Antimicrobial Resistance Overview

Antimicrobials

• Antimicrobials are chemicals toxic to microbes, but harmless to the host.
• They disrupt bacterial cell walls, inhibit unique bacterial enzymes, and disrupt bacterial protein synthesis.

Acquired Resistance to Antimicrobial Drugs

• Over time, some organisms develop resistance.
• Organisms may have been highly responsive to a drug, but then become less susceptible to it.

Antibiotic Resistance in Animals and Humans

• Animals, such as pigs, chickens, and birds, can develop resistance to antibiotics used in humans.
• Bacteria in animals can develop resistance.
• Humans can develop infections caused by resistant bacteria.
• Common antibiotic treatment plans were established between 1960 and 1970.

Antibiotic Use and Drug-Resistant Microbe Emergence

• A new infection can occur while a patient is taking medications for a different infection (suprainfection).
• The primary infection's antibiotics can eliminate the normal flora which causes an imbalance.
• A second infection can flourish due to the lack of the normal flora bacteria.
• Broad-spectrum antibiotics destroy more normal flora than narrow-spectrum antibiotics.

Suprainfection (Superinfection)

• Examples: C. difficile, thrush, and vaginal infections.

Microbial Mechanisms of Drug Resistance

• Inactivate drug
• Drug antagonist
• Alters molecule

Selection of Antibiotics

• Lab culture and sensitivity tests identify the organism and its drug sensitivity.
• Drugs may be ruled out if the patient has an allergy or liver/kidney issues.

Other Selection Rationale

• Empiric therapy is used before the causative organism is identified.
• Prophylactic agents are given to prevent infection, rather than to treat an established infection.

Monitoring of Antimicrobial Therapy

• Nurses monitor clinical responses and laboratory results.
• Look for reduction in fever and resolution of infection signs/symptoms in the affected organ/area.
• Signs should include redness, heat, swelling, pain, and drainage.

Nurse to Monitor Patient Lab Values

• Serum drug levels for toxicity (peak and trough levels)
• Renal function (BUN, creatinine)
• Hepatic function (ALT, AST)
• Infection-related values (WBC)

Patient Teaching

• Provide information about the purpose, use, specific medications, and side effects.
• Inform women of childbearing age that antibiotics can reduce the effectiveness of birth control pills.
• Advise using a second form of birth control until a new pack of pills starts.
• Check for drug-drug interactions.

Antibiotic: Types

• Drugs that weaken the cell wall include penicillins (drug name ends in "-cillin").

Penicillin (PCN) Uses and Side Effects

• Uses: syphilis, rheumatic heart disease, gas gangrene, pneumonia, respiratory infections, anthrax, septicemia, and meningitis.
• Side effects: GI distress, oral or vaginal candidiasis, generalized rash, and anaphylaxis.

Penicillins

• Active against many bacteria.
• Low direct toxicity.
• Principal adverse effect: allergic reaction.
• Bacteria take up excess water causing cell wall weakening and rupture.

Bacterial Resistance: Inactivation of Penicillins by Bacterial Enzymes

• Beta-lactamases inactivate penicillin (e.g., penicillinase).
• MRSA (methicillin-resistant Staphylococcus aureus) is a bacteria type.

Penicillin Combinations

• Extends the antimicrobial spectrum when combined with penicillinase-sensitive antibiotics.
• Examples: ampicillin/sulbactam (Unasyn), amoxicillin/clavulanic acid (Augmentin).

Penicillin Allergy

• Skin tests for penicillin allergy, and assess for penicillin allergy for each patient.
• If a patient has a history of anaphylaxis, do not administer penicillin or cephalosporins.
• Allergic to one means allergic to both.

Broad-Spectrum Penicillins

• Examples: ampicillin, amoxicillin.

Potassium penicillin G

• Least toxic and contains potassium.
• Monitor potassium levels.

Other Antibiotics That Weaken the Bacterial Cell Wall II

• Classification: Cephalosporin (e.g., Keflex)
• Classification: Glycopeptide (e.g., Vancomycin)

Cephalosporins

• Most widely used group of beta-lactam antibiotics.
• Similar to penicillin structure.
• Low toxicity.
• Watch for effects like rash, anorexia, hypersensitivity, and GI pain.

Cephalosporins: Drug Interactions

• Drugs that promote bleeding (ASA, NSAIDs, Warfarin)
• Interferes with vitamin K level causing increased anti-coagulation.
• Vitamin K causes coagulation.
• Adverse effects: allergy, bleeding, thrombophlebitis.

Glycopeptide: Vancomycin

• Action: Inhibits cell wall synthesis.
• Uses: Severe infections, methicillin-resistant Staphylococcus aureus, Clostridium difficile if metronidazole doesn't work.

Vancomycin

• Adverse effects: ototoxicity (reversible or permanent), red man syndrome (IV administration), renal toxicity.
• Avoid rapid infusion of the IV administration.

Bacteriostatic Protein Inhibitors of Synthesis

• Tetracyclines
• Macrolides

Tetracyclines

• Drug and food interaction: Absorption is decreased with milk products, calcium supplements, and most antacids (reduce the absorption of tetracycline).
• Precautions: Avoid giving to patients with kidney disease, due to tetracycline accumulating in the urine.
• Potential side effects: discoloration of teeth, diarrhea (potentially life-threatening C. Diff suprainfection), photosensitivity.

Macrolides (Erythromycin)

• Broad-spectrum antibiotic.
• Inhibits bacteria protein synthesis.
• Use if allergic to penicillin.
• Adverse effects include gastrointestinal issues, dysrhythmias, and superinfection.

Bactericidal Inhibitors of Protein Synthesis: Aminoglycosides

• Bactericidal (kills bacteria).

Aminoglycosides

• Commonly used: gentamicin, tobramycin, amikacin.
• Adverse effects (peak and trough levels): nephrotoxicity, ototoxicity, hypersensitivity reactions, neuromuscular blockade, and blood dyscrasias.
• Excreted unchanged in the urine (80–90% recoverable).

Sulfonamides

• Inhibits synthesis of folic acid (bacteria need folic acid to replicate).
• Primary use: urinary tract infections.
• Adverse effects: rash, hypersensitivity reactions (Stevens-Johnson syndrome), mortality rate of 25%. Blisters will be present on mucous membranes and skin.

Trimethoprim

• Suppresses bacterial DNA synthesis.
• Combined with sulfonamides.
• Uses: urinary tract infections.

Trimethoprim-Sulfamethoxazole (TMP-SMZ)

• Combination of trimethoprim and sulfamethoxazole.
• Trade names: Bactrim and Septra.
• Inhibits sequential steps in bacterial folic acid synthesis.
• Primary use: urinary tract infections.

Antibacterial Drugs: Fluoroquinolone and Metronidazole

Fluoroquinolones

• Disrupts DNA replication and cell division.
• Side effects: tendon rupture (Black Box Warning for prescribers).
• Usually affects Achilles tendon; inflammation or rupture possible.

Fluoroquinolones: Ciprofloxacin (Cipro)

• Drug of choice for anthrax.
• Used to treat respiratory, urinary tract (UTI), gastrointestinal (GI) infections, bone, joint, skin, and soft tissue infections.
• Adverse effects include GI (mild; nausea, vomiting, diarrhea, abdominal pain), central nervous system (CNS) issues (dizziness, headache, restlessness, confusion, seizures), and confusion, lethargy, and visual issues in older adult patients.

Fluoroquinolones: Drug and food interactions

• Absorption may be reduced with aluminum, magnesium antacids, iron salts, zinc salts, sucralfate, and milk/dairy products.

Metronidazole (Flagyl)

• Inhibits nucleic synthesis (DNA/RNA)
• Used to treat Clostridium Difficile (C. Diff).
• C. Diff Treatment: stop the precipitating antibiotic, hand sanitizers are ineffective, do not give anti-diarrheal drugs.

This quiz explores the nature of antimicrobials, their toxic effects on microbes, and the evolution of resistance in both humans and animals. It highlights the implications of antibiotic use and the emergence of drug-resistant microbes, detailing how resistant infections can occur. Test your knowledge on these crucial topics in microbiology and pharmacology.