Mechanisms of action and clinical adverse effects of major antibiotics

Antibiotics

Penicillin

Mechanism of Action

Penicillin G, when injected into the patient, will act against actively proliferating penicillin-sensitive strains of bacteria (Drugs.com, 2011). This does not include several strains of staphylococci producing penicillinase or bacteria that are quiescent. The mechanism of action is inhibition of cell-wall mucopeptide biosynthesis. Penicillin G. works best against staphylococci groups A, B, C, G, H, L, and M, pneumococci, Neisseria meningitides, Neisseria gonorrhoeae, Treponemapallidum, and many others.

Clinical Uses

Penicillin is used to treat serious infections, such as septicemia, pneumonia, endocarditis, pericarditis, empyema, and meningitis (Drugs.com, 2011). Penicillin is also indicated in cases of anthrax, botulism, actinomycosis, diphtheria, listeria infections, erysipelothrix endocarditis, severe infections of the oropharynx, lower respiratory tract, and genitals. Penicillin is also used to treat gonorrhea, syphyilis, rat-bite fever, and Haverhill fever. Only penicillin-sensitive bacteria should be treated due to the risk of creating penicillin-resistant strains. Although treatment should begin immediately in urgent cases, the sensitivity of the infectious agent should be determined in all cases to prevent the development of drug-resistant strains.

Adverse Effects

Penicillin should be used cautiously in individuals with a history of allergic disease and should an allergic reaction occur, it use should be discontinued, unless penicillin is the only viable treatment for a life-threatening condition (Drugs.com, 2011). The estimated prevalence of penicillin allergy is between 0.7 to 10%. In patients with syphilis or other spirochetal infections, the following may occur within two hours and resolve within 24 hours: fever, chills, myalgias, headaches, tachycardia, hyperventilation, and vasodilation. This may be due to the release of pyrogens into the system. Gastrointestinal distress can occur: nausea, vomiting, stomatitis, and black or hairy tongue. High doses in renal patients can cause hemolytic anemia, serious or fatal electrolyte imbalances (due to sodium content), congestive heart failure, kidney damage, seizures, and coma.

Gentamicin

Mechanism of Action

Gentamicin belongs to a class of antibiotics defined by an aminoglycoside group (Drugs.com, 2014a). Gentamicin is harvested from the Micromonospora purpurea cultures. The bactericidal activity of gentamicin depends on the binding of the aminoglycoside group to bacterial ribosomes, thereby inhibiting translation. Gentamicin is active against both Gram-positive and -negative organisms.

Clinical Uses

As with most antibiotics, the use of gentamicin should be based on culture results and local epidemiological data to minimize the emergence of drug-resistant strains (Drugs.com, 2014a). Gentamicin is effective against sensitive strains of Pseudomonas aeruginosa, indole-positive and -negative strains of Proteus species, Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species, and coagulase-positive and -negative Staphylococcus species. Common uses include serious cases of neonatal sepsis, meningitis, and infections of the urinary, respiratory, and gastrointestinal tracts.

Adverse Effects

Given Gentamicin's toxicity, its use in initial urinary tract infections is not recommended unless the organism is resistant to less toxic antibiotics and susceptible to gentamicin (Drugs.com, 2014a). The organs affected by gentamicin toxicity include kidneys and the nervous system. Neurotoxicity is most common in patients with impaired renal function and can lead to the development of dizziness, vertigo, tinnitus, irreversible hearing loss, and other auditory problems. Peripheral neurotoxicity can cause numbness, tingling, twitching, convulsions, and Myasthenia gravis-like symptoms.

Azithromycin

Mechanism of Action

The bactericidal activity of azithromycin results from binding to prokaryotic 23S ribosomal RNA, thereby inhibiting assembly of the 50S ribosomal unit and subsequent translation (Drugs.com, 2014b). The distribution of the drug to sites of infection may be mediated by the accumulation within phagocytes, at levels 30-times higher than in serum.

Clinical Uses

Azithromycin is recommended for routine treatment of adult airway infections, including patients suffering from community-acquired pneumonia and chronic obstructive pulmonary disease (Drugs.com, 2014b). Azithromycin treatment is contraindicated in patients with hospital-acquired pneumonia, cystic fibrosis, bacteremia, or who require hospitalization. Other uses include treatment of uncomplicated skin infections, urethritis, cervicitis, and genital ulcers. Similar uses are recommended for pediatric patients.

Adverse Effects

The most common adverse effect of azithromycin treatment is caused by multiple-dose regimens, which can lead to the development of gastrointestinal symptoms, including nausea, vomiting, diarrhea, and stomach pain (Drugs.com, 2014b). Rare side effects (< 1%) include heart palpitations, chest pain, dizziness, vertigo, headache, fatigue, rash, and photosensitivity.

Doxycycline

Mechanism of Action

The bactericidal activity of doxycycline depends on binding to the prokaryotic 30S ribosomal subunit, thereby inhibiting translation (Drugs.com, 2014c). Doxycycline has been proven effective against a wide range of Gram-positive and -negative bacteria.

Clinical Uses

Doxycycline, a tetracycline, is used to treat a large number of infections (Drugs.com, 2014c). The list of applications include typhus, Rocky Mountain spotted fever, tick fevers caused by Rickettsiae, plague, cholera, upper respiratory tract infections, anthrax, sexually-transmitted diseases, severe acne, and as an adjunct treatment with amebicides. Each use depends on the identity of the responsible organism and whether culture or epidemiological data is consistent with doxycycline sensitivity.

Adverse Effects

Doxycline is completely absorbed in the intestines, so gastrointestinal problems are rare (Drugs.com, 2014c). Tetracyclines in general can cause skin reactions, renal problems, allergic reaction, hemolytic anemia, thrombocytopenia, neutropenia, eosinophilia, and intracranial hypertension.

Co-Trimoxazole

Mechanism of Action

A brand-name co-trimozazole, Septra, contains 80 mg of trimethoprim and 400 mg of sulfamethoxazole in a single tablet (Drugs.com, 2013). The bactericidal activity of Septra is due to the blocking of the folate biochemical cycle, which is essential for the production of prokaryotic proteins and nucleic acids. Trimethoprim binds to and inhibits dihydrofolate reductase, while sulfamethoxazole inhibits dihydrofolic acid synthesis by competing with para-aminobenzoic acid.

Clinical Uses

The most common clinical uses for Septra are urinary tract infections, acute otitis media, acute exacerbations of adult chronic bronchitis, adult traveler's diarrhea, shigellosis, and pneumonia due to Pneumocystis carinii. The clinical use of Septra to treat these infections depends on the bacterial species responsible and whether it is susceptible to trimethoprim and sulfonamides.

Adverse Effects

Since administration of sulfonamides can cause fatalities due to severe reactions, co-trimoxazole use should be discontinued at the first sign of a rash, sore throat, fever, arthralgia, pallor, purpura, jaundice, cough, dyspnea, and pulmonary infiltrates (Drugs.com, 2013). Another risk associated with any antibiotic is Clostridium difficile-associated diarrhea, which results when the intestinal flora is depleted and C. difficile takes over, leading to the development of mild to fatal forms of diarrhea. The most common adverse effect is gastrointestinal distress, but Septra can also cause anemia, renal failure, hyperkalemia, hyponatremia, neurological symptoms, psychological symptoms, endocrine abnormalities, arthralgia, myalgia, respiratory problems, and fatigue.