A Review of Antibiotic Classes

Khaled Saad Zaghloul2014

Bacter ia by Site of InfectionMouth Peptococcus Peptostreptococcus Actinomyces

Skin/Soft Tissue S. aureus S. pyogenes S. epidermidis Pasteurella

Bone and Joint S. aureus S. epidermidis Streptococci N. gonorrhoeae Gram-negative rods

Abdomen E. coli, Proteus Klebsiella Enterococcus Bacteroides sp.

Urinary Tract E. coli, Proteus Klebsiella Enterococcus Staph saprophyticus

Upper Respiratory S. pneumoniae H. influenzae M. catarrhalis S. pyogenes

Lower Respiratory Community S. pneumoniae H. influenzae K. pneumoniae Legionella pneumophila Mycoplasma, Chlamydia

Lower Respiratory Hospital K. pneumoniae P. aeruginosa Enterobacter sp. Serratia sp. S. aureus

Meningitis S. pneumoniae N. meningitidis H. influenza Group B Strep E. coli Listeria

Beta-Lactam Structure

Discovery of penicillin

Alexander Fleming1928

Nobel Prize, 1945

β-Lactam Characteristics

Same mechanism: Inhibit cell wall synthesis Bactericidal (except against Enterococcus

sp.) Short elimination half-life Primarily renally eliminated (except

nafcillin, oxacillin, ceftriaxone, cefoperazone) Cross-allergenicity - except aztreonam

β-lactamsPharmacology

• Absorption: Variable depending on product• Distribution:

Widely distributed into tissues and fluids Pens only get into CSF in the presence of inflamed

meninges; parenteral 3rd and 4th generation cephs,meropenem, and aztreonam penetrate the CSF

• Elimination: most eliminated primarily by the kidney, dosage adj

required in the presence of renal insufficiency Nafcillin, oxacillin, ceftriaxone -eliminated by the liver ALL β-lactams have short elimination half-lives except for

a few cephalosporins (ceftriaxone)

β-LactamsAdverse Effects

• Hypersensitivity……3 to 10 %Higher incidence with parenteral

administrationMild to severe allergic reactions – rash to

anaphylaxis and deathAntibodies produced against metabolic by-

products or penicillin itselfCross-reactivity exists among all penicillins

and even other β-lactams

β-LactamsAdverse Effects

• Neurologic – especially with penicillins andcarbapenems (imipenem and meropenem)Especially in patients receiving high doses in

the presence of renal insufficiency Irritability, confusion, seizures

• Hematologic:Leucopenia, neutropenia, thrombocytopenia –

prolonged therapy (> 2 weeks)

β-LactamsAdverse Effects

• Gastrointestinal:Nausea, vomiting, diarrhea, pseudomembranous

colitis (C. difficile diarrhea)• Interstitial Nephritis:Cellular infiltration in renal tubules (Type IV

hypersensitivity reaction – characterized byabrupt increase in serum creatinine; can lead torenal failure

Especially with methicillin or nafcillin

Timeline of antibiotic resistance

• 1942 - penicillin available• 1942 - penicillin resistant S. aureus• 1940’s-1950’s - chlorampenicol, tetracycline,

erythromycin resistance• Early ‘60s - β-lactamase resistant penicillins available• Late ‘70s - MRSA arose (methicillin resistant S. aureus)• 1997 - first vancomycin resistant Enterococcus reported• July 2002 - CDC reported first case of vancomycin-

resistant S. aureus in US

Natural Penicillins(penicillin G, penicillin V)

Gram-positive Gram-negativepen-susc S. aureus Neisseria sp.pen-susc S. pneumoniaeGroup streptococci Anaerobesviridans streptococci Clostridium sp.EnterococcusOtherTreponema pallidum (syphilis)

Aminopenicillins(ampicillin, amoxicillin)

Developed to increase activity againstgram-negative aerobesGram-positive Gram-negativepen-susc S. aureus Proteus mirabilisGroup streptococci Salmonella, Shigellaviridans streptococci some E. coliEnterococcus sp. H. influenzaeListeria monocytogenes

Penicillinase-Resistant PenicillinsAntistaphylococcal Penicillins

(nafcillin, oxacillin, methicillin, cloxacillin, dicloxacillin, flucloxacillin)

Developed to overcome the penicillinaseenzyme of S. aureus which inactivatednatural penicillins

Gram-positivemethicillin-susceptible S. aureusGroup streptococciviridans streptococci

CarboxypenicillinsAntipseudomonal Penicillins

(carbenicillin, ticarcillin)Developed to further increase activityagainst resistant gram-negative aerobesGram-positive Gram-negative

marginal Proteus mirabilisSalmonella, Shigellasome E. coliH. influenzaeEnterobacter sp.Pseudomonas aeruginosa

UreidopenicillinsAntipseudomonas Penicillins(piperacillin, azlocillin, mezlocillin)

Developed to further increase activityagainst resistant gram-negative aerobesGram-positive Gram-negative viridans strep Proteus mirabilisGroup strep Salmonella, Shigellasome Enterococcus E. coli

H. influenzaeAnaerobes Enterobacter sp.Fairly good activity Pseudomonas aeruginosa

some Klebsiella sp.

β-Lactamase Inhibitor Combination(Unasyn, Augmentin, Tazosyn)

Developed to gain or enhance activity against β-lactamase producing organisms.Gram-positive Gram-negativeS. aureus H. influenzae

E. coliAnaerobes Proteus sp.Bacteroides sp. Klebsiella sp.

Neisseria gonorrhoeaeMoraxella catarrhalis

IV to PO - Penicillins

*Penicillin to Penicillin*Ampicillin to Amoxicillin*Unasyn to Augmentin

Classification and Spectrum of Activity of Cephalosporins

• Divided into 4 major groups called“Generations”

• Are divided into Generations based on: antimicrobial activity resistance to beta-lactamase

Classification of Parenteral and Oral Cephalospor ins

Cephalospor ins 1st gen 2nd gen 3rd gen 4th gen

*Parenteral Cefazolin Cefamandole Cefoperazone Cefepime

Cephalexin Cefuroxime Cefotaxime Cefpirome

Cephapirin Ceftazidime

Cephradine Ceftriaxone

*Oral Cefadroxil Cefaclor Cefdinir

Cephalexin Cefprozil Cefpodoxime

Cephradine Cefuroxime-axetil Cefixime

First Generation Cephalosporins Cefadroxil, Cephradine Cefazolin, Cephalexin

Best activity against gram-positiveaerobes, with limited activity against afew gram-negative aerobes, they arecommonly used for management of skinand soft tissue infections.

Gram-positive Gram-negativemeth-susc S. aureus E. colipen-susc S. pneumoniae K. pneumoniaeGroup streptococciViridans streptococci

Second Generation Cephalosporins

Spectrum of ActivityGram-positive Gram-negativemeth-susc S. aureus E. colipen-susc S. pneumoniae K. pneumoniaeGroup streptococci P. mirabilisviridans streptococci H. influenzae

M. catarrhalisNeisseria sp.

They are used to treat respiratory tract infections, urinary tract infections, and soft-tissue infections.

Third Generation CephalosporinsSpectrum of Activity

• In general, are even less active againstgram-positive aerobes, but have greateractivity against gram-negative aerobes

• Ceftriaxone and cefotaxime have the bestactivity against gram-positive aerobes,including pen-resistant S. pneumoniae

Third Generation CephalosporinsSpectrum of Activity

Gram-negative aerobes:E. coli, K. pneumoniae, Pr. mirabilis, H. influenzae, Mor. catarrhalis, N. gonorrhoeae (including beta-lactamase producing); N. meningitides. Pseudomonas aeruginosa (ceftazidime and cefoperazone)They are used for serious pediatric infections, including meningitis and sepsis

Fourth Generation Cephalosporins• 4th generation cephalosporins for 2 reasons:Extended spectrum of activity

gram-positives: similar to ceftriaxone gram-negatives: similar to ceftazidime, including

Pseudomonas aeruginosa; also covers beta-lactamase producing Enterobacter sp.

Stability against β-lactamases; poor inducer of extended-spectrum β -lactamases

Carbapenems(Imipenem, Meropenem)

• Most broad spectrum of activity of all antimicrobials

• Have activity against gram-positive and gram-negative aerobes and anaerobes

• Bacteria not covered by carbapenems include MRSA, VRE, coagulase-negative staph, C. difficile, Nocardia

• The 1st carbapenem approved for clinical use was imipenem-cilastatin, which has a propensity to cause seizures in children, particularly in the setting of meningitis, and therefore meropenem is more suitable for pediatric use.

MonobactamsSpectrum of Activity

Aztreonam bind preferentially to PBP 3 of gram-negative aerobes; has little to no activity against gram-positives or anaerobesGram-negativeE. coli, K. pneumoniae, P. mirabilis, S. marcescensH. influenzae, M. catarrhalisEnterobacter, Citrobacter, Providencia, MorganellaSalmonella, ShigellaPseudomonas aeruginosa

Fluoroquinolones • Novel group of synthetic antibiotics

developed in response to growing resistance• The fluor inated quinolones (FQs) represent

a major therapeutic advance: Broad spectrum of activity Excellent bioavailability, tissue penetration,

prolonged half-lives Overall safety

• Disadvantages: resistance, expense

The Available FQsOlder FQs• Norfloxacin (Noroxin®) - PO• Ciprofloxacin (Cipro®) – PO, IVNewer FQs• Levofloxacin (Tavanic®) – PO, IV• Gatifloxacin (Tequin®) – PO, IV

now discontinued• Moxifloxacin (Avelox®) – PO, IV

FQs Spectrum of Activity

Gram-positive – newer FQs with enhanced potency

• Methicillin-susceptible Staphylococcus aureus• Streptococcus pneumoniae (including PRSP)• Group and viridans streptococci – limited

activity• Enterococcus sp. – limited activity

FQs Spectrum of Activity

Gram-Negative – all FQs have excellent activity (cipro=levo>gati>moxi)• Enterobacteriaceae – including E. coli, Klebsiella

sp, Enterobacter sp, Proteus sp, Salmonella, Shigella, Serratia marcescens, etc.

• H. influenzae, M. catarrhalis, Neisseria sp.• Pseudomonas aeruginosa – significant resistance

has emerged; ciprofloxacin and levofloxacin with best activity

FQs Spectrum of Activity

Atypical Bacteria – all FQs have excellent activity against atypical bacteria including:

• Legionella pneumophila - DOC• Chlamydia sp.• Mycoplasma sp.• Ureaplasma urealyticum

Other Bacteria – Mycobacterium tuberculosis, Bacillus anthracis

FluoroquinolonesPharmacology

• Concentration-dependent bacterial killing • AbsorptionMost FQs have good bioavailability after oral

administration • DistributionExtensive tissue distribution –liver; lung; skin/soft

tissue and bone; urinary tract Minimal CSF penetration

• Elimination – renal and hepatic.

FluoroquinolonesAdverse Effects

• Gastrointestinal – 5 % Nausea, vomiting, diarrhea, dyspepsia

• Central Nervous System Headache, agitation, insomnia, dizziness, rarely,

hallucinations and seizures (elderly)• Hepatotoxicity

LFT elevation (led to withdrawal of trovafloxacin) • Phototoxicity (uncommon with current FQs)

More common with older FQs (halogen at position 8)• Cardiac

Variable prolongation in QTc interval Led to withdrawal of grepafloxacin, sparfloxacin

FluoroquinolonesAdverse Effects

• Articular Damage Arthopathy including articular cartilage damage,

arthralgias, and joint swelling Observed in toxicology studies in immature dogs Led to contraindication in pediatric patients and

pregnant or breastfeeding women Risk versus benefit Concerns of joint destruction in juvenile animals not

seen in humans• Other adverse reactions: tendon rupture,

dysglycemias, hypersensitivity

Pearls - QuinolonesCiprofloxacin: Gram-negative

Oral and parenteral fluoroquinolone with best clinical and in vitro data for activity against pseudomonas. Experience is favorable and extensive for nosocomial pneumonia, osteomyelitis, neutropenic fever, travelers diarrhea and UTIs. Now approved for treatment of pediatr ic UTIs

Other fluoroquinolones: Gram-positive(i.e levofloxacin, gatifloxacin, moxifloxacin) have

enhanced gram positive activity and are preferred for infections due to S. pneumoniae.

Dose

• Neonates: 10 mg/kg q 12 hr PO or IV.• Children: 15–30 mg/kg/24 hr divided q 12 hr

PO or IV; cystic fibrosis: 20–40 mg/kg/24 hr divided q 8–12 hr PO or IV.

• Adults: 250–750 mg q 12 hr; 200–400 mg IV q 12 hr PO (max dose: 1.5 g/24 hr

Macrolides • Erythromycin is a naturally-occurring

macrolide derived from Streptomyceserythreus – problems with acid lability,narrow spectrum, poor GI intolerance, shortelimination half-life

• Structural derivatives include clarithromycinand azithromycin: Broader spectrum of activity Improved PK properties – better bioavailability,

better tissue penetration, prolonged half-lives Improved tolerability

Macrolides

Mechanism of Action Inhibits protein synthesis by reversibly binding

to the 50S ribosomal subunit Suppression of RNA-dependent protein synthesis

Macrolides typically display bacteriostaticactivity, but may be bactericidal when present at high concentrations against very susceptible organisms

Macrolide Spectrum of Activity

Gram-Positive Aerobes – erythromycin and clarithromycin display the best activity

(Clarithro>Erythro>Azithro)• Methicillin-susceptible Staphylococcus aureus• Streptococcus pneumoniae (only PSSP) – resistance is

developing• Group and viridans streptococci• Bacillus sp., Corynebacterium sp.

Macrolide Spectrum of Activity

Gram-Negative Aerobes – newer macrolides with enhanced activity

(Azithro>Clarithro>Erythro)H. influenzae (not erythro), M. catarrhalis, Neisseria sp.DO NOT HAVE ACTIVITY AGAINST ANY ENTEROBACTERIACEAE

Macrolide Spectrum of Activity

Anaerobes – activity against upper airway anaerobesAtypical Bacteria – all macrolides have excellent

activity against atypical bacteria including:• Legionella pneumophila • Chlamydia sp.• Mycoplasma sp.• Ureaplasma urealyticum

Other Bacteria – Mycobacterium avium complex,Treponema pallidum, Campylobacter, Borrelia, Bordetella, Brucella. Pasteurella

MacrolidesPharmacology

AbsorptionErythromycin – variable absorption (15-45%);

food may decrease the absorption • Base: destroyed by gastric acid; enteric coated• Esters and ester salts: more acid stable

Clarithromycin – acid stable and well-absorbed, 55% bioavailable regardless of presence of food

Azithromycin –acid stable; 38% bioavailable; food decreases absorption of capsules

MacrolidesPharmacology

Distribution Extensive tissue and cellular distribution – clarithromycin

and azithromycin with extensive penetration Minimal CSF penetration

Elimination Clarithromycin is the only macrolide partially eliminated by

the kidney (18% of parent and all metabolites); requires dose adjustment when CrCl < 30 ml/min

Hepatically eliminated: ALL NONE of the macrolides are removed during hemodialysis! Variable elimination half-lives (1.4 hours for erythro; 3 to 7

hours for clarithro; 68 hours for azithro)

MacrolidesAdverse Effects

• Gastrointestinal – up to 33 %Nausea, vomiting, diarrhea, dyspepsiaMost common with erythro; less with new agents

• Cholestatic hepatitis - rare > 1 to 2 weeks of erythromycin estolate

• Thrombophlebitis – IV Erythro and AzithroDilution of dose; slow administration

• Other: ototoxicity (high dose erythro in patients with RI); QTc prolongation; allergy

MacrolidesDrug Interactions

Erythromycin and Clarithromycin ONLY–are inhibitors of cytochrome p450 systemin the liver; may increase concentrationsof:

Theophylline Digoxin,Carbamazepine Valproic acidCyclosporine Terfenadine, AstemizolePhenytoin WarfarinErgot alkaloids

AminoglycosidesMechanism of Action

• Multifactorial, but ultimately involvesinhibition of protein synthesis

• Irreversibly bind to 30S ribosomes– must bind to and diffuse through outer

membrane and cytoplasmic membrane and bindto the ribosome

– disrupt the initiation of protein synthesis,decreases overall protein synthesis, and producesmisreading of mRNA

• Are bactericidal

AminoglycosidesSpectrum of Activity

Gram-Positive Aerobesmost S. aureus and coagulase-negative staphviridans streptococci Enterococcus sp.

Gram-Negative Aerobes (not streptomycin)E. coli, K. pneumoniae, Proteus sp.Acinetobacter, Citrobacter, Enterobacter sp.Morganella, Providencia, Serratia, Salmonella, ShigellaPseudomonas aeruginosa (amik>tobra>gent)

Mycobacteria– tuberculosis - streptomycin– atypical - streptomycin or amikacin

AminoglycosidesPharmacology

• Absorption - poorly absorbed from GI tract• Distribution

– primarily in extracellular fluid volume; are widelydistributed into body fluids but NOT the CSF

• Elimination– eliminated unchanged by the kidney via glomerular

filtration; 85-95% of dose– elimination half-life dependent on renal function

normal renal function - 2.5 to 4 hours impaired renal function - prolonged

AminoglycosidesAdverse Effects

Nephrotoxicity– nonoliguric azotemia due to proximal tubule damage;

increase in BUN and serum Cr; reversible if caughtearly

– risk factors: long duration of therapy (> 2 weeks),underlying renal dysfunction, elderly, othernephrotoxins

Ototoxicity– 8th cranial nerve damage - vestibular and auditory

toxicity; irreversible and saturable– vestibular: dizziness, vertigo, ataxia– auditory: tinnitus, decreased hearing– risk factors: same as for nephrotoxicity

Sulfonamides• Spectrum includes: Staph, H. influenzae, Mor.

catarrhalis. Generally not effective vs. othermicrobes.

• Mechanism: acts on protein synthesis chain• Combined with erythromycin : it is as effective

as amoxcillin in treating AOM.• Sulfonamide + Trimethoprim is alternate 1st

line agent for AOM. Both drugs act on proteinchain—synergistic. Effective vs. beta-lactamase producing bacteria.

VancomycinMechanism of Action

• Inhibits bacterial cell wall synthesis at a sitedifferent than beta-lactams

• Inhibits synthesis and assembly of thesecond stage of peptidoglycan polymers

• Bactericidal (except for Enterococcus)

VancomycinSpectrum of Activity

Gram-positive bacteria– Methicillin-Susceptible AND Methicillin-Resistant S.

aureus and coagulase-negative staphylococci– Streptococcus pneumoniae (including PRSP), viridans

streptococcus, Group streptococcus– Enterococcus sp.– Corynebacterium, Bacillus. Listeria, Actinomyces– Clostridium sp. (including C. difficile), Peptococcus,

Peptostreptococcus

No activity against gram-negative aerobes or anaerobes

VancomycinPharmacology

• Absorption– absorption from GI tract is negligible after oral

administration except in patients with intense colitis– Use IV therapy for treatment of systemic infection

• Distribution– widely distributed into body tissues and fluids, including

adipose tissue.– inconsistent penetration into CSF, even with inflamed

meninges• Elimination

– primarily eliminated unchanged by the kidney viaglomerular filtration

– elimination half-life depends on renal function

VancomycinClinical Uses

• Infections due to methicillin-resistant staphincluding bacteremia, empyema, endocarditis,peritonitis, pneumonia, skin and soft tissueinfections, osteomyelitis

• Serious gram-positive infections in β-lactamallergic patients

• Infections caused by multidrug resistant bacteria.• Endocarditis or surgical prophylaxis in select

cases.• Oral vancomycin for refractory C. difficile colitis.

***DOSE:• Children: 45–60 mg/kg/24 hr divided q

8–12 hr IV;• Clostridium difficile-associated colitis;

40–50 mg/kg/24 hr divided q 6–8 hr PO.• Adults: 0.5–1 g IV q 12 hr IV.

S. aureus

Penicillin

[1950s]Penicillin-resistant

S. aureus

Evolution of Drug Resistance in S. aureus

Methicillin

[1970s]Methicillin-resistantS. aureus (MRSA)

Vancomycin-resistantenterococci (VRE)

Vancomycin

[1990s]

[1997]

Vancomycinintermediate-

resistantS. aureus(VISA)

[ 2002 ]Vancomycin-resistantS. aureus

VancomycinAdverse Effects

Red-Man Syndrome – flushing, pruritus, erythematous rash on

face and upper torso– related to RATE of intravenous infusion;

should be infused over at least 60 minutes– resolves spontaneously after

discontinuation– may lengthen infusion (over 2 to 3 hours) or

pretreat with antihistamines in some cases

VancomycinAdverse Effects

• Nephrotoxicity and Ototoxicity– rare with monotherapy, more common when

administered with other nephro- or ototoxins– risk factors include renal impairment, prolonged

therapy, high doses, ? high serumconcentrations, other toxic meds

• Dermatologic - rash• Hematologic - neutropenia and

thrombocytopenia with prolonged therapy• Thrombophlebitis

Oxazolidinones

• Linezolid (Zyvox®) is the first availableagent which received FDA approval inApril 2000; available PO and IV

• Developed in response to need for agentswith activity against resistant gram-positives (MRSA, VRE)

LinezolidMechanism of Action• Binds to the 50S ribosomal subunit near to

surface interface of 30S subunit – causes inhibition of 70S initiation complex which inhibits protein synthesis

• Bacteriostatic (cidal against some bacteria)

Linezolid Spectrum of Activity

Gram-Positive Bacteria– Methicillin-Susceptible, Methicillin-Resistant AND

Vancomycin-Resistant Staph aureus and coagulase-negative staphylococci

– Streptococcus pneumoniae (including PRSP), viridans streptococcus, Group streptococcus

– Enterococcus faecium AND faecalis (including VRE)– Bacillus. Listeria, Clostridium sp. (except C. difficile),

Peptostreptococcus, P. acnesGram-Negative Aerobes – relatively inactiveAtypical Bacteria

– Mycoplasma, Chlamydia, Legionella

Linezolid Pharmacology

• Concentration-independent bactericidalactivity

• Absorption – 100% bioavailable• Distribution – readily distributes into well-

perfused tissue; CSF penetration ≈ 70%• Elimination – both renally and nonrenally,

but primarily metabolized; t½ is 4.4 to 5.4hours; no adjustment for RI; not removed byHD

Linezolid Adverse Effects

• Gastrointestinal – nausea, vomiting, diarrhea (6 to 8 %)

• Headache – 6.5%• Thrombocytopenia – 2 to 4%

– Most often with treatment durations of > 2 weeks

– Therapy should be discontinued – platelet counts will return to normal

Clindamycin

Mechanism of Action Inhibits protein synthesis by binding

exclusively to the 50S ribosomal subunit Binds in close proximity to macrolides –

competitive inhibitionClindamycin typically displays bacteriostatic

activity, but may be bactericidal when present at high concentrations against very susceptible organisms

ClindamycinSpectrum of Activity

Gram-Positive Aerobes

• Methicillin-susceptible Staphylococcus aureus (MSSA only)

• Streptococcus pneumoniae (only PSSP) –resistance is developing

• Group and viridans streptococci

ClindamycinSpectrum of Activity

AnaerobesPeptostreptococcus some Bacteroides spActinomyces Prevotella sp.Propionibacterium FusobacteriumClostridium sp. (not C. difficile)

Other Bacteria – Toxoplasmosis gondii, Malaria

ClindamycinPharmacology

Absorption – available IV and PO Rapidly and completely absorbed (90%); food with

minimal effect on absorptionDistribution Good serum concentrations with PO or IV Good tissue penetration including bone; minimal CSF

penetration Elimination Clindamycin primarily metabolized by the liver; half-

life is 2.5 to 3 hours Clindamycin is NOT removed during hemodialysis

ClindamycinAdverse Effects

• Gastrointestinal – 3 to 4 %Nausea, vomiting, diarrhea, dyspepsia

• C. difficile colitis – one of worst offendersMild to severe diarrheaRequires treatment with metronidazole

• Hepatotoxicity - rareElevated transaminases

• Allergy - rare

Agents for Infections Due to Gram Positive Bacter iaSt

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Penicillin G

Penicillin VAnti staph penicillin: Methicillin, Oxacillin, Nafcillin

Dicloxacillin, Cloxacillin, CloxacillinVancomycin

Linezolid

Broad and Extended Spectrum PenicillinsSt

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AmpicillinAmoxicillin

Carbenicillin, Mezlocillin, Piperacillin, Ticarcillin

Ticarcillin + Clavulanic Acid = Timentin ®, Piperacillin + Tazobactam = Tazosyn®

Ampicillin + Sulbactam = Unasyn®

Amoxicillin + Clavulanic Acid = Augmentin®

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CefazolinCephalexin, Cefadroxil

Cefepime

Cefuroxime, CefoxitinCefaclor, Loracarbef, Ceftibuten

Cefprozil, Cefuroxime axetil, Cefpodoxime,

Ceftriaxone, Cefotaxime

Cefdinir CefiximeCefoperazone & Ceftazidime

1st Generation

2nd Generation

3rd Generation

4th Generation

Macrolides, Azalides and KetolidesSt

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Erythromycin

Clarithromycin, Azithromycin, Telithromycin

Broad Spectrum AntibioticsSt

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Ciprofloxacin, Levofloxacin, Moxifloxacin, Gatifloxacin

Tetracycline, Doxycycline, Minocycline

Gentamicin, Tobramycin, Netilmicin, Amikacin

Imipenem, Meropenem

Trimethoprim/Sulfamethoxazole