Drug

Subtype

Mechanism

Resistance

Microbial use Drugs acting against cell wall

Adverse Reactions

Misc

Penicillin G Inhibits growth by inhibiting cross-linkage of petidoglycan. Cell is then lysed by bacterial Nafcillin, oxacillin, autolysins. Pencillin bind to "PBP" responsible for methicillin transglycosylase. Wide biodistribution, but can't cross CNS unless meninges are inflamed. Can cross placenta. Ampicillin Synergistic with aminoglycosides

Pencillin

S. pyogenes, S viridians, S. pneumo, N. meningitis, C. perfriengens, C. teani, T. pallidum, leptospira, actinomyces, enteroccus. Effective against neurosyphilis and fetal -lactamase typically plasmidsyphilis borne and seen in S. aureus. Ghave some as well. Oxa, naf and meth are -lactamase resistance pencillin. Methicillin resistant Infections due to S. aureus (antistaphylococcal bacteria (S. aureus, S. penicillins), but not MRSA pneumo, Enterococcus faecalis, N. meningitis, N. gonorrhoae) have a chromosomal mutation in PBPs. Penicillin tolerance is due to decease in autolysins. E. coli, P. mirabilis, H.influenza, M. catarrhalis, Additionally, some pseudomonas L monocytogenes, shigella, salmonella, in addition to normal penicillin targets have mutations in porins and efflux pump P. aeruginosa, Serratia, Enterobacter, and Acinetobacter

Allergic reactions (2-2.5% for aqueous, 0.3% oral): can become antigenic via haptenprotein formation or polymerization; IgE declines with Naf = 90% excreted in time. All four hypersensitivities bile. Methicillin not used have been observed: I = due to toxicity urticaria, flushing, puritus, laryngeal edema, anaphylaxis 20 Acid stable, excreted min after admin. Accelerated can more slowly than occur up to 48 hrs, with urticarial reactions. II = hemolytic anemia. penicillin G. Considered III = Three days post-admin, skin extended spectrum. Synergistic with rashes, fever, nephritis, serum gentomicin sickness. IV = contact dermitis Rapidly excreted

Penicillin V = semisynthetic, acid stable. All generally excreted rapidly by kidney (10% filtered, 90% secreted) although probenecid can inhibit secretion.

Ticarcillin

1st generation

Gram+ coci (except enterococci) and some G(E. coli, K. pneumoniae, Proteus mirabilis); UTI's, community acquired soft-tissue. Mostly used when pt needs pencilin but is allergic More G- than first gen (H. influenza and M Similar mechanism of resistance Penicillin analogues; catarrhalis); used for otitis, sinusitis, nonas penicillin. Infeffective against resistant to -lactams. MRSE/A, L. monocytogenes, C. serious community acquired respiratory, pelvic Similar biodistribution as and diabetic foot inf. difficile, and enterococci. Not penicillin, although only susceptible to Staph 3rd gen capable of penicillinase, although Strep, enterobacteriaceae, H. influenza, N. crossing meninges, susceptible to broad spectrum gonnorrhoea, chancroid, Lyme disease. inflamed or otherwise. lactamases Ceftriaxone preferred drug for gonorrhea, Lyme arthritis, p-resistant pneumococci, and meningitis. Ceftazidime is active against P. aeruginosa. Cefotaxim penetrates CSF. More resistant to -lactamase than 3rd gen.

Cefazolin, cephalexin, cephradin

2nd generation Cephalosporin

Similar to penicillin. Hx of penicillin allergy --> 4x likelihood of cephalosporin reaction (8%). NEVER GIVE WITH GENTAMICIN (renal toxicitiy). Causes alcohol intolerance, platelet disfynction

Cefoxitin, ceforoxime, cefaclor

3rd generation

Cefotaxim and ceftriaxone enter CSF. Ceftriaxone excreted in bile (used in patients with renale insufficiency Cefepime Amox/ticarcillin + clavulanic Amp + sulbactam Piperacillin + tazobactam

4th generation

Beta-lactamase inhibitors

Clavulanic acid, sulbactam, tazobactam

Suicide inhibitors of lactamases

Do not inhibit activity in pseudomonas, enterobacter, citrobacter, serratia

Works on E. coli, Klebsiella, Proteus, H. influenza, Moraxella catarrhalis, Providencia, Bacteroides, S. aureus Active against enterobacteriaceae but inactive vs. G+ and anaerobes. "Magic bullet for G- aerobic bacteria"

Monocyclic lactams

Aztreonam

-lactamase resistant drug Active against penicillinresistant strains (lactamase resistant) Susceptible to metallo-lactamase Enterococci resistance due to plasmid (codes for enzyme that converts D-Ala to D-Lac), which can be transmitted to S. aureus. Intermediate resistance due to thickened cell wall

Little likelihood of cross-allergy with penicillin Used with cilastatin (renal inhibitor) to prevent excretion

Carbapenems

Imipenem, meropenem

Penicillin-resistant pneumococci and enterobacter (broadest range of activity known to man)

Renal failure --> seizures

Vancomycin

--

Binds tightly to D-ala-Dala peptides. Rapidly bacteriacidal

Effective against G+, used against MRSA and MRSE, C. difficile-induced colitis

Thrombophlebitis, ototoxicity, Vancomycin resistance -nephrotoxicity. Non-IgE mediated > daptomycin, histamine release --> "Red man quinopristin/dalfopristin, syndrome" and linezolid

Daptomycin

--

Acts as ion channel, causing perforation and rapid depolorization of membrane. Bactericidal (concentration dependent) Phosphatase that inhibits cell well synthesis

Wide spectrum; used for vancoresistant bacteria, soft-tissue infections, right sided endocarditis. Cannot be used in pneumonia due to surfactant inactivation --

VRSA and VISA bacteria

--

--

Bacitracin

--

G+ bacteria

Nephrotoxic and ototoxic if given systemically

Topical and ophthalmological use only Excreted by kidney. Used synergistically with fluoroquinolones, aminoglycosides and lactams

Fosfomycin

--

Analogous to PEP which inhibits synthesis of cell wall monomers.

Bacterial enzymes can cleave it

UTI infections (single dose)

--

Translation inhibiting drugs Chelates divalent ions Binds to and damages bone and (can't be taken with Drug of choice for Mycoplasma pneumonia, teeth, gastrointestinal (nausea, calcium, dairy, antacids). chlamydia, rickettsia, and some spirochetes; vomiting, diarrhea), leads to Tigecycline = formerly used against Vibrio, but resistance overgrowth of psuedomonas, glycylcycline, which can has been demonstrated. Used for Helicobacter proteus, staph, clostridia and affect tetracyclinepylori. Combined with aminoglycoside for candadid (colitis), hepatic toxicity resistant bacteria tulerimia, plague and brucellis in pregnant women. Dizziness (although Proteus and and vertigo with doxy Pseudomonus still resistant) Gentamicin is used in treatment of rare lymphoid disease; cannot penetrate CSF, even if inflamed. Synergistic with ampicillin

Tetracyclines

Doxycycline, minocycline, tigecycline

Binds to 30S ribosome, blocking entry of tRNA

(1) Impaired influx/increased efflux; G- = Tet(AE) pumps , Staph = Tet(K) pumps, G+ = Tet(M) pump. (2) Ribosome protection (3) Enzymatic inactivation

Aminoglycosides

Gentamicin, amikacin, tobramycin, streptomycin

Diffuses readily across some G- membrane, as well as through an oxygen1) Decreased uptake of drug (2) dependent system. Binds Plasmid encoded enzymes to 30S ribosome, preventing formation and depleting polysomes Plasmid-encoded. (1) Reduced permebeability/active efflux (2) production of esterase (seen in Entero) and (3) modification Inhibitory or bactericidal, of ribosomal binding site via binds to 50s ribosome, chromosomal or methylase. preventing translocation Methylase confers resistance to and initiation complex clindamycin and streptogramin (MLS-type B); methylase is inducible, so can cause false positives Similar to erythromycin, but with addition of methyl group Addition of methylated nitrogen to erythro --

Effective against G- bacilli, including Pseudomonas aeruginosa. Also used in cases of tularemia. Synergistic with -lactam or vancomycin

Ototoxicity, nephrotoxicity, paralysis, contact dermititis (neomycin)

Erythromycin

Effective against G+, as well as Neisseria, Bordetella, Bartonella and cat scratch fever. Drug of choice for corynebacterial infection (diphtheria, corynebacterial sepsis, erythramasma)

Can inhibit P450, leading to drug interactions. Gastrointestinal problems common

Used as pencillinsubstitute for penicillin allergic patients

Macrolides Clarithromycin

Same as above, except active against Mycobacterium avium Same as above, except highly active against chlamydia

Lower incidence of gastrointestinal problems compared to erythro --

-Low serum concentration, but penetrates most tissues including CNS --

Azithromycin

--

Clindamycin

Binds to the same 50S ribosome as erythromycin

Enterococci and G- aerobic bacteria are resistant

Community acquired MRSA, treatment by Diarrhea, nausea, skin rashes bacteroides and other mixed infection with impaired liver function. Can participants. Often used in conjunction with lead to Pseudomembranous aminoglycoside and cephalosporin to treat colitis (Clostridium difficile penetrating abdomen/gut wounds exotoxin induced) !!! Wide spectrum, not active against chlamydiae. Highly toxic, rarely used. Causes Can be bacteriocidal against H. influenzae, N. bone marrow and GI meningitidis and some bacteroides. Used disturbances. Especially toxic for against ricketsial infection (typhus and infants, who lack glucuronic acid RMSF) conjugation Inhibits P450, leading to drug interaction with warfarin and other drugs

Chloramphenicol

--

Inhibitor of protein synthesis; binds to 50S ribosome. Bacteriostatic.

Plasmid encoded enzyme, chloramphenicol acetyltransferase, inactivates drug

Capable of penetrating the CNS, used topically for eye infections

Streptogramins

Quinupristindalfopristin

Combo of streptogramin Efflux resistance found in E. A and B, which each bind faecalis. Erythromycin resistance Approved for vanco resistant E. faecium (not to different sites on 50S generally precludes resistance to E. faecalis), as well as VRSA ribosome Streptogramins (see above) Binds to 50S ribosomal subunit, preventing binding of 30S and complex formation No cross-resistance, but some instances of reduced binding VRSA, as well as vanco resistant E. faecium AND faecalis

Oxazolidinone

Linezolid

Does not inhibit P450, but should not be taken with serotonin 100% bioavailable orally reuptake inhibitors; welltolerated with some reports of GI problems.

Miscellaneous antimicrobial Effective against systemic infections, with the exception of MRSA, enterococci, and pneumo. Useful in Enterobacteriaceae and G- bacilli (traveler's diarrhea from E. coli). Oral absorption impaired by cations (don't take with meal), true of all fluorquinolones

Ciprofloxacin Cross-resistance is rare from other antibiotics from different classes, but common across the class. MRSA is often resistant Enter by passive diffusion (1) Decreased affinity to gyrase across porins. Inhibit and topoisomerase IV brough on replication by interfering by mutation (2) Decreased with gyrase accumulation due to efflux. -(topoisomerase). Two additional low-resistance, Bactericidal, plasmid borne adaptations: (3) concentration dependent. Qnr protective protein from plasmid (4) Transferase capable of inactivating Cipro, also plasmid-borne.

Norfloxacin

Fluoroquinolones Levofloxacin

Effective again G- (including P. aeruginosa) and G+, specifically in treating UTI and Well tolerated, although some GI, One of the first fluoro's; least active of the prostatitis (although not systemic infection). CNS (headaches and dizziness, fluoroquinolones Drug of choice for cystic fibrosis pts suffering avoid in epileptic pts), from Pseudomonas phototoxicity and CT problems may occur (possibly avoid in Treatment of prostatitis brought on by E. coli and various STDs (but not syphilis). Urilized pregnant women or in children <18 yrs due to cartilage in wide range (skin infections, acute sinusitis, erosion). Moxi can induce exacerbation of bronchitis). Excellent activity cardiac problems (see Misc) against Pneumococcus Long half-life (once-daily pill), nonrenal clearance. should not be used in pts. at risk for arrhythmia (QT elongation) Crystalluria --> nephrotoxicity, hypersensitivity reactions that are cross-allergenic with other sulfonamides used to treat different diseases, phototoxicity, Stevens-Johnson syndrome (potentially fatal eruption of skin and mucous membrane)

Moxifloxacin

Enhanced activity against G+ (such as Strep. pneumo) and anaerobes (poor against P. aeruginosa). Only fluoro not used for UTI

Sulfonamides

Folate antagonist

Only organisms that synthesize folate de novo are sensitive. PABA (dihydrofolate Resistance can arise from precursor) analogue. plasmid transfer or random Prevents folate mutation (1) Alteration of synthesis and production synthetase to lower dependance of purine. on PABA, usually plasmid (2) decreased cell permeability (3) Enhanced production of PABA Inhibits bacterial dihydrofolic acid reductase, specifically (50,000x less inhibitor against mammallian enzyme). Also affects protozoan reductase. Synergism with Sulfa Antiprotozoal, but can be used as antibiotic. Chemically reduced by anaerobic bacteria to form reactive product.

Specific enterobacteria in urinary tract, nocardia, some protozoa, and Chlamydia trachomatis.

Stimulates growth in rickettsiae. Activity is poor against anaerobes. Excreted by kidney (lower dose in case of renal failure).

Trimethoprim & TrimethoprimSulfamethoxazole mixture

(1) Reduced cell permeability (2) Overproduction of reductase (3) Used alone for acute UTI's. Combo used for Altered reductase, typically from multiple infections, including MSSA, MRSA, Megablastic anemia, leukopenia, plasmid. Capable of spreading to pneumococcus and respiratory tract infections. granulocytopenia in Pts with AIDs multiple strains of bacteria due Agent of choice for pneumocystis and pneuocystis pneumonia to transposon element. pneumonia Resistance observed in E. coli and pneumococci Anaerobes, including bacteroides and Clostridium. Also used against vaginitis (trichomonas and bacterial) Nausea, diarrhea, stomatitis, High penetration into the peripheral neuropathy. Referred CNS. Metabolied by liver to as dilsulfuram-like reaction, (should not be given to since its similar to anti-alcholism pts. With hepatic drug, Antabuse insufficiency)

Metronidazole

--

--

Mupirocin

--

Polymyxin

--

Nitrofurantoin Urinary antiseptic Methenamine mandelate and hippurate

Point mutation in synthetase can lead to low level resistance. Pseudomonic acid Plasmid encoded tRNA (product of Pseudomonas synthetase can lead to high fluorescens). Inhibits level resistance. Resistant Staph tRNA synthetase strains seen in nosicomial infections, although 95% still susceptible Basic polypeptides that act as detergents, Ineffective against G+, proteus, disrupting bacterial and neisseria membrane and binding to endotoxin Accumulates in urinary tract to the point that it No cross-resistance with other becomes bacteriacidal. antimicrobial agents Reduces bacterial DNA to reactive form Below pH 5.5, releases formaldehyde --

Gram + cocci, including MRSA. Since its only available as a topic agent, used for skin infections

--

Inactivated after absorption, meaning only topical application

G- bacteria, particularly strains of Acinetobacter and Pseudomonas that are otherwise resistant

Extremely toxic if given systemically

Topical use only

Uncomplicated UTI that has been difficult to cure via short term therapy

Not to be used in patients with renal insufficiency. High blood levels can be toxic. Anorexia, nausea, and vomiting --

pH < 5.5 for ideal use.

G- UTI

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