Chemoprophylaxis: What is it? Examples, Adverse Effects, Uses and Duration

Travelers to tropical countries are always at risk for various infectious diseases.

In some cases, there are effective vaccines, but chemoprophylaxis can be offered for other infections.

The prevention of malaria has become increasingly complex as the Plasmodium species become resistant to the available drugs. In specific high-risk settings, antibiotics can be used to prevent leptospirosis, typhus, and other infections.

Post-exposure prophylaxis is appropriate for selected virulent infections. In this article, the tests for chemoprophylaxis will be reviewed.

Chemoprevention (also chemoprophylaxis) refers to administering a drug or several drugs to prevent the development of a disease or infection.

Antibiotics, for example, can be administered to patients with disorders of the immune system function to prevent bacterial infections (particularly opportunistic infections).

Antibiotics may also be given to healthy people to limit the spread of an epidemic or to patients who have repeated infections (such as urinary tract infections) to prevent a recurrence.

 

It can also refer to heparin administration to prevent deep vein thrombosis in hospitalized patients.

In some cases, chemoprophylaxis is initiated to prevent the spread of an existing infection in an individual to a new organ system, such as when intrathecal chemotherapy is administered in cancer patients to prevent further disease.

Chemoprophylactic agents are based on knowledge of the epidemiology and clinical implications of the infectious diseases for which protection is sought. Generally, chemoprophylaxis is taken for illnesses that are common or where the clinical impact of the infection is high.

Medications may be taken before exposure (pre-exposure prophylaxis) or after possible exposure to an infectious agent (post-exposure prophylaxis).

In addition to the severity and frequency of the disease, the tolerability, toxicity, and ecological implications of the medications used are essential in determining whether drugs are prescribed and taken. Vaccines are the most effective and safest way to prevent infection in many cases.

Passive immunotherapy is also used to prevent infection before or after exposure to infectious agents.

The chemoprophylaxis of infection in children can be classified as general or specific.

Generally, all children, regardless of underlying disease or other factors, have a substantial risk of infection after exposure to a pathogen, and an antimicrobial agent can prevent the disease (e.g., Neisseria meningitides in households).

Specific chemoprophylaxis is given to confident children at particular risk of infection due to an immunoreactive state or anatomical structural abnormalities.

It must be administered during the entire interval of the documented increase in the risk of infection. The duration of general or specific chemoprophylaxis varies.

Chemoprophylaxis eradicates nasopharyngeal transport and prevents secondary cases in close contact. Chemoprophylaxis consists of rifampin twice a day for four doses or a single dose of ciprofloxacin. Ceftriaxone as a single intramuscular dose may also be offered.

Azithromycin has also shown efficacy among children, but it is not recommended routinely. Knowing that the rate of attack among households or other close contacts of meningococcal cases is more than 400 times higher than the general population, chemoprophylaxis should be offered for people at risk.

Close contacts include those living in the same home, contacts in daycare centers, and anyone directly exposed to the patient’s oral secretions with meningococcal disease. Prophylaxis is not indicated if the exposure to the index case was brief.

Chemoprophylaxis should be administered as soon as the index case is identified and up to 7 days after exposure; after 14 days, chemoprophylaxis is ineffective.

Since treatment with penicillin alone is not reliable for eradicating nasopharyngeal transport, terminal prophylaxis should be administered to patients at hospital discharge.

Vaccination instead of chemoprophylaxis is usually offered during outbreaks in large populations due to the cost of chemoprophylaxis and the increased likelihood of resistance to antimicrobials.

Chemoprophylaxis should also be considered in patients with latent infection before the start of tumor necrosis factor inhibitors, and all these patients should be screened.

The use of chemoprophylaxis in possible transplant recipients is established. Chemoprophylaxis should be deferred in pregnant women, a group more prone to isoniazid hepatitis.

The use of chemoprophylaxis is limited mainly by two factors: risk and financial costs.

  • All medications have the potential to cause side effects. In general, chemoprophylaxis should be initiated only when the benefits of treatment outweigh the risks.
  • The cost associated with chemoprophylaxis can be prohibitive, mainly when the cost of treatment is high, or the incidence of the target disease is low. Many forms of chemoprophylaxis are not profitable.

Examples of effective chemoprophylaxis:

A manifestation of the abuse of antibiotics is that between 30% and 50% of the time, the antibiotic is prescribed to prevent an infection instead of treating it.

Penicillin G prevents infection by group A streptococci.

Intermittent use of trimethoprim-sulfamethoxazole prevents recurrent urinary tract infections.

Prevention of endocarditis in patients with cardiac valvular injuries that will undergo a surgical procedure.

The most extensive use of chemoprophylaxis in preventing wound infections after surgery.

 Uses in specific diseases

The use of chemoprophylaxis as a treatment against the early signs of tuberculosis has proven its effectiveness. In familial adenomatous polyposis, doctors observed the regression of polyps with non-steroidal anti-inflammatory drugs for anti-inflammatory therapy.

Chemoprophylaxis is also used to treat meningococcal infections through close contact with Neisseria meningitides.

Streptococcal infection:

The chemoprophylaxis of streptococcal infection with phenoxymethylpenicillin is necessary for patients who have had an attack of rheumatic fever. Continue for at least five years or until you are 20 years old, whichever is the most extended period (although some argue that it should continue for life).

Chemoprophylaxis should continue for life after the second attack of rheumatic fever. A single episode of acute nephritis is not an indication of chemoprophylaxis. Ideally, chemoprophylaxis should continue throughout the year but cover at least the coldest months if the patient is not willing to undergo this.

Tuberculosis

Chemoprophylaxis is an increasingly important component of tuberculosis control programs. The combined effect of disease treatment and infection is synergistic at the population level.

Prophylaxis is already recommended for all contacts under five years of age with tuberculosis cases once they have been eliminated from having tuberculosis.

Prophylaxis is practiced more frequently and successfully in tuberculosis control programs in higher-income countries.

Isoniazid for nine months is the most commonly used. More and more alternative regimens shorter than 3 or 4 months are used with at least equivalent efficacy, better adherence, and acceptable side effects profiles.

Chemoprophylaxis is recommended in patients seropositive to HIV due to the higher incidence of clinical disease in patients exposed to mycobacterial tuberculosis and in endemic areas of tuberculosis, regardless of the results of the infection tests.

Cancer

Chemoprevention of cancer involves the administration of substances that block or compensate for the last stages of carcinogenesis. At least three groups of substances have demonstrated chemopreventive activity in humans:

Hormonal agents: Selective estrogen receptor modulators, including tamoxifen and raloxifene, and aromatase inhibitors, including anastrozole, letrozole, and exemestane, can prevent breast cancer.

Retinoids: can prevent cancer of the upper respiratory tract in smokers.

Nonsteroidal anti-inflammatory drugs: can prevent death from cancer of the large intestine and breast.

There is still no evidence that chemoprevention reduces cancer-related morbidity and mortality. Of particular concern is the case of finasteride, which reduced the overall incidence of prostate cancer but seemed to increase the risk of more aggressive forms of the disease.

Mycotic infection

As invasive fungal infection remains a common problem in treating patients with cancer, the chemoprophylaxis of these opportunistic infections is desperately needed.

The most frequently investigated antifungal agents have been nystatin, amphotericin B, and ketoconazole.

In placebo-controlled studies, high doses of antifungal agents decreased positive results from surveillance cultures. There are some suggestions that such chemoprophylaxis may reduce the incidence of invasive candidiasis in patients with neutropenic cancer.

However, no oral chemoprophylaxis has effectively prevented aspergillosis or mucormycosis in these patients. There are still many areas of controversy, and the most appropriate regimes have not yet been defined.

Zoonosis

It was found that chemoprophylaxis with doxycycline in soldiers visiting endemic areas significantly reduces the number of cases of leptospirosis.

In a randomized controlled trial, doxycycline prophylaxis did not reduce leptospira rates but significantly prevented morbidity and mortality during outbreaks.

Chemoprophylaxis with doxycycline, either 200 mg weekly or a short cycle for three days, is recommended to control outbreaks or travelers, although data are limited. It has been shown that penicillin G is of little use.

Empiric treatment with doxycycline has the additional benefit of covering other infections such as rickettsial infections.

Haemophilus influenzae (Hib) disease

Chemoprophylaxis is recommended for close contact with patients with invasive Hib disease who live in a home with a child under four years of age and have not received an adequate number of vaccines against Haemophilus influenzae (Hib) according to age or who are immunosuppressed.

Prophylaxis is also recommended for child care and preschool contacts when vaccinated, or unvaccinated children attend the facility. There have been at least two cases of invasive Hib disease among attendees within 60 days.

Chemoprophylaxis should be started as soon as possible. Rifampin is the drug of choice for prevention. The regime is as follows:

  • Oral Rifampicin Adults 600mg, once a day for four days. Children 20mg / kg, once a day for 4 days.

Chemoprophylaxis is not recommended for close contact with cases of pneumococcal meningitis.

The common cold

Chemoprophylaxis or immunoprophylaxis is generally not available for the common cold. Influenza immunization or chemoprophylaxis may help prevent colds caused by this pathogen, but influenza is responsible for only a tiny proportion of all colds.

Vitamin C, even in megadoses, is not beneficial. Other non-pharmacological interventions promoted as an effective prevention for the common cold but unproven benefits include zinc, vitamin E, echinacea, ginseng, probiotics, exercise, and hand washing.

Handwashing and exercise have undeniable benefits for general health and can be recommended despite lacking specific evidence preventing the common cold.

Other interventions, although probably safe, have no demonstrable benefit and contribute to unnecessary medical care expenses related to the common cold.

Risk of malarial infection

One of the most challenging questions in malaria prophylaxis today is how to advise travelers who visit low-risk areas, which are often areas with unstable transmission and changing epidemiology of malaria.

Few studies reported absolute risk in specific areas. Still, these data are necessary to allow a rational decision on whether or not to recommend chemoprophylaxis against the risk of side effects.

Travelers should not be exposed to a substantial risk of adverse events from chemoprophylaxis of malaria in areas where malaria infection is very low.

Leptospirosis

The frequency and intensity of extreme weather events, hefty rains, and floods are expected to increase, likely increasing the risk of leptospirosis outbreaks.

In a systematic review of the published literature on massive chemoprophylaxis to reduce the health impact of leptospirosis, we found that oral doxycycline was the most widely used antibiotic.

Although the evidence for the effectiveness of post-exposure prophylaxis in the literature is inconclusive, the direction of association observed supported a protective effect for morbidity and mortality.

However, additional research is needed to understand the direct benefit of chemoprophylaxis in leptospirosis infection and disease and identify the factors influencing the benefits and risks in different settings.

Indications of post-exposure chemoprophylaxis

Clinical judgment and advice from local authorities are essential factors in making decisions about chemoprophylaxis after exposure.

In areas with limited availability of antiviral drugs, local public health authorities may provide additional guidance on prioritizing chemoprophylaxis within groups at higher risk of complications.

In certain situations, local public health authorities may recommend that antiviral drug resources be directed primarily to treatment and that antiviral chemoprophylaxis be used only in certain limited cases.

Chemoprophylaxis with antiviral drugs is not a substitute for the influenza vaccine when the influenza vaccine is available.

Adverse events associated with antiviral medications are usually mild and self-limiting. Still, they may result in morbidity resulting from the side effects of drugs that outweigh the potential benefit of antiviral chemoprophylaxis.

In addition, the indiscriminate use of chemoprophylaxis could promote resistance to antiviral drugs or reduce the availability of antiviral medications for the treatment of people at higher risk of complications of influenza or who are seriously ill.

Patients who received post-exposure chemoprophylaxis should be informed that chemoprophylaxis decreases, but does not eliminate the risk of influenza, that the susceptibility to returning influenza once the antiviral medication stops, and that influenza vaccination is recommended if available.

Patients who received chemoprophylaxis should be encouraged to seek medical evaluation as soon as a febrile respiratory illness suggestive of influenza appears because influenza virus infection can still occur while on chemoprophylaxis.

It could also indicate infection with a virus-resistant to the antiviral medication used.

Duration of chemoprophylaxis

Post-exposure chemoprophylaxis is usually given for no more than ten days after the most recent known exposure to a close contact who is known to have influenza.

The likelihood of compliance and adverse events should be considered when determining the timing and duration of administration of influenza antiviral drugs for chemoprophylaxis.

Failure to complete an oseltamivir course for chemoprophylaxis due to gastrointestinal adverse events is common and can lead to antiviral resistance.

The duration of chemoprophylaxis before exposure based on a potential vulnerability in the community depends on the time of community influenza activity.

Regimens of up to 28 days for zanamivir and 42 days for oseltamivir have been tolerated, but no published data on the use of regimens lasting> 6 weeks are available.

To be as effective as chemoprophylaxis before exposure, the medication must be taken every day for the duration of influenza activity in the community.

During periods of widespread community activity and availability of limited or no influenza vaccines, such as during the 2009 H1N1 flu pandemic.

Chemoprophylaxis before exposure plays a minimal role due to concerns about the supply of antiviral drugs, the need for long-term use and the possibility of adverse events, and the selection of antiviral resistance.

Preventing infection with an antiinfective is theoretically possible for any condition with satisfactory treatment. Pre-exposure prophylaxis is effective when the risk of acquiring an infection is high, and the drugs used to prevent disease are well tolerated and easy to take.

This is generally the case of the prophylaxis against malaria that travelers take. Chemoprophylaxis for other tropical infections is not as well established but should be considered for travelers who plan to be exposed to a higher level of risk.

Post-exposure prophylaxis is provided after an unforeseen exposure to infectious agents that can have serious consequences. In this situation, pharmacological regimens do not necessarily have to be as convenient or well-tolerated as drugs are taken for pre-exposure prophylaxis.

In many cases, chemoprophylaxis should have a secondary role in other non-pharmacological measures known to reduce infection risk.

Adverse effects

They are usually uncommon.

Patients who take prophylaxis with penicillin may have penicillin-resistant viridans-type streptococci in the mouth, so even during minor dentistry, there is a risk of bacteremia and, therefore, of infectious endocarditis with a penicillin-resistant organism in those with rheumatic injury.

Patients who take penicillins are also carriers of staphylococci and resistant pneumococci.