Antibiotic and Anti-Infective Drugs PDF

**ANTIBIOTIC & ANTI-INFECTIVE DRUGS** **Classifications: ** - Bactericidal: drugs are directly lethal to bacterial at clinically achievable concentrations - Bacteriostatic: drugs can slow growth but do not cause cell death **Acquired Resistance to Antimicrobial Drugs**: over time, organi...

**ANTIBIOTIC & ANTI-INFECTIVE DRUGS** **Classifications: ** - Bactericidal: drugs are directly lethal to bacterial at clinically achievable concentrations - Bacteriostatic: drugs can slow growth but do not cause cell death **Acquired Resistance to Antimicrobial Drugs**: over time, organisms develop resistance; may have been highly responsive/then became less susceptible to one or more drugs **4 basic actions** - Decrease the concentration of a drug at its site of action - Inactivates a drug - Alter the structure of drug target molecules - Produce a drug antagonist **Abx Use/Drug-Resistant Microbe Emergence: ** - How abx use promotes resistance: drugs make conditions favorable for overgrowth of microbes that have acquired mechanisms for resistance - **Abx that promote resistance: broad-spectrum agents do the most to facilitate the emergence of resistance ** - **The extent of abx use affects resistance: the more that abxs are used, the faster drug-resistant organisms emerge** - Nosocomial infxns: HAI - Superinfection: new infxn that appears during treatment for primary infxn; because superinfections are caused by drug-resistant microbes, they often are difficult to treat  **Selection of Abxs: ** - identify organism (match the drug w/the bug);  - drug sensitivity of organism;  - host factors (site of infxn, genetics, previous allergic reaction);  - drug may be ruled out owing to: allergy, inability to penetrate site of infxn, patient variables  **Dosage Size/Duration:** abx must be present: at the site of infxn/for a sufficient length of time; abx must be discontinued prematurely; **teach patients to complete full prescription ** **Prophylactic Use of Antimicrobials: ** agents are given to prevent infxn rather than to treat an established infxn:  - surgery  - bacterial endocarditis - neutropenia - **other indications (recurrent UTI's)** **Misuses of Antimicrobial Drugs**: attempted treatment of viral infxns; treatment of fever of unknown origin; improper dosage; treatment in the absence of adequate bacteriologic information; omission of surgical drainage  **Monitoring of Antimicrobial Therapy**: monitor clinical responses/laboratory results; frequency of monitoring should increase w/severity of infxn; clinical indicators of success: reduction of fever, resolution of S/S r/t the affected organ; serum drug levels for toxicity **PENICILLIN** Classification **Abx** ------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA **weaken the cell wall, causing bacteria to take up excessive water/rupture; bactericidal** Uses Active against a variety of bacteria Dose/ Route IM Adverse Effects **Allergic rxn, N/V/D** Drug Interactions Aminoglycosides, bacteriostatic abxs, probenecid Patient Education Bacterial Resistance: inability of penicillin to reach their target; inactivation of penicillin's by bacterial enzymes, Production of penicillin-binding proteins (PBPs) that have a low affinity for penicillin's, **most common allergy** **PENICILLIN G (BENZYLPENICILLIN)** Classification  **Abx** -------------------- --------------------------------------------------------------------------------------------- MOA **weaken the cell wall, causing bacteria to take up excessive water/rupture; bactericidal** Uses Bactericidal to numerous gram +/some gram - organisms  Dose/ Route IV Adverse Effects  **Allergic rxn, N/V/D**, HA, Least toxic of all abxs Drug interactions  Aminoglycosides, bacteriostatic abxs, probenecid  **Penicillin Allergy: ** - development of penicillin allergy; skin tests for penicillin allergy; management of patient's w/a hx of penicillin allergy;  - assess for penicillin allergy in each patient who will be receiving penicillin  - if hx of mild reaction, consider cephalosporin;  - if hx of anaphylaxis, avoid administration of penicillin or cephalosporins - Types:  - immediate (reaction in 2-30 minutes);  - accelerated (reaction in 1-72 hrs.);  - delayed (reaction takes days or weeks to develop) - **Anaphylaxis:** laryngeal edema, bronchoconstriction, severe hypotension - **Tx:** epinephrine, respiratory support; prevention: skin testing **AMOXICILLIN** Classification  Penicillin; **broad-spectrum penicillin**  ------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA **weaken the cell wall, causing bacteria to take up excessive water/rupture**, bactericidal, Same antimicrobial spectrum as penicillin G, plus increased activity against certain gram - bacilli (H. influenzae, E. coli, Salmonella, & Shigella) Uses **common abx in peds -- Otitis media** DOC Pregnant/breastfeeding women, **Otitis media** Adverse Effects  Rash, Diarrhea Drug interactions Aminoglycosides, bacteriostatic abxs, probenecid Patient Education Reduce does for renal impairment, do not give for staph infxn (d/t increased risk chance of resistance), **more preferred over penicillin due to being broad spectrum & oral** **NAFCILLIN** Classification  Penicillin; **Penicillinase-resistant penicillin** ------------------- --------------------------------------------------------------------------------------------- MOA **weaken the cell wall, causing bacteria to take up excessive water/rupture**, bactericidal Dose/ Route IV only, erratic/incomplete Adverse Effects  Rash, Diarrhea Drug interactions Aminoglycosides, bacteriostatic abxs, probenecid  **Penicillin Combinations** **Amoxicillin/clavulanate (Augmentin) & Piperacillin/tazobactam (Zosyn) -- watch for difficulty of breathing** **CEPHALOSPORINS (CEPHALEXIN, CEFOXITIN, CEFOTAXIME, CEFTAZIDIME, CEFTRIAXONE)** +-----------------------------------+-----------------------------------+ | Classification  | **Beta-lactam abx** | +===================================+===================================+ | MOA | Binds to penicillin-binding | | | proteins (PBPs), **weaken the | | | cell wall, causing bacteria to | | | take up excessive | | | water/rupture,** most effective | | | against cells undergoing active | | | growth/division, bactericidal | +-----------------------------------+-----------------------------------+ | Uses | 1^st^ gen (prophylaxis against | | | infxn in surgical patients; | | | rarely used for active infxns) - | | | Cephalexin -- given for skin | | | infxn | | | | | | 2^nd^ gen (rarely used for active | | | infxn); less sensitive for | | | destruction - Cefoxitin | | | | | | 3^rd^ gen (highly active against | | | gram - infxns, able to penetrate | | | CSF) -- Cefotaxime, Ceftriaxone | | | (Rocephin) = broad spectrum | | | (gonorrhea), **Ceftazidime | | | (Fortaz) = most effective against | | | of pseudomonas aeruginosa** | | | | | | 4^th^ gen (commonly used to treat | | | hospital-associated pneumonias, | | | including those caused by | | | resistant organism Pseudomonas) - | | | Cefepime | | | | | | 5^th^ gen (infxns associated | | | w/MRSA) - Ceftaroline | +-----------------------------------+-----------------------------------+ | Dose/ Route | IV | +-----------------------------------+-----------------------------------+ | Adverse Effects  | Hypersensitivity (rash after | | | several days of 1^st^ dose), | | | **Pseudomembranous Colitis | | | (C-diff -- bloody diarrhea, abd. | | | pain, fever),** Thrombophlebitis | +-----------------------------------+-----------------------------------+ | Drug Interactions | Bleeding tendencies (interferes | | | w/vit. D), | +-----------------------------------+-----------------------------------+ | Patient Education | Generations 3,4,5 Cross the | | | BBB/CSF, higher you go the more | | | specific/effective, **avoid if | | | allergic to penicillin** | +-----------------------------------+-----------------------------------+ **VANCOMYCIN** Classification **Own class** ------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA Inhibits cell wall synthesis, Bacteriostatic Uses Severe infxn only; MRSA, Staphylococcus epidermidis, C. diff, Only Gram + DOC HAI MRSA Dose/ Route IV Therapeutic range 10-20 Adverse Effects Ototoxicity (reversible or permanent), **"red man" syndrome** (**admin too fast, they flush & turn red, swell, fever & admin over 1hr -- notify MD),** thrombophlebitis, thrombocytopenia, allergy, Nephrotoxicity Drug Interactions Avoid other Renal Toxic drugs Aminoglycosides Patient Education Levels must be tested 30 min before admin 4^th^ dose **TETRACYCLINES (DEMECLOCYCLINE, DOXYCYCLINE, MINOCYCLINE)** Classification **Broad Spectrum abx** ------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA Suppress growth by inhibiting protein synthesis, Bacteriostatic Uses Tx of infectious disease, Tx of acne, PUD, Periodontal disease, RA, Mycoplasma pneumoniae, Lyme disease, Anthrax, H. pylori DOC Doxycycline -- Renal impaired pts, Minocycline -- RA, Rickett's/Rocky Mountain spotted fever Dose/ Route IV Adverse Effects GI irritation (N/V/D), **effects on bone/teeth (discoloration of teeth),** Superinfection, hepatotoxicity, renal toxicity, photosensitivity/other effects Drug Interactions Ca supplements, milk products, iron supplements, magnesium-containing laxatives/**most antacids (bind to the gut/decrease absorption)** Patient Education **Avoid Ca/antacids/etc. 1 hr. before & 2 hrs. after or 2 hrs. before & 6 hrs. after, best to avoid altogether though**, **do not give to pregnant women or children under 8** **MACROLIDES (ERYTHROMYCIN, AZITHROMYCIN)** Classification **Broad-spectrum abx** ------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA Inhibits protein synthesis; usually bacteriostatic but can be bactericidal Uses acute diphtheria, *Corynebacterium diphtheria*, chlamydial infxns, ***M. pneumoniae***, group A *Streptococcus pygoenes*; active against most gram +/some gram - bacteria; use as an alternative to penicillin G in pts w/penicillin allergy  DOC **Whooping cough (pertussis)** Dose/ Route PO Adverse Effects **Most common SE - GI effects (N/V/D),** QT prolongation/sudden cardiac death, superinfections, thrombophlebitis, transient hearing loss Drug Interactions Hepatic Cytochrome P450, Warfarin, Theophylline, Bipolar medications, AED\'s **\*\*\*azithromycin treats chlamydia** **CLINDAMYCIN (CLEOCIN)** Classification **Broad-spectrum abx** ------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA Inhibits protein synthesis  Uses Active against gram +/some gram - bacteria (Certain anaerobic infxns outside the CNS); alternative to penicillin Adverse Effects **Superinfections (Cdiff, Pseudomembranous Colitis) -- Stop the med, then notify provider**, hepatic toxicity, blood dyscrasias (elevated WBC's), diarrhea, hypersensitivity reactions Patient Education **Can promote severe *C. diff*-associated diarrhea (CDAD**) -- fatal, Poor penetration of CSF/BBB, not affected by food **LINEZOLID (ZYVOX)** Classification **No class** ------------------- --------------------------------------------------------------------------------------------------------------------------------------------------- MOA Bacteriostatic inhibitor of protein synthesis Uses Active against multidrug-resistant, gram + pathogens (ex: VRE, MRSA); active against aerobic & facultative gram + bacteria Dose/ Route IV (more effective), PO Adverse Effects **N/V/D, HA,** **Myelosuppression (reversible),** Prolonged therapy of 5+ months (reversible optic neuropathy/irreversible peripheral neuropathy) Drug Interactions **MAOIs**; cross-resistance w/other agents unlikely Patient Education Well tolerated, CBC weekly for Myelosuppression **AMINOGLYCOSIDES (GENTAMYCIN, AMIKACIN)** Classification **Narrow-spectrum abx** ------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ MOA Disrupts bacterial protein synthesis Uses Aerobic gram - bacilli (E Coli, Pseudomonas aeruginosa) DOC **reversal w/IV infusion** of a Ca salt (ex. **Ca gluconate**) Dose/ Route PO Adverse Effects **Nephrotoxicity, Ototoxicity (Reversible Tinnitus**), Hypersensitivity reactions, **Neuromuscular blockade**, **Blood dyscrasias** (lower number of all blood levels) Drug Interactions Avoid all Nephro/ototoxic drugs, Avoid skeletal muscle relaxants Patient Education Give PO if organism is in intestine, Crosses BBB poorly (don't give to pt's w/meningitis), don't give to pregnant women **Serum Levels** - The same aminoglycoside dose can produce a very different plasma level in different patients - Peak levels must be high enough to kill bacteria; trough levels must be low enough to minimize toxicity - Samples for... - peak levels: 30 minutes after IM injection or IV infusion - Trough levels: depends on dosing schedule - Divided doses: take sample just before the next dose - Once-daily doses: draw a single sample 1 hr. before the next dose; value should be very low -- preferably close to zero **AMIKACIN (AMIKACIN)** Classification **Aminoglycosides  ** ----------------- --------------------------------------------------------------------------------------------------------------------- MOA Disrupts bacterial protein synthesis Uses active against the broadest spectrum of gram - bacilli/is the least vulnerable to inactivation by bacterial enzymes DOC Gentamicin resistant drugs Adverse Effects **Nephrotoxicity, ototoxicity ** **GENTAMICIN (GARAMYCIN)** Classification **Aminoglycosides  ** ----------------- ---------------------------------------------------------------------------------------------------------------------------------- MOA Disrupts bacterial protein synthesis Uses Treat serious infxns caused by aerobic gram - bacilli (Pseudomonas aeruginosa, E. coli, Klebsiella, Serratia, Proteus mirabilis) Adverse Effects **Nephrotoxicity, ototoxicity ** **SULFONAMIDES ** Classification **Broad-spectrum abxs** ------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA Suppress bacterial growth by inhibiting tetrahydrofolic acid, a derivative of folic acid or folate Uses Nocardiosis, *Chlamydia trachomatis*, conjugation therapy for toxoplasmosis/malaria, ulcerative colitis DOC UTI Dose/ Route Systemic absorption Adverse Effects hypersensitivity reactions (Stevens-Johnson syndrome), hematologic effects, kernicterus (Hyperbilirubinemia in babies/Avoid in late Prego, breastfeeding/children under 2 months), renal damage from crystalluria Drug Interactions metabolism-related interactions, cross-hypersensitivity Patient Education Avoid if allergic to sulfa **SILVER SULFADIAZINE (SILVADENE)** Classification **Sulfonamides  ** ------------------- --------------------------------------------------------------------------------------------------------------------------------- MOA Inhibits the synthesis of folic acid Uses **Suppress bacterial colonization in pts w/2^nd^ /3^rd^ degree burns ** Dose/ Route Systemic absorption Adverse Effects Hypersensitivity reactions (Stevens-Johnson syndrome), hematologic effects, kernicterus, renal damage from crystalluria Drug Interactions Metabolism-related interactions, cross-hypersensitivity Patient Education Application of silver sulfadiazine usually is pain free, causes permanent blue-green coloration of the skin, Mafenide: acidosis **TRIMETHOPRIM/SULFAMETHOXAZOLE (BACTRIM)** Classification **Sulfonamides** ------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA Inhibits sequential steps in bacterial folic acid synthesis, making it much more powerful than TMP or SMZ alone Uses UTI, otitis media, bronchitis, shigellosis, pneumonia caused by Pneumocystis jiroveci, Pneumocystis pneumonia, GI infxn, chronic/recurrent infxn DOC Acute UTI Adverse Effects CNS effects (HA, Depression, Hallucination, etc.), GI (N/V), Rash, Hyperkalemia (Only w/ high doses & renal impairment), Hypersensitivity reactions (Stevens-Johnson syndrome), Blood dyscrasias, Kernicterus, Renal damage: crystalluria Patient Education **Do not take if allergy to sulfa drugs** **Acute Cystitis** - Lower UTI that occurs most in women of child-bearing age - s/s: dysuria, urinary urgency/frequency, suprapubic discomfort, pyuria/bacteriuria - DOC - Uncomplicated: TMP/SMZ (Bactrim) or nitrofurantoin - Communities where resistance exceeds 20%: fluoroquinolones (ciprofloxacin, norfloxacin) - Adherence is a concern: single-dose Fosfomycin **Acute Uncomplicated Pyelonephritis** - Infxn of the kidneys -- A lot of Bacteria in Urine 100,000+ - Common in young children, older adults, women of child-bearing age - s/s: fever, chills, severe flank pain, dysuria, urinary frequency & urgency, pyuria/ usually bacteriuria - Mild to moderate infxn: TMP/SMZ (Bactrim), trimethoprim alone, ciprofloxacin/levofloxacin - Severe infxn: hospitalization/IV abxs **Acute Bacterial Prostatis** - Inflammation of the prostate caused by local bacterial infxn - s/s: high fever, chills, malaise, myalgia, localized pain/various urinary tract symptoms - Responds well to antimicrobial therapy. Drug selection/route depend of organism/severity. - E. coli: IV agent (fluoroquinolone such as ciprofloxacin followed by oral agent (doxycycline or fluoroquinolone) - Vancomycin-sensitive E. faecalis: IV ampicillin/sulbactam then PO amoxicillin, levofloxacin, or doxycycline **NITROFURANTOIN (MACRODANTIN)** Classification **Urinary tract antiseptics** ------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA Uses Lower UTIs (bladder/urethra), **prophylaxis, recurrent lower UTIs**, Bacteriostatic (low concentration); bactericidal (high concentration) Adverse Effects GI effects (N/V/D, give w/milk or meals), Pulmonary reactions (SOB, chills fever, cough), Hematologic effects (Hemolytic anemia), Peripheral neuropathy, **Hepatotoxicity**, Birth defects, Nephrotoxic (brown color urine) Patient Education **Avoid in pts w/liver disease**, renal disease **FLUOROQUINOLONES** Classification **Broad-spectrum agents w/multiple applications** ------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------- MOA Disrupt DNA replication/cell division, Bacteriostatic Uses Last resort  Dose/ Route PO Adverse Effects **Tendon rupture (low risk) -- Stop & Notify MD, usually affects Achilles tendon, Phototoxic** Drug Interactions **Avoid antacids** Patient Education Resistance develops slowly, **Avoid in Pts \