Penicillin: Discovery, Use, and Resistance

Penicillin

• A natural antibacterial agent derived from the mold genus Penicillium.
• Introduced to the military during World War II and saved soldiers' lives.
• Became widely used in 1945, seen as a "miracle drug."
• It can be bacteriostatic or bactericidal, depending on the drug and dosage.
• Penicillin G is primarily bactericidal.
• Beta-lactam antibiotics are the main type.
• Bacteria produce betalactamases to inactivate penicillin and other beta-lactam antibiotics.
• Penicillinases are betalactamases attacking penicillins.
• Initially used for staphylococcal infections, mutant strains developed resistance due to penicillinase.
• Food doesn't significantly alter Penicillin V absorption, so it should be taken after meals, unlike amoxicillin.
• Penicillin G was the first penicillin given orally and by injection.
• Oral administration absorbs one-third of the dose.
• IV and IM routes are more effective for achieving a therapeutic serum penicillin level.
• Aqueous penicillin G has a short duration of action, and IM injection is painful.
• Procaine penicillin (milky color) was created to extend the drug's activity, with procaine to decrease injection pain.
• Penicillin V was the next penicillin produced, with two-thirds of the dose absorbed by the GI tract.
• Penicillin V is less potent than Penicillin G but effective against mild to moderate infections, including anthrax.

Basic Penicillins

• Penicillin G procaine
• Penicillin G Benzathine
• Penicillin G Sodium
• Penicillin VK

Broad-Spectrum Penicillins (Aminopenicillins)

• Used to treat both gram-positive and gram-negative bacteria.
• Not as broadly effective against all microorganisms as they once were.
• More expensive than penicillin, so should not be used when ordinary penicillins are effective.

Generic Names for Broad-Spectrum Penicillins

• Amoxicillin
• Amoxicillin clavulanate
• Ampicillin
• Ampicillin Sulbactam
• Effective against some gram-negative organisms like E. coli and Salmonella species.
• Not penicillinase resistant, so ineffective against S. aureus.
• Ampicillin and amoxicillin are examples, with amoxicillin being the most prescribed for adults and children.

Penicillinase-Resistant Penicillins (Antistaphylococcal Penicillins)

• Treat penicillinase-producing S. aureus.
• Dicloxacillin is an oral preparation, while nafcillin and oxacillin are IM and IV preparations.
• Not effective against gram-negative organisms and less effective than Penicillin G against gram-positive organisms.

Generic Names for Penicillinase-Resistant Penicillins

• Dicloxacin Sodium
• Nafcillin
• Oxacillin Sodium

Beta-Lactamase Inhibitors

• Beta-lactamase inhibitors extends a broad-spectrum antibiotic's antimicrobial effect
• Clavulanic acid, sulbactam, and tazobactam are examples of beta-lactamase inhibitors
• These inhibitors are not given alone, but are combined with a penicillinase-sensitive penicillin such as amoxicillin, ampicillin, or piperacillin.
• Drug combinations include amoxicillin/clavulanic acid (oral), ampicillin/sulbactam and piperacillin/tazobactam (parenteral).

Extended-Spectrum Penicillins (Antipseudomonal Penicillins)

• Effective against P. aeruginosa and other gram-negative organisms
• Also useful against Proteus, Serratia, Enterobacter, Acinetobacter species, and Klebsiella pneumoniae.
• Antipseudomonal penicillins are not penicillinase resistant.
• Pharmacologic action is similar to aminoglycosides, but less toxic.

Generic Names for Extended-Spectrum Penicillins

• Piperacillin Tazobactam

Pharmacokinetics of Penicillin

• Amoxicillin is well absorbed from the GI tract, while dicloxacillin is only partially absorbed.
• Amoxicillin is 20% protein bound, dicloxacillin is 95% protein bound.
• Both drugs have short half-lives.
• Amoxicillin is 60% excreted in the urine, dicloxacillin in bile and urine.

Pharmacodynamics of Penicillin

• Both amoxicillin and dicloxacillin are penicillin derivatives and bactericidal.
• The drugs interfere with bacterial cell wall synthesis, causing cell lysis.
• Clavulanic acid can be added to amoxicillin to intensify the effect by preventing breakdown by antibacterial drugs.
• Probenecid taken with either amoxicillin or dicloxacillin, may increase levels in serum
• Erythromycin and tetracycline may decrease the effects of amoxicillin
• The onset of action as well as time of peak serum concentrations are very similar for these drugs

Uses of Penicillin

• Penicillins are used to treat otitis media, pneumonia, meningitis, UTIs, and syphilis.
• Penicillins may be as a prophylactic antibiotic before surgery or dental procedures in patients with histories of rheumatic fever.

Therapeutic Outcome of Penicillin

• Elimination of bacterial infection

Common Adverse Effects of Penicillin

• Penicillins cause diarrhea by altering the bacterial flora of the GI tract

Severe Adverse Effects of Penicillin

• Transient elevations of liver function test results (e.g., AST, ALT, alkaline phosphatase levels)
• Transient elevations of renal test results (e.g., BUN, serum creatinine levels). Findings such as proteinuria, hematuria, and decreased creatinine clearance warrant attention
• content of the antibiotics may cause hyperkalemia or hypernatremia, can lead to Electrolyte imbalance
• Carefully assess thrombophlebitis in patients receiving IV penicillins

Drug Interactions of Penicillin

• Patients receiving probenecid combined with penicillins are more susceptible to toxicity because probenecid inhibits renal excretion of the penicillins. Closely monitor for adverse effects
• Concurrent use with allopurinol increases rash incidence. Verification beyond a documented allergy is needed for confirmation
• Excessive use of antacids may diminish the absorption of oral penicillins
• Penicillins may interfere with the activity of oral contraceptives. Use of additional methods of contraception should be planned.

Nursing Assessment for Penicillin Administration

• Assess for allergy to penicillin or cephalosporins.
• Evaluate lab results such as liver enzymes.
• Report elevated alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).
• Record urine output.
• Noncompliance with drug regimen related to decreased finances
• Nutrition, Imbalanced, related to nausea and vomiting

Nursing Interventions for Penicillin Administration

• The patient's infection will be controlled and eliminated.
• Obtain a sample (e.g., swab, blood, sputum) for laboratory culture and antibiotic sensitivity testing (C&S test) to discern the infective organism before antibiotic therapy is started.
• Monitor for signs and symptoms of superinfection, especially in patients taking high doses of an antibiotic for a prolonged time. Signs and symptoms include stomatitis (mouth ulcers), genital discharge (vaginitis), and anal or genital itching.

Collaborative Care for Penicillin Administration

• Examine the patient for allergic reaction to the penicillin product, especially after the first and second doses.
• This may be a mild reaction, such as a rash, or a severe reaction, such as respiratory distress or anaphylaxis.
• Have epinephrine available to counteract a severeallergic reaction.
• Do not mix aminoglycosides with a high-dose or extended-spectrum penicillin G because this combination may inactivate the aminoglycoside.

Patient Teaching for Penicillin Administration

• Teach patients to always take the entire prescribed penicillin product, such as amoxicillin, until the bottle is empty.

Cephalosporins

• In 1948, a fungus called Emericellopsis minimum (Cephalosporium acremonium) was discovered in seawater at a sewer outlet off the coast of Sardinia
• This fungus was found to be active against gram-positive and gram-negative bacteria and resistant to beta-lactamase, an enzyme that acts against the beta-lactam structure of penicillin.
• In the early 1960s, cephalosporins were used with clinical effectiveness. For cephalosporins to be effective against numerous organisms, their molecules were chemically altered, and semisynthetic cephalosporins were produced.
• Like penicillin, the cephalosporins have a beta-lactam structure and act by inhibiting the bacterial enzyme necessary for cell-wall synthesis. Lysis to the cell occurs, and the bacterial cell dies.

First-, Second-, Third-, Fourth-, and Fifth-Generation Cephalosporins

• Cephalosporins are a major antibiotic group used in hospitals and in health care offices.
• These drugs are bactericidal with actions similar to penicillin. For antibacterial activity, the beta-lactam ring of cephalosporins is necessary
• Five groups of cephalosporins have been developed, identified as generations. Each generation is effective against a broader spectrum of bacteria, an increased resistance to destruction by betalactamases, and an increased ability to reach cerebrospinal fluid

First-generation cephalosporins

• are effective against most gram-positive bacteria and are destroyed by beta-lactamases, but not all second generation cephalosporins are affected by betalactamases
• First Generation Cephalosporins
  • Cefazolin Sodium
  • Cefadroxil
  • Cephalexin (oral)

Second-generation cephalosporins

• are effective against gram-positive and some gramnegative bacteria
  • Cefrozil monohydrate
  • Cefaclor (oral)
  • Cefotetan
  • Cefoxitin Sodium
  • Cefuroxime

Third-generation cephalosporins

• are resistant to beta-lactamases. They have broad-spectrum antibacterial activity and are effective against P. aeruginosa.
  • Cefdinir
  • Ceftazidime
  • Cefixime
  • Cefotaxime
  • Cefpodoxime
  • Ceftazidime
  • Ceftriaxone
  • Ceftibuten
  • Cefditoren

Fourth-generation cephalosporin

• has broad-spectrum activity, is highly resistant to betalactamases, and has good penetration to cerebrospinal fluid
  • Cefepime

Fifth-generation cephalosporins

• are broad-spectrum drugs effective against MRSA.
• Ceftaroline fosamil
• Ceftolozane and tazobactam.

Cephalosporins Pharmacokinetics

• Cefazolin can be administered via IM and IV, whereas cefaclor is taken orally.
• Cefazolin demonstrates a higher protein-binding than cefaclor.
• Both medications exhibit short half-lives and are primarily excreted unchanged in the urine, accounting for 60% to 80% of the dose.

Cephalosporins Pharmacodynamics

• Cefazolin and cefaclor function by inhibiting bacterial cell-wall synthesis, leading to bactericidal action.
• Cefazolin's onset of action is almost immediate when used intravenously or intramuscularly
• Cefaclor typically reaches its peak concentration in about 30 to 60 minutes when taken orally.
• Probenecid reduces urine excretion of cefazolin and cefaclor.
• The use of tetracyclines or erythromycin may diminish cefazolin and cefaclor effects
• These drugs have the potential to cause false-positive results in laboratory tests

Uses of Cephalosporins

• Cephalosporins are a possible replacement when administering to patients that are allergic to penicillin
• Cephalosporins are used for urinary and respiratory tract infections.

Therapeutic Outcome of Cephalosporins

• Elimination of bacterial infection.

Common Side Effects of Cephalosporins

• Gastrointestinal Diarrhea (cephalosporins cause diarrhea by altering the bacterial flora of the Gl tract)

Others:

• Hepatotoxicity(Transient elevations of liver test results (e.g., AST, ALT, alkaline phosphatase)
• Immune system (opportunistic infections) Secondary infections. Oral thrush, genital and anal pruritus, vaginitis, and vaginal discharge
• Renal Nephrotoxicity- Transient elevations of renal test results (e.g., BUN, serum creatinine).
• Hematologic Hypoprothrombinemia- reduction in circulating prothrombin,
• Electrolyte imbalance If a patient develops hyperkalemia or hypernatremia, electrolyte content of the antibiotics should be considered.
• Vascular Thrombophlebitis. Phlebitis and thrombophlebitis,

Cephalosporins Drug Interactions

• Patients receiving cephalosporins, aminoglycosides, vancomycin, and loop diuretics concurrently should be assessed for signs of nephrotoxicity. Monitor urinalysis and kidney function tests for abnormal results, meaning nephrotoxic potential.
• Antacids- Antacids inhibit the absorption of cefaclor, cefdinir, and cefpodoxime. The antibiotic should be taken 2 hours before or after the antacid.
• Histamine-2 (H2) antagonists.(e.g., cimetidine, famotidine, nizatidine, ranitidine) inhibit the absorption of cefpodoxime and cefuroxime, decreasing the antibiotic effect.

Cephalosporins and other drugs

• Iron supplements and food fortified with iron inhibit the absorption of cefdinir
• Patients receiving probenecid are more susceptible to toxicity because of the inhibition of excretion
• Instruct the patient to avoid alcohol consumption during cefotetan therapy.
• Cephalosporins may interfere with the contraceptive activity of oral contraceptives.

Nursing Assessment for Cephalosporins

• Assess for allergy to cephalosporins or penicillins
• Record vital signs and urine output. Report abnormal findings
• Evaluate laboratory results, including renal and liver function (BUN, serum creatinine, AST, ALT, ALP, and bilirubin)

Nursing Diagnoses for Cephalosporins

• Infection, Risk for
• Noncompliance with the drug regimen
• Nutrition, Imbalanced

Nursing Interventions for Cephalosporins

• The patient's infection will be controlled and ultimately eliminated
• Culture the infected area with cephalosporin therapy
• Report superinfection like ulcers and discharge from the anal or genital area
• Advise patients to ingest buttermilk, yogurt, or an acidophilus supplement

Cephalosporins Patient Teaching

• Keep drugs out of reach of children. Request childproof containers.
• Infuse all IV cephalosporins over 30 minutes

Macrolide Antibiotics

• These are broad spectrum antibiotics that include azithromycin, clarithromycin, eryhtromycin
• These are active against most gram-positive bacteria and moderately active against some gram-negative bacteria
• Used to treat of the respiratory tract, skin, sinus infections, STIs
• At moderate doses macrolides are bacteriostatic and high doses its bactericidal

Erythromycin

• The first macrolide to be created
• Derived from fungus called Streptomyces erythreus
• was first introduced in the early 1950s

Clarithromycin

• Is the drug of choice for the treatment of Mycoplasmal Pneumonia and Legionnaires' Disease

Azithromycin

• is frequently prescribed for STI's and upper and lower respiratory infections

Macrolides Pharmacokinetics

• Erythromycin and Clarithromycin is absorbed in intestinal
• Azithromycin is absorbed incompletely
• Macrolides are excreted in bile, feces and only small amounts are excreted in urine, therefore renal is safe

Macrolides Pharmacodynamics

• Suppress bacterial protein synthesis
• Macrolides have long half-lives and are administered less frequently
• Azithromycin has a larger half life, up to 68hrs
• Immediate release of Clarithromycin is administered twice and the extended release is administered once daily

Side Effects and Adverse Reactions

• Nausea
• Vomitting
• Diarrhea
• Abdominal Cramping
• Super Infection
• Conjunctivitis
• Allergic reactions

Tetracylines

• A broad spectrum antibiotic effective against gram + gram - and many organisms
• works by inhibiting bacterial protein synthesis
• Frequently prescribed for oral use to treat severe infections

Side Effects and Adverse Reactions

• GI disturbances like nausea and vomiting
• photosensitivity may occur in patients taking tetracylines , especially demeclocycline
• Kidneyt toxicity
• minocycline can cause balance problems

Drug Interactions

• can prevent absorption of tetracycline from the GI tract
• to avoid interactino, these should be taken least 2 hours apart
• The activity of oral pills can be lessened