PENICILLINSCEPHALOSPORINSFLUOROQUINOLONESAMINOGLYCOSIDESMONOBACTAMSCARBAPENEMSMACROLIDESOTHER

NatrualFirst generationCiprofloxacin (Cipro)Levofloxacin (Levaguin)Moxifloxacin (Avelox)NorfloxacinAmikacinGentamicinKanamycinNeomycinTobramycinAztreonamErtapenemImienemMeropenemAzithromycinClarithromycinDirithromycinErythromycinClindamycinVancomycinRifampinDoxycyclineLinezolidTetracyclineTrimethoprim/ sulfamethoxacole

Penicillin GPenicillin-VKCephalothinCefazolin (Ancef, Kefzol)CephapririnCephalexin (Keflex)other

Penicillinase ResistantSecond Generation

MethicillinNafcillinOxacillinotherCefacorCefotetan (Cefotan)other

AminopenicillinsThird Generation

AmpicillinCeftriaxone (Rocephin)other

Fourth Generation

CefpiromeCefepime

Antibiotic Grouping By Mechanism

Cell Wall SynthesisPenicillinsCephalosporinsVancomycinBeta-lactamase InhibitorsCarbapenemsAztreonamPolymycinBacitracin

Protein Synthesis InhibitorsInhibit 30s SubunitAminoglycosides (gentamicin)TetracyclinesInhibit 50s SubunitMacrolidesChloramphenicolClindamycinLinezolidStreptogramins

DNA Synthesis InhibitorsFluoroquinolonesMetronidazole

RNA synthesis InhibitorsRifampin

Mycolic Acid synthesis inhibitorsIsoniazid

Folic Acid synthesis inhibitorsSulfonamidesTrimethoprim

Antibiotic Classification & Indications

Inhibits Cell Wall Synthesis

Penicillins(bactericidal: blocks cross linkingvia competitive inhibition of the transpeptidase enzyme)

Class/MechanismDrugsIndications (**Drug of Choice)Toxicity

PenicillinPenicillin GAqueous penicillin GProcaine penicillin GBenzathine penicillin GPenicillin VStrep. pyogenes (Grp.A)**Step. agalactiae (Grp.B)**C. perfringens(Bacilli)**Hypersensitivity reactionHemolytic anemia

AminopenicillinsAmpicillinAmoxicillinAbove + Gram-negative:E. faecalis**E. Coli**Above

Penicillinase-resistant-penicillinsMethicillinNafcillinOxacillinCloxacillinDicloxacillinAbove +PCNase-producingStaph. aureusAbove +Interstitial nephritis

Antipseudomonal penicillinsCarbenicillinTicarcillinPiperacillinAbove +Pseudomonas aeruginosa**Above

Cephalosporins(bactericidal: inhibits bacterial cell wall synthesis via competitive inhibition of the transpeptidase enzyme)

1st generationCefazolinCephalexinStaph. aureus**Staph. epidermidis**Some Gram-negatives:E. ColiKlebsiellaAllergic reactionCoombs-positive anemia (3%)

2nd generationCefoxitinCefaclorCefuroximeAbove +Gram-negativeAllergic ReactionETOH Disulfiram reaction

3rd generationCeftriaxoneCefotaximeCeftazidimeCefepime (4th generation)Above +Gram-negativePseudomonasAllergic ReactionETOH Disulfiram reaction

Other Cell Wall Inhibitors

Vancomycin(bactericidal: disrupts peptioglycan cross-linkage)VancomycinMRSA**PCN/Ceph allegies**S. aureusS. epidermidisRed man syndromeNephrotoxicityOtotoxicity

Beta-lactamase Inhibitors(bactericidal: blocking cross linking)Clavulanic AcidSulbactamTazobactamS aureus**S epidermis**E.Coli**Klebsiella**Hypersensitivity ReactionHemolytic anemia

CarbapenemsImipenem (+ cilastatin)MeropenemDoripenemErtapenemBroadest activity of any antibiotic(except MRSA, Mycoplasma)

AztreonamAztreonamGram-negative rodsAerobesHospital-acquired infections

PolymyxinsPolymyxin BPolymyxin ETopical Gram-negative infections

BacitracinBacitracinTopical Gram-positive infections

Protein Synthesis Inhibition

Anti-30S ribosomal subunit

Aminoglycosides(bactericidal: irreversible binding to 30S)GentamicinNeomycinAmikacinTobramycinStreptomycinAerobic Gram-negativesEnterobacteriaceaePseudomonasNephrotoxicityOtotoxicity

Tetracyclines(bacteriostatic: blocks tRNA)TetracyclineDoxycyclineMinocyclineDemeclocyclineRickettsiaMycoplasmaSpirochetes(Lyme's disease)HepatotoxicityTooth discoloration Impaired growthAvoid in children < 12 years of age

Anti-50S ribosomal subunit

Macrolides(bacteriostatic: reversibly binds 50S)ErythromycinAzithromycinClarithromycinStreptococcusH. influenzaeMycoplamsa pneumoniaCoumadin Interaction (cytochrome P450)

Chloramphenicol(bacteriostatic)ChloramphenicolH influenzaeBacterial MeningitisBrain abscesAplastic AnemiaGray Baby Syndrome

Lincosamide(bacteriostatic: inhibits peptidyl transferase by interfering with amino acyl-tRNA complex)ClindamycinBacteroides fragilisS aureusCoagulase-negative Staph & StrepExcellent Bone PenetrationPseudomembranous colitisHypersensitivity Reaction

Linezolid(variable)LinezolidResistant Gram-positives

StreptograminsQuinupristinDalfopristinVREGAS and S. aureus skin infections

DNA Synthesis Inhibitors

Fluoroquinolones(bactericidal: inhibit DNA gyrase enzyme, inhibiting DNA synthesis)

1st generationNalidixic acidSteptococcusMycoplasmaAerobic Gram +PhototoxicityAchilles tendon ruptureImpaired fracture healing

2nd generationCiprofloxacinNorfloxacinEnoxacinOfloxacinLevofloxacinAs Above +Pseudomonasas above

3rd generationGatifloxacinAs above + Gram-positivesas above

4th generationMoxifloxacinGemifloxacinAs above + Gram-positives + anaerobesas above

Other DNA Inhibitors

Metronidazole(bacteridical: metabolic biproducts disrupt DNA)Metronidazole (Flagyl)AnaerobicsSeizuresCrebelar dysfunctionETOHdisulfram reaction

RNA Synthesis Inhibitors

Rifampin(bactericidal: inhibits RNA transcription by inhibiting RNA polymerase)RifampinStaphylococcusMycobacterium(TB)Body fluid discolorationHepatoxicity (with INH)

Mycolic Acids Synthesis Inhibitors

IsoniazidIsoniazidzTBLatent TB

Folic acid SynthesisInhibitors

Trimethoprim/Sulfonamides(bacteriostatic: inhibition with PABA)Trimethoprim/Sulfamethoxazole (SMX)SulfisoxazoleSulfadiazineUTI organismsProteusEnterobacterThrombocytopeniaAvoid in third trimester of pregnancy

PyrimethaminePyrimethamineMalariaT. gondii

Bacteria Overview

Gram Postive Cocci

StaphylococcusStaph. aureusMSSAMRSAStaph. epidermisStaph saprophyticus

StreptococcusStrep pneumoniaeStrep pyogenes (Group A)Strep agalacticae (Group B)Strep viridansStrep Bovis (Group D)

EnterococciE. faecalis (Group D strep)

Gram Positive Bacilli

Spore FormingBacillus anthracisBacillus cereusClostridium tetaniClostridium botulinumClostridium perfringensClostridium difficile

Non-Spore FormingCorynebacterium diphtheriaeListeria monocytogenes

Gram Negative Cocci

NeisseriaNeisseria meningitidisNeisseria gonorrhoeae

Gram Negative Bacilli

EntericsEscherichia coliSalmonella typhiSalmonella enteridisShigella dysenteriaeKlebsiella pneumoniaeSerratiaProteusCampylobacter jejuniVibrio choleraeVibrio parahaemolyticus/vulnificusHelicobacter pyloriPseudomonas aeruginosaBacteroides fragilis

Respiratory bacilliHaemophilus influenzaeHaemophilius ducreyiBordatella pertussis

Zoonotic bacilliYersinia enterocoliticaYersinia pestisBrucellaFrancisella tularensisPasteurella multocidaBartonella henselae

OtherGardnerella vaginalis

Other Bacteria

MycobacteriaMycobacterium tuberculosisMycobacterium lepraeMOTTS

SpirochetesBorrelia burgdorferiLeptospira interrogansTreponema pallidum

ChlamydiaceaeChlamydia trachomatisChlamydophilaRickettsiaEhrlichia

MycoplasmataceaeMycoplasma pneumoniaeUreaplasma urealyticum

Fungus-like BacteriaActinomyces israeliiNocardia

Antibiotic Resistance Mechanisms

Bacteria develop ability to hydrolyze these drugs using lactamase confers resistance to penicillin e.g. E. coli, Staph epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae add lactamase inhibitore.g. clavulanic acid in amoxicillin-clavulanate (Augmentin) Genetic mutation ofmecA a bacterial gene encoding a penicillin-binding protein. New PBP has reduced affinity for antibiotics confers resistance to methicillin, oxacillin, nafcillin e.g. MRSA Altered cell wall permeability confers resistance to tetracyclines, quinolones, trimethoprim and lactam antibiotics Creation of biofilm barrier provides an environment where offending bacteria can multiply safe from the hoste immune system Salmonella Staph epidermidis Active efflux pumps confers resistance to erythromycin and tetracycline e.g. msrA gene in Staph Alteredpeptidoglycansubunit (alteredD-alanyl-D-alanine ofNAM/NAG-peptide) confers resistance to vancomycin e.g. vancomycin resistant enterococcus (VRE) Ribosome alteration erm gene confer inducible resistance to MLS (macrolide lincosamide streptogranin) agents via methylation of 23s rRNA demonstrate usingD zone test for inducible clindamycin resistance in Staph and beta hemolytic Strep

Penicillins

Mechanism interfer with bacterial cell wall synthesis Subclassification and tested examples natural penicillin G penicillinase-resistant methicillin (Staphcillin) aminopenicillins ampicillin (Omnipen, Polycillin)

Cephalosporins

Overview bactericidal Mechanism disrupts the synthesis of thepeptidoglycanlayer of bacterialcell walls does so through competitive inhibition on PCB (penicllin binding proteins) peptidoglycan layer is important for cell wall structural integrity. same mechanicsm of action asbeta-lactam antibiotics(such aspenicillins) Subclassification and tested examples first generation cefazolin (Ancef, Kefzol) second generation cefaclor (Ceclor) third generation cefriazone (Rocephin) fourth generation cefepime (Maxipime)

Fluoroquinolones

Mechanism blocks DNA replication via inhibition of DNA gyrase Side effects inhibit early fracture healingthrough toxic effects on chondrocytes increased rates oftendinitis, with special predilection for the Achilles tendon. tenocytes in the Achilles tendon have exhibited degenerative changes when viewed microscopically after fluoroquinolone administration. recent clinical studies have shown an increased relative risk of Achilles tendon rupture of 3.7. Subclassification and tested examples ciprofloxacin (Cipro) levofloxacin (Levaquin)

Aminoglycosides

Mechanism bactericidal inhibition of bacterial protein synthesis work bybinding to the 30s ribosome subunit, leading to the misreading of mRNA. This misreading results in the synthesis of abnormal peptides that accumulate intracellularly and eventually lead to cell death. These antibiotics arebactericidal. Subclassification and tested examples gentamicin (Garamycin)

Vancomycin

Coverage gram-positivebacteria Mechanism bactericidal an inhibitor of cell wall synthesis Resistance increasing emergence of vancomycin-resistantenterococcihas resulted in the development of guidelines for use by the(CDC) indications for vancomycin serious allergies to penicillins orbeta-lactam antimicrobials serious infections caused by susceptible organisms resistant topenicillins (MRSA, MRSE) surgical prophylaxis for major procedures involving implantation ofprosthesesin institutions with a high rate of MRSA or MRSE

Rifampin

Most effective against intracellular phagocytized Staphylococcus aureus in macrophages

Linezolid

Linezolid binds to the23Sportion of the 50S subunit andacts by preventing the formation of theinitiation complexbetween thethe30Sand50Ssubunits of the ribosome.

Splenectomy

Splenectomy patients or patients with functional hyposplenism require the following vaccines and/or antibiotics Pneumococcal immunization Haemophilus influenza type B vaccine Meningococcal group C conjugate vaccine Influenza immunization Lifelong prophylactic antibiotics (oral phenoxymethylpenicillin or erythromycin)

Systemic Adverse Effects of Common Antibiotics and ClassesAntibiotic ClassAntibiotic Class MembersMost Common Side EffectsAdditional Clinical Comments

Penicillinspenicillin, amoxicillin, amoxicillin-clavulanate, ampicillin, piperacillin-tazobactam, nafcillin, oxacillinrash, diarrhea, abdominal pain, nausea/vomiting, drug fever, hypersensitivity (allergic) reactionsif bloody stools, anaphylaxis, severe skin reaction, fever occur contact health care provider immediately; ampicillin may cause pseudomembranous colitis

Cephalosporinscephalexin, cefaclor, cefuroxime, ceftibuten, cefdinir, cefixime, ceftriaxonerash, diarrhea, nausea/vomiting (rare), hypersensitivity (allergic) reactions, serum sickness, vaginal candidiasiscross-hypersensitivity may occur in patients with documented penicillin allergy

Aminoglycosidesgentamicin, tobramycin, amikacinrenal (kidney) toxicity, ototoxicity (hearing loss), dizziness, nausea/vomiting, nystagmuslonger or multiple treatment periods may lead to greater risk for ototoxicity, renal (kidney) toxicity

Carbapenemsmeropenem, ertapenem, doripenem, imipenem-cilastatindiarrhea, nausea/vomiting, headache, rash, liver toxicity, eosinophilia (elevated white blood cells)Hypersensitivity reactions reported with meropenem, imipenem in patients with penicillin allergy

AntituberculosisAgentsrifampin, rifabutin, isoniazid, pyrazinamide, ethambutol, dapsonediarrhea, nausea/vomiting, anorexia, hemolytic anemia, liver toxicity, headache, peripheral neuropathy, dizziness, reddish-orange body fluids (rifampin, rifabutin only)sides effects vary among agents, check individually; vitamin B6 (pyridoxine) may be taken to help prevent peripheral neuropathy with isoniazid

Glycopeptidesvancomycin, telavancinvancomycin: red man syndrome (flushing, hypotension, itching); phlebitis; telavancin: taste alteration, nausea/vomiting, headache, dizzinessIV infusion of vancomycin over 60 minutes may prevent red man syndrome

Macrolideserythromycin, azithromycin, clarithromycinabdominal pain, diarrhea, anorexia, nausea/vomiting, taste alterations (clarithromycin)high rate of gastrointestinal side effects; do not crush, chew, break, open enteric-coated or delayed-release pill

Sulfonamidestrimethoprin-sulfamethoxazole, erythromycin-sulfisoxazole, sulfadiazinenausea/vomiting, diarrhea, anorexia, abdominal pain, rash, photosensitivity, headache, dizzinessAvoid prolonged sunlight exposure; use sunscreen, wear protective clothing; antibiotic cause of Stevens Johnson Syndrome, Toxic Epidermal Necrolysis

Tetracyclinestetracycline, doxycycline, minocyclinenausea/vomiting, diarrhea, anorexia, abdominal pain, tooth discoloration in children < 8 years, liver toxicityAvoid prolonged sunlight exposure; use sunscreen, wear protective clothing

Quinolonesciprofloxacin (Cipro), levofloxacin (Levaquin), moxifloxacin (Avelox), ofloxacin (Floxin)nausea/vomiting, diarrhea, abdominal pain, headache, lethargy, insomnia, photosensitivity (can be severe)Avoid prolonged sunlight exposure; use sunscreen, wear protective clothing;moxifloxacin associated with higher rates of side effects [shehab]; tendon rupture (rare) more common in age > 60, with corticosteroid use, in kidney, heart, lung translant recipients

Lincosamideclindamycin, lincomycinpseudomembranous colitis (may be severe), diarrhea, nausea/vomiting, rash, hypersensitivity, jaundice (clindamycin)if severe diarrhea during treatment or for up to 8 weeks after treatment consult health care provider immediately, may be pseudomembranous colitis (C. dificile); consider use of less toxic agents

Miscellaneousmetronidazolenausea/vomiting, dizziness, headache, vaginal candidiasis, metallic tasteavoid alcohol use during treatment and for up to 3 days after, combined use may lead to cramps, nausea/vomiting, flushing, headache; may discolor urine red-brown

In a 2008 study, antibiotic side effects led to greater than 140,000 emergency department admissions per year in the United States. Roughly 50 percent of emergency visits were due to reactions to antibiotics in the penicillin class of drugs, and the other 50 percent were due to a wide variety of antibiotics used to treat many different types of infections. In this study, children less than one year of age were found to have the highest rate of antibiotic side effects. Allergic reactions accounted for the most common type of side effect. It was estimated that over 142,000 emergency department visits per year were due to antibiotic adverse events, and approximately four-fifths of these events were due to allergic reactions. Allergic reactions can typically only be prevented by avoiding the drug, although desensitization may be possible in certain circumstances for patients who have no other antibiotic options.1There are also several side effects that are common to most antibiotics, regardless of class or drug. These side effects may include antibiotic-associated diarrhea, yeast infections, serious allergic skin reactions, and complications from intravenous use of antibiotics. Antibiotic-associated diarrhea- Antibiotic-associated diarrhea occurs in patients receiving antibiotics and occurs for no explainable reason. Five to twenty-five percent of patients may develop antibiotic-associated diarrhea. The diarrhea occurs due to eradication of the normal gut flora by the antibiotic and results in an overgrowth of infectious bacteria, such as Clostridium dificile. If the diarrhea is severe, bloody, or is accompanied by stomach cramps of vomiting, a physician should be contacted. The most common antibiotics implicated in antibiotic-associated diarrhea are amoxicillin-clavulanate, ampicillin, and cefixime; however, other antibiotics may lead to this side effect, including cephalosporins, fluoroquinolones, azithromycin, clarithromycin, erythromycin, and tetracycline.2 Vaginal yeast infections or oral thrush (candida species):Antibiotics may also change the normal flora balance in the vagina, often leading to an overgrowth of fungal species. Candida albicans is a common fungus normally present in small amounts in the vagina, mouth, gastrointestinal tract, and on the skin and does not normally cause disease or symptoms. However, the fungus may take over when there is limited competition from bacteria due to antibiotic treatment. Stevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN):Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious allergic reactions to substances, often drugs, that result in serious skin and mucous membrane disorders. Antibiotics such as sulfonamides, penicillins, cephalosporins, and fluoroquinolones may result in SJS and TEN. SJS and TEN can both cause rash, skin peeling, and sores on the mucous membranes and may be life-threatening.3 Injection site reactions and phlebitis:A reaction to an antibiotic can occur if the antibiotic is given intravenously in a vein. Injections site reactions and phlebitis (vein inflammation) can occur with intravenously (IV) administered antibiotics. The vein and area with the IV needle may be red, swollen and hot. An infection may or may not be present. Typically, the needle must be removed and reinserted elsewhere to help clear the injection site reaction.