Prolonged antibiotic use refers to the administration of antibiotic medication for a longer-than-usual period of time, set by some authors as 1 month. Antibiotics are drugs that are used in the treatment or prevention of bacterial infections. In complicated infections, such as those affecting more organs of the body, involving more species of bacteria or resistant ones, or not responding to initial treatment, the treatment with antibiotic drugs may need to continue for a longer time period. An important quality for an antimicrobial drug is selective toxicity, meaning that it selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host. However, prolonged administration of antibiotics can lead to several adverse effects, some of which can negatively affect fertility.
Candidiasis
The yeasts of Candida genus live on the skin and mucous membranes of healthy individuals, but do not cause any health problems due to present bacterial microflora. When the healthy bacterial microflora is reduced, the candida takes over and grows on mucous membranes, such as the oral cavity, tongue and vagina. The overgrowth of candida then causes a group of infections known as candidiasis. In the oral cavity, candidiasis is known as thrush (Pic. 1). In the vagina and on the vulva, candida infection causes vulvovaginal candidiasis. In males, candida may cause infection of the head of the penis, called candida balanitis or balanitis thrush.
In general, candida infections have excellent prognosis if treated, and do not significantly affect fertility. If a woman experiences vulvovaginal candidiasis, which responds to treatment, once or twice a year, it will probably not affect her fertility in any way, except the discomfort caused by its symptoms. However, if the candidiasis is more frequent, it can be a sign of imbalanced vaginal microflora, or it can directly lead to changes in the vaginal flora itself. This can cause changes in the cervical mucus, which make it more difficult for sperm to reach the uterus. Also, changes in the vaginal microflora make the vagina more susceptible to other infections, including sexually-transmitted diseases, which can impair fertility in the future.
Non-obstructive azoospermia
Studies show that while most commonly used antibiotic do not interfere with female reproductive system, many commonly used antibiotics can have negative effects on spermatogenesis (sperm cell production). Such antibiotics include ampicilin, tetracycline, nitrofurantoin, aminoglycosides and some macrolides, such as erythromycin. Long-term treatment with these antibiotics can lead to lower sperm production and lower sperm viability. Eventually, this adverse effect can lead even to non-obstructive azoospermia (Pic. 2) due to testicular failure to produce sperm. However, adverse effects on male fertility are uncommon, and they usually subside after finishing the therapy.
Symptoms
Prolonged antibiotic treatment is commonly associated with some of of mild adverse effects of antibiotics. These include rash, dyspepsia (upset stomach), nausea, vomiting and diarrhea. Elevated liver enzymes are also common. Specific groups of antibiotics may then produce other adverse effects that are specific to their group. More symptoms may be present if the antibiotic treatment causes one of the complications mentioned above.
Associated diseases
Bacterial infections
Antibiotic treatment is the basis of bacterial infections treatment. Effective antibiotic treatment regimens consist primarily of two variables: the dose and the duration of treatment. The duration of the treatment may depend on the site of infection, the causative bacteria and the response of the patient. Infections in sites with poor penetration of antibiotics may require a longer course of antibiotic treatment to be cured. Complicated infections, such as sepsis, and patients that respond poorly to initial antibiotic treatment may also require longer treatment duration, which increases the risk of associated complications.
Complications
Antibiotic resistance
Excessive and inappropriate use of antibiotics is highly associated with the emergence of antibiotic resistance (Pic. 3). Antibiotic resistance is now recognized as one of the most serious threats to human health, spreading across national boundaries. It is the result of selection of drug-resistant strains in clinical environments, the overuse and misuse of antibacterials, the use of sub-therapeutic doses (doses lower than needed for a therapeutic effect) of antibacterial drugs, and poor patient compliance with antibacterial drug therapies.
Microbiome alteration
Long-term use of antibiotics is associated with changes of the microbiome. The normal microbiome constitutes bacterial populations that live inside the human body, mostly in the digestive system and on mucous membranes. This bacterial colonization is normally mutually beneficial and does not cause bacterial infections of the host. However, long-term antibiotic use can eliminate most of these „healthy“ bacteria and allow for more resistant bacterial strains to thrive, which may then cause severe bacterial infections. Such a bacteria is the Clostridium difficile (Pic. 4) commonly seen in people using broad spectrum antibiotics or undergoing long-term antibiotic treatment. This bacterium grows in the intestines of such patients and can cause very severe disease called pseudomembranous colitis, an ulcerative inflammation of the intestine wall.
Candidiasis
The yeast candida is normally present on the skin and mucous membranes. In condition of immunodeficiency (impaired immunity) or decline of the normal bacterial microflora, its overgrowth leads to so-called opportunistic candida infections, or candidiasis. Superficial candidiasis, affecting only the surface of the skin or the mucous membranes, is more common than candidiasis affecting internal body organs. The most common forms of superficial candidiasis are oral candidiasis (thrush), candida vulvovaginitis in females, and candida balanitis (infection of the head of the penis) in males. Infection of the vagina or vulva may cause severe itching, burning, soreness, irritation, and a whitish or whitish-gray cottage cheese-like discharge. Symptoms of infection of the male genitalia (balanitis thrush) include red skin around the head of the penis, swelling, irritation, itchiness and soreness of the head of the penis, thick, lumpy discharge under the foreskin, unpleasant odour, difficulty retracting the foreskin (phimosis), and pain when passing urine or during sex.
Risk factors
Prevention
There is currently little evidence of adverse effects of prolonged antibiotic therapy on female fertility and the ability of a woman to conceive.
However, several commonly used antibiotics have been shown to negatively affect fertility in males. Antibiotics such as tetracycline, aminoglycosides, nitrofurantoin or macrolides, such as erythromycin, may lower sperm count and impair sperm viability and motility. In males that have been treated with these antibiotics for a longer period of time, sperm counts may be significantly lower or a large percentage of the sperm may be non-viable. If the testicles fail to produce sperm cells completely, the condition is termed non-obstructive azoospermia.
With proper administration and dosage, most antibiotics are safe with relatively few adverse effects. Common adverse effects are usually mild and short-lived. If long-term adverse effects appear, they usually subside after finishing the antibiotic treatment. Adverse effects affecting fertility are not very common and they resolve soon after the therapy has been completed.
