidazole: side effects are toxicity of the CNS, problems in gastrointestinal tract, neutropenia, blood clotting problems, and alcohol reactions
  • Antibiotic resistant: The bacterial resistance mechanisms are known to include genetic changes, antibiotic metabolism by bacteria, like beta lactamase (beta lactamases), altered receptor site affinity, cell wall permeability alterations (antibiotic efflux pump) and the environmental influence at infection sites. In pus, most bacteria are relatively resistant in the dormant phase. The slow cellular immune mechanism does not affect the intracellular microbes such as tubercle bacillus, Brucella abortus, and Salmonella typhi. This partly explains the slowness of antibiotics in these infections. Infections on heart valves and the meninges, for example, are more resistant to antibiotics than infections elsewhere because the concentrations of polymorphs and macrophages are low. Inappropriate antibiotic treatment facilitates the spread of resistance. In many countries, UTI-associated antibiotic resistance has become widespread. Previous studies showed an increased rate of antibiotic resistance. Antimicrobial resistance in enteric and oropharyngeal flora may be developed through the use of antibiotics for prophylaxis. A recent study has reported a high rate of resistance against third generation cephalosporins in children who received prophylactic antibiotics. Clinicians are advised to carefully use prophylactic antibiotics. Additional hazards are present in antibiotics that inhibit the growth of a range of different types of bacteria. These medications also eliminate benign bacteria that help protect us from diseases by competing with pathogenic bacteria and limiting their propagation. Wide ranging antibiotics may produce deep changes in bacterial population composition and lead to the outgrowth and invasion of so-called superinfections of antibiotic-resistant strains.

Since the V. Cholerae infection dose is high, proper hygiene generally makes immunisation and prophylaxis unnecessary, hence antimicrobial prophylaxis in endemic areas has not proved effective. In the prevention of sexually transmitted diseases, chemical prophylaxis is ineffective. The use of antimicrobials to prevent genital diseases may, indeed, deteriorate the situation by selecting harder resistant strains. Antibiotic products, especially those of a wide activity range, alter the normal flora of the body, allowing resistant and opportunistic pathogens to colonise and multiply. These could cause secondary infections in a healthy female, such as candida vaginitis, or fungal and systemic infection in a highly susceptible patient, such as an immunosuppressive treatment. Clostridium difficile, anaerobic bacterium which can multiply after normal flora is suppressed and is relatively resistant to many commonly employed antibiotics but metronidazole or vanzomycin, causes the severe complication of pseudomembraneous colitis. Between 2000 and 2007, 400 percent of the increased mortality from Clostridium difficile infection was partially due to the emergence of the insusceptible C. fluoroquinolone strain. When pseudomembraneous colitis is developed in transplant patient, it is impaired to absorb the immunosuppressive medications which increase allograft-rejection susceptibility.

Other disadvantages of prophylactic use of antimicrobials are:

  • More expensive treatment: Antibiotics are costly and shouldn’t be used inappropriately. However, the cost of the antibiotics is negligible compared to the cost of hospitalisation for a long stay due to a wound infection in patients at clearly reduced risk of wound infections which were found by prophylaxis. The least cost-effective agent for a short period of time is selected if antibiotic prophylaxis is used.
  • Allergies and toxic reactions: When antibiotics are used, toxic or allergic reactions may occur. These can be reduced for brief periods by using safe agents.
  • The use of antibiotics can lead to a false sense of safety. Careful surgery and precautionary and postoperative care are essential if wound infections are to be minimised.
  • Infection due to side effects by drugs, especially clindamycin, with bacteria such as the Clostridium difficile.

Conclusion:

The use of antimicrobial prophylaxis has led to a large number of infections being prevented and significant declines in surgical infections at the site. Specific, accepted indications should be limited to antimicrobial prophylaxis to avoid excess cost, toxicity and resistance to antimicrobials. The potential risks and benefits of any antimicrobial prophylaxis system should be understood by patients. Although there is evidence based antimicrobial prophylaxis practises, many are based on low evidence or expert advice. Additional antimicrobial prophylaxis studies are necessary. There remain significant controversies in antimicrobial prophylaxis, with many opportunities to practise improvement through rigorous studies. More antibiotics do not always reduce surgical site infection more effectively. There are significant gaps between directives and practises, mainly over the current guidelines on antibiotic prophylaxis.