Drug Therapy with Antibacterial Agents

Tetracyclines & Sulfonamides

• Older, broad-spectrum bacteriostatics

• Rarely used for systemic infections

  • Due to microbial resistance

  • Development of more effective/less toxic medications

• Urinary antiseptics

  • Used only in UTIs

Pharmacokinetics Tetracyclines

Penetrate microbial cells, inhibiting protein synthesis

Pharmacokinetics Sulfonamides

• Halt multiplication of new bacteria

• do not kill mature, fully formed bacteria

Tetracyclines

• tetracycline (Achromycin)

• demeclocycline (Declomycin)

• doxycycline (Doxychel, Vibramycin)

• minocycline (Minocin)

• xytetracycline (Terramycin)

• Broad spectrum: gram – and gram +

Tetracyclines contraindications

Contraindicated during pregnancy or in children less than 8 yo –may harm the unborn baby or cause permanent tooth discoloration later in the baby’s life

Tetracyclines Indications for Use

• Drug of choice in specific infections

  • Cholera, Rocky Mountain spotted fever, syphilis, typhus, H. pylori, mycoplasma, rickettsia, etc.

• Useful in animal bites, Lyme’s disease

• Chlamydia infections, adjunct in STD treatment, prophylaxis/treatment of anthrax(ciprofloxacin)

• Long-term acne adjunct treatment, substitute for PCN in hypersensitivity

Tetracyclines Nursing Interventions

• Renal

• Drug interactions

Tetracyclines Nursing Education

• Avoid sunlight

• Take on empty stomach

• Drug interactions

Sulfonamides

• sulfadiazine

• sulfamethazine

• sulfisoxazole

• Fosfomycin

• Silver sulfadiazine (Silvadene)

• Trimethoprim–sulfamethoxazole (Bactrim)

• Broad spectrum: gram - and gram + Bacteriostatic

  • streptococcus pyogenes

  • some staphlococcal strains

  • influenzae

  • toxoplasmosis

Sulfonamides Indications

• UTI caused by E. coli, Proteus, Klebsiella organisms

• in combination to treat chronic bronchitis

• Ulcerative colitis, other uncommon infections

• Topically

  • Prevention of burn wound infections

  • Ocular and other soft tissue infections

Trimethoprim-Sulfamethoxazole (TMP-SMZ)

• Resistance common

• Avoid use with renal impairment

Trimethoprim-Sulfamethoxazole (TMP-SMZ) treats

• Lower respiratory tract (pneumonitis)

• UTI

• Prostatitis

• Infectious diarrhea

• Bone and joint infections

  • Elderly at higher risk

Trimethoprim-Sulfamethoxazole (TMP-SMZ) nursing intervention

• Pregnancy

• Age

• Renal status

• Drug interactions

Trimethoprim-Sulfamethoxazole (TMP-SMZ) nursing education

• Skin

• Caution with OTC

Urinary Antiseptics

• May be bactericidal because of local effects produced by high concentration levels in renal tubules and urine

• Not used for systemic infections as they do not attain therapeutic plasma levels

• Used only for UTIS

• Encompasses:

  • Nitrofurantoin, Phenazopyridine

Nitrofurantoin

• Administer with food

• do not use in older adults

  • Renal, pulmonary, hepatic toxicities

• do not use in pregnancy 1st trimester or weeks 38-term

• Nonspecific St and T wave changes, CNS changes

• Brown urine

Phenazopyridine

• Urinary analgesic

• Administer with food

• Orange urine

• Black Box Warning:

  • Report yellow skin = indicates build up of drug in system

  • Patients should also report sore throat, fever, bruising, bleeding

• Contraindications: renal insufficiency and hepatitis

Macrolides

• Widely distributed into body tissues and fluids

• Bacteriostatic or bactericidal

  • Depending on drug concentration in infected tissues

• Effective against gram(+) cocci

Types of Macrolides

• Azithromycin (Zithromax)

• Clarithromycin (Biaxin)

• Erythromycin base (E-mycin)

Macrolides Indications

• Respiratory tract and soft tissue infections

• PCN substitute for hypersensitivities

• Prophylaxis

  • Rheumatic fever, pertussis, chlamydial conjunctivitis in newborns

• Treatment for other infections

  • GU infections, bacterial sinusitis; H. pylori

Miscellaneous Antibacterials

• Chloramphenicol

• Clindamycin

• Daptomycin

• Linezolid

• Metronidazole

• Quinupristin–dalfopristin

• Rifaximin

• Spectinomycin

• Vancomycin

Principles of Therapy

• Culture and susceptibility reports determine if resistance is present

  • Important pre-pharmacotherapy

• Macrolides and ketolides have relatively narrow spectrum of activity.

  • Preventing toxicity vital

Aminoglycosides

Widely used to treat serious gram(−) infections for many years

Fluoroquinolones

• Synthesized through an addition to quinolone structure

  • Quinolones are older drugs originally used for treatment of UTIs only.

Aminoglycosides Mechanism of action

Penetrate bacterial cell walls, preventing bacterial synthesis of proteins necessary for function, replication.

Aminoglycosides Indications for use

• Serious systemic infections

  • Septicemia

  • Respiratory tract infections

  • Urinary tract infections

  • Intra-abdominal infections

  • Osteomyelitis

• Susceptible aerobic gram(−) organisms

Aminoglycosides bacteria tx

• Bactericidal agents

• Gram –aerobic

  • Pseudomonas and Proteus species

  • Coli

  • Klebsiella

  • Enterobacter

• Select Gram+

Gentamycin

• Most common

• Rapid absorption IM, IV

• Accumulates in renal tubules and inner ear

• BLACK BOX warning

• Peak and Trough levels

Gentamycin Uses

• Meningitis, endocarditis

  • in combination with beta-lactam ATBs

• Intestinal bacteria suppression

  • Pre-op bowel surgery

  • Hepatic coma treatment

• Topically (eye, skin)

Gentamycin Nursing Interventions

• PCN

• Usually IV

• Peak & trough levels MUST be collected when ordered

• Labs

• Medications

Gentamycin Nursing Education

• Hydration

• Eye drops

• Ototoxicity

Fluoroquinolones

• Synthetic bactericidal active against gram(−) and gram(+) organisms

• Well absorbed when given orally

• Achieve therapeutic concentrations in most body fluids

Fluoroquinolones Mechanism of action

• prevents DNA enzyme synthesis

• Metabolized mainly in the kidneys, to some extent in the liver

  • 30 to 60% of oral dosing excreted unchanged in urine

Fluoroquinolones Indications

• Infections

  • Respiratory

  • GU

  • GI

  • Bone/Joints

  • Skin/soft tissue

Fluoroquinolones Contraindications

• Hypersensitive

• Children less than 18

• Pregnant/lactating women

  • Category C

• Drug selection: based on bacteria

Ciprofloxacin

• Bactericidal

• Gram (–)

• Treats multiple infections

• no longer recommended for gonococcal disease

• FDA recommends use be limited to complicated infections

• Black Box Warning: tendinitis, tendon rupture, peripheral neuropathy, CNS and cardiac effects, dermatologic, hypersensitivity reactions especially in those > 60 yrs. of age. QT interval prolongation

• Many drug and dietary interactions

Ciprofloxacin Nursing Interventions

• Renal disease

• Drug interactions

• Can be crushed

• Labs

Ciprofloxacin Nursing Education

• Do not take with antacids

• Avoid sun exposure

Beta-lactams

• Most widely used group of antibiotics

• All antibiotic agents with a beta-lactam ring

• Bacteria synthesize beta-lactamase

• PCN, cephalosporins, carbapenems, monobactams

• What hinders these antibiotics: Beta-lactamases

  • Counteract examples:

    • Clavulanate, sulbactam, tazobactam

Penicillins

• Safe, effective, widely used ATB

• First antibiotic developed

  • Had to be given parenterally initially

    • Due to it being destroyed by gastric acid.

    • Injections were painful.

  • Extensive use produced drug-resistant strains of Staphylococci.

Penicillins Post absorption

• Widely distributed

• Achieve therapeutic concentrations in most body fluids

  • Not usually obtained in intraocular and CSF unless inflammation present

• Rapidly excreted by kidneys

Penicillins Indications for use

• Bacterial infections caused by susceptible organisms

• More effective in gram(+) than gram(–) infections

• Skin/soft tissue, respiratory, GI, and GU infections

• Incidence of resistance continues to increase to:

  • Streptococci

  • Staohylococci

  • Other microorganisms

Penicillins Contraindications for use

• Hypersensitivity/allergic reaction to any penicillin preparation

• Potential exists for cross-allergenicity with cephalosporins and carbapenems

  • in life-threatening allergic reactions to PCN, cephalosporin and carbapenem use is to be avoided.

Penicillin combinations

• Piperacillin, Zosyn

• Broad-spectrum ATB

  • Especially against gram(–) organisms

• Available orally for UTIs, prostatitis

• IV dosing is available

• Most can be given IM.

Penicillin Nursing Interventions

• Empty stomach

  • Exception Augmentin

• Should be given as directed

• Assess for home meds & drug interactions

Penicillin Nursing Education

• Oral solution is ok refrigerated 14 days

• Take until completed

• Must use alternatives for birth control

• NVD considerations

Cephalosporins

• Widely used group of medications

  • Derived from a fungus

• Broad-spectrum ATB with activity against gram(+) and gram(−) bacteria

  • More active against gram(−) compared with PCNs

• Widely distributed into most body fluids and tissues

  • Maximum concentration in the liver and kidneys

• 4 generations

Cephalosporins Clinical indications for use

• Surgical prophylaxis

• Treatment of infections

  • Respiratory tract, urinary tract

  • Skin, soft tissues

  • Bones, joints

  • Brain, spinal cord; bloodstream (septicemia)

Cephalosporins contraindications

• Previous anaphylactic reaction to PCN

• Cross-sensitivity low in those with delayed reactions to PCN

  • Skin rash

• Cephalosporin allergy

Cephalosporins Generations

• 1st generation - gram+; poor gram-

  • cefazolin (Ancef), cephalexin (Keflex)

• 2nd generation – gram-, less gram+, & anaerobic bacilli

  • cefaclor (Ceclor), cefprozil (Cefzil), cefuroxime (Zinacef, Ceftin)

• 3rd generation - gram-; more resistant to B-lactamase; less gram+

  • cefdinir (Omnicef), ceftazidime (Fortaz), ceftriaxone (Rocephin)

• 4th generation – gram+, gram-, and more resistant to beta-lactamase

  • cefepime (Maxipime)

• 5th generation – active against resistant gram+ organisms

  • Ceftaroline (Teflaro) IV CAP, skin. Active against gram + e.g. vancomycin resistant S. aureus (VRSA), vancomycin-insensitive S. aureus (VISA), heteroresistant (VISA), MRSA

Cephalosporins Nursing Implications

• Interventions

  • Renal dose

  • Safe in

    • Older adults

    • Children

  • Given 1 hour prior to surgery

• Look at drug interactions

• Can be taken w/milk & H20

• Avoid antacids

• 2 hrs before or after

• OCP’s

• Monitor diarrhea

Carbapenems

• Broad-spectrum, bactericidal beta-lactam antimicrobials

• 4 drugs

  • Imipenem - cilastatin

  • Ertapenem

  • Meropenem

  • Doripenem

Carbapenems main use

• tx of infections caused by resistant organisms to other drugs.

• Excreted through kidneys

Carbapenems Contraindications

Hypersensitivity to carbapenems, potential for cross-reactivity with those with severe penicillin allergy due to common beta-lactam ring. Patients with severe shock or atrioventricular (AV) block should not receive IM form (contains lidocaine).

Monobactams

• Aztreonam (Azactam)

• Active against gram(−) bacteria

• Active against many strains that are ATB resistant

• Does not cause kidney damage or hearing loss (as can aminoglycosides)

• Limited cross-allergencity between itself and other beta-lactam antibiotics

Monobactams Indications for use

Urinary tract, skin/skin structures, lower respiratory tract, intra-abdominal, and gynecologic infections, septicemia

Antibacterial Therapy Goal of therapy

Prevent/treat infections caused by pathogenic organisms

Antibacterial Therapy Drug selection

• Depends on organism causing infection

• Severity of infection

• Other factors