Chemotherapy of Bacterial Infections

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AntimicrobialsMaking sense of them

Antimicrobial Drugs

I. Terminology of chemotherapy

II. Where antimicrobial drugs come from

III. How antimicrobials work

IV. Drug resistance

V. Interactions between drugs and hosts

VI. Selecting the right antimicrobial drug

Definitions

Chemotherapy is the drug treatment for the diseases caused by bacteria and the other

pathologic microorganisms, parasites, and tumor cells.

The objective of chemotherapy is to study and to apply the drugs that have highly

selective toxicity to the pathogenic microorganisms and have no or less toxicity to the

host.

In most instances, the selective toxicity is relative, rather than absolute.

Where do antimicrobials come from?

• Fleming’s discovery of _______________

• Main sources of useful antibiotics: Streptomyces and Bacillus

(________BACTERIA____), Penicillium and Cephalosporium

(____MOLdS_____)

• Thousands have been discovered; relatively few of these are

___________.

How do they work?

• The main trick if one were to “design” an antibiotic: find something the

target pathogen has or does (e.g. a structure or pathway) which the host cell

doesn’t. For example, most bacteria have peptidoglycan while eukaryotes

don’t so a compound which destroys it or inhibits its production (like

penicillin) shouldn’t affect eukaryotes.

• Toxicity to the host is a major concern

Inhibition of cell wall synthesis

Inhibition of nucleic acid structure and function

Inhibition of protein synthesis

Interference with cell membrane structure or function

Inhibition of folic acid synthesis•Penicillins•Cephalosporins•Vancomycin•Bacitracin

•Novobiocin•Nalidixicacid

•Rifampin

•Tetracyclines•Aminoglycosides(Streptomycin,Kanamycin, Gentamicin)

•Erythromycin•Chloramphenicol

Beta-lactam antibiotics:

Penicillins

Inhibitors of beta-lactamases and combined drugs,

Cephalosporins

Monobactams

Tienamycin (carbapenems).

Sulfonamides

Quinolones

Macrolides, azalides, streptogramins, prystinamycines.

Linkozamides.

Tetracyclines.

Aminoglycosides.

Chloramphenicols.

Glycopeptides.

Cyclic polipeptides (polimixins).

Other antibiotics

ANTIBIOTICS

Dose-dependent Time-dependent

Antibacterial effect directly

depends on their

concentrations in the locus of

inflammation

(high doses 1-2 times/24h)

Aminoglycosides

Fluoroqinolones

Metronidazol

Amphotericin B

Effectiveness depends on a

period of time, during which

concentration in blood

overwhelms MIC for a

particular causative agent

(constant i.v. infusion or 3-6

times/24h)

Beta-lactames

Glycopeptides

Macrolides

Linkozamides

ANTIBIOTICS

Inhibition of Cell Wall Synthesis: b-Lactam Drugs

Irreversibly inhibit enzymes involved in the final steps of cell wall synthesisThese enzymes mediate formation of peptide bridges between adjacent stands of peptidoglycanβ-lactam ring similar in structure to normal substrate of enzyme

Drug binds to enzyme, competitively inhibit enzymatic activity

Some bacteria produce β-lactamase- enzyme that breaks the critical β-lactam ring.

β-lactam drugs include: penicillins and cephalosporins

Acid-labile.Gram+ bacteria.So, take phenoxymethylpenicillin.Large Vd, but penetration into brain: poor, except when the meningesare inflammed.Broad spectrum penicillins: amoxicillin and ampicillin are more hydrophillic and therefore, are active against gram- bacteria.

b-lactam

Inhibition of Cell Wall Synthesis

Penicillinase-resistant penicillins – Flucloxacillin

Indicated in infections caused by penicillinase-producing pen-resistant

staphlococci.

Has an isoxazolyl group at R1 sterically hinders access of the enzyme to

the β-lactam ring.

Less effective than benzylpen.

So, should be used only for pen-resistant infections.

Well-absorbed orally, but in severe infections, should be i.v. and not alone.

Staphlococci aureas-resistant strains to flucloxicillin and MRSA (methicillin-

resistant Staph aureas) – increasing problem.

Penicillins (Benzylpenicillin)

Ampicillin and amoxicillin – very active against non-β-lactamase-producing gram+

bacteria.

Because they diffuse readily into Gram- bacteria, also very active against many

strains of E. coli, H. influenzae, and Salmonella typhimurium.

Orally, amoxicillin is better because absorption is better.

Ineffective against penicillinase-producing bacteria (e.g., S. aureus, 50% of E. coli

strains, and up to 15 % of H. influenzae strains.

Many baterial β-lactamases are inhibited by clavulaic acid ± amoxicillin (co-

amoxiclav) antibiotic is effective against penicillinase-producing organisms.

Co-amoxiclav indicated in resp and UT infections, which are confirmed to be

resistant to amoxicillin.

Broad-Spectrum Penicillins

Way of

introduction

Generation of cephalosporin antibiotics

first I second II third III fourth IV

Injection Cefaloridin

Cefadroxil*

Cefazolin*

Cefalexin*

Cephradin*

Cefamandole

* Cefoxytyn*

Cefuroxime*

Cefotaxime*

Ceftriaxone*

Cefoperazone

*

Ceftazidime*

Cefpirome

*

Cefepime*

Oral Cephalexin *

Cefadroxil*

Cefuroxime

axetyl*

Cefaclor *

Cefixime *

Ceftibuten * -

Classification of Cephalosporins

Used for treatment of meningitis, pneumonia, and septicemia.

Same mech and p’col as that of penc.

May allergic rxn and cross-reactivity to pen.

Similar to pens in broad-spectrum antibacterial activity.

Cedadroxil (for UTI) in case of antibact resist.

Cefuroxime (prophylactic in surgery) – Resistant to inactivation by β-lactamases

and used in severe infections (others ineffective).

Ceftazidine – wide range of activity against gram- including Pseudomonas

aeruginosa), but is less active than cefurozime against gram+ bact (S aureus).

Used in meningitis (CNS-accessible) caused by gram- bacteria.

Cephalosporins

Not well absorbed orally.

Inhibits peptidoglycan formation.

Active against most gram+ organisms.

I.v. treatment for septicemia or endocarditis caused by

MRSA.

Used for pseudomembranous colitis (superinfection of the

bowel by Clostridium difficile – produces a toxin that

damages the colon mucosa)

Vancomycin

Antibacterial Medications that Inhibit Protein Synthesis

Target ribosomes of bacteria

Aminoglycosides: bind to 30S subunit causing it to distort and malfunction;

blocks initiation of translation

Tetracyclines: bind to 30S subunit blocking attachment of tRNA.

Macrolides: bind 50S subunit and prevents protein synthesis from continuing.

Mode of action - The amino glycosides irreversibly bind to the 16S ribosomal RNA and freeze the 30S initiation complex (30S-mRNA-tRNA) so that no further initiation can occur. They also slow down protein synthesis that has already initiated and induce misreading of the mRNA. By binding to the 16 S r-RNA the aminoglycosides increase the affinity of the A site for t-RNA regardless of the anticodon specificity. May also destabilize bacterial membranes.Spectrum of Activity -Many gram-negative and some gram-positive bacteria; Not useful for anaerobic (oxygen required for uptake of antibiotic) or intracellular bacteria.Resistance - CommonSynergy - The aminoglycosides synergize with β-lactam antibiotics. The β-lactamsinhibit cell wall synthesis and thereby increase the permeability of the aminoglycosides.

Aminoglycosides (Bactericidal)

streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin,

neomycin (topical)

Gentamicin – used for acute, life-thretening gram- infections. Has synergism

with pen and van and combo.

Amikacin – used for bact that are gent-resistant.

Netilmicin – less toxic than gentamicin.

Neomycin – too toxic for parenteral use. Used for topically for skin infections

and orally for sterilizing bowel before surgery.

Streptomycin – active against Mycobacterium tuberculosis. But bec of its

ototoxicity, rifampicin replaces.

Rifampicin – resistance develops quickly alone; so, with TB, combine with

isoniazid, ethambutol, and pyrazinamide for the 1st 2 mos of treatment, followed

by another 4 mos with rifampicin and isoniazid.

Aminoglycosides

Very safe drugs.

Ususally given orally.

Erythromycin and clarithomycin

Effective against gram- bact and can be used as an alt to pen-sensitive patients, esp in

infections caused by streptococci, staphylococci, pneumococci, and clostridia.

Don’t cross the BBB – ineffective against meningitis.

Resistance- occurs bec of plasmid-controlled Δ of their receptor on the 50S subunit.

Erythromycin – in high doses, may cause nausea and vomiting (less so with

clarithromycin and azithromycin).

Azithromycin – very long t1/2 (~40-60 hr) and a single dose is as effective in treating

chlamydial non-specific urethritis as tretracycline admin over 7 days,

Macrolides

Tetracyclines

Broad-spectrum.

Penetrate microorganisms well.

Sensitive organisms accumulate it through partly passive diffusion and partly

through active transport.

Resistant organisms develop an efflux pump and do not accumulate the drug.

Genes for tet-resistance transmitted by plasmids.

Closely assoc with those for other drugs to which the organisms will also be

resistant (e.g., sulphonamides, aminoglycosides, chloramphenicol).

Tets bind to Ca in growing bones and teeth can discolor teeth. So, should

be avoided in children < 8 yrs old.

Chloramphenicol

Broad-spectrum.

Serious side-effects: bone marrow aplasia, suppression of RBCs, WBCs,

encephalopathy, optic neuritis.

So, periodic blood counts required, esp in high doses.

Large Vd, including CNS.

Inhibits the actions of other drugs and may incr the actions of phenytoin,

sulphonlureas, and warfarin.

Neonates cannot met the drug rapidly accum ‘grey baby’ syndrome

(pallor, abdominal distension, vomiting, and collapse).

Sulfadiazine well-absorbed orally. Used to treat UTIs.

But many strains of E. coli are resistant.

So, use less toxic drugs instead.

Adverse effects: allergic rxns, skin rashes, fever.

Trimethoprin – used for UTIs and Resp TIs

Co-trimoxazole (trimethoprin + sulfamethoxazole) – used mostly for

pneumonia, neocarditis, and toxoplasmosis.

Sulphonamides

Inhibit DNA gyrase.

Nalidixic acid – used only for UTIs.

Ciprofloxin (6-fluoro substituent) that greatly enhances its effectiveness

against both gram- and gram+ bacteria.

Well-absorbed both orally and i.v.

Eliminated largely unchanged by the kidneys.

Side-effects (headache, vomiting, nausea) are rare; but convulsions may

occur.

Quinolones (GABA antagonists)

5-Nitroimidazoles

Wide-spectrum

Metronidazole – against anaerobic bacteria and protozoan infections.

Tinidazole – longer duration of action.

Diffuses into the organism where the nitro group is reduced chemically

reactive intermediates are formed that inhibit DNA synthesis and/or

damage DNA.

Antibacterial Drugs that Inhibit Nucleic Acids

Drugs that Prevent the Virus from Entering or Leaving the Host Cells

Amantadine – interferes with replication of influenza A by inhibiting the

transmembrane M2 protein that is essential for uncoating the virus.

-Has a narrow spectrum; so, flu vaccine is usually preferable.

Zanamivir – inhibits both influenza A and B neuraminadase. Decr duration

of symptoms if given within 48 hr of the onset of symptoms. Prophylactic in

healthy adults.

Immunoglobulins – Human Ig contains specific Abs against superficial Ags

of viruses can interfere with their entry into host cells. Protection against

hepA, measles, and rubellla (German measles).

Drugs that Inhibit Nucleic Acid Synthesis

Nucleoside and Nucleotide Analogs

Acyclovir- used to treat genital herpes

Cidofovir- used for treatment of cytomegaloviral infections of the eye

Lamivudine- used to treat Hepatitis B

HSV and VZV contain a thymidine kinase (TK) that acyclovir to a monophosphate

phosphorylated by host cell enzymes to acycloguanosine triphosphate, which

inhibits viral DNA pol and viral DNA synthesis.

Selectively toxic (TK of uninfected host cells activates only a little of the drug).

Viral enzymes have a much higher affinity than the host enzymes for the drug.

Effective against HSV, but does not eradicate them.

Need high doses to treat shingles.

Acyclovir

Mechanisms Responsible for Resistance to Antimicrobial Drugs Include the

Following:

1. Inactivating enzymes that destroy the drug (e.g., β-lactamases).

2. Decreased drug accumulation (e.g., tet).

3. Altering the binding sites (e.g., aminoglycosides and erythromycin).

4. Development of alternative metabolic pathways (sulphonamides (

dihydropteroate synthease) and trimethoprim (dihydrofolate reductase).

Antifungal drugs

Human fungal infections have increased dramatically

in recent years, owing mainly to advances in surgery,

cancer treatment, and critical care accompanied by

increases in the use of broad-spectrum antimicrobials

and the HIV epidemic.

Fungal infections are usually more difficult to treat

than bacterial infections, because fungal organisms grow

slowly and because fungal infections often occur in

tissues that are poorly penetrated by antimicrobial agents

(e.g., devitalized or avascular tissues). Therapy of fungal

infections usually requires prolonged treatment.

Superficial fungal infections involve cutaneous surfaces (skin, nails, and hair), and mucous membranesurfaces (oropharynx and vagina).

Deepseated or disseminated fungal infections causedby dimorphic fungi, the yeasts Cryptococcus neoformans,and various Candida spp. respond to a limited number of systemic agents: amphotericin B (a polyene), flucytosine (a pyrimidine antimetabolite), the newerazoles (ketoconazole, fluconazole, itraconazole, andvoriconazole), and caspofungin (an echinocandin).

I. Antifungals damaging permeability

of the cell membrane

•Imidazoles: Bifonazole, Clotrimazole, Econazole,

Ketoconazole, Miconazole

•Triazoles: Fluconazole, Itraconazole, Voriconazole

•Allylamines: Terbinafine, Naftifine

•Morpholines: Amorolfine

•Thiocarbamates: Tolciclate, Tolnaftate

•Substituted pyridones: Ciclopirox

•Polyene antibiotics: Amphotericin B, NystatinII. Antifungals inhibiting chitin synthesis in the cell wall

•Caspofungin, GriseofulvinIII. Antifungals inhibiting synthesis of nucleic acids

•Flucytosine

1. Polyene antibiotics

Amphotericin B and Nystatin bind to the fungal cellMembrane component ergosterol, leading to increased fungal cell membrane permeability andthe loss of intracellular constituents. Amphotericin hasa lesser affinity for the mammalian cell membranecomponent cholesterol, but this interaction does account for most adverse toxic effects.Amphotericin B has activity against Candida spp., Cryptococcus neoformans, Blastomyces dermatitidis,Histoplasma capsulatum, Sporothrix schenckii,Coccidioides immitis, Paracoccidioides braziliensis,Aspergillus spp., Penicillium marneffei, etc.

Amphotericin uses i.v. for treatment of Candida esopha-gitis, rapidly progressive mucormycosis or invasive aspergillosis. Intrathecal infusion of amphotericin B isuseful in patients with meningitis caused by Coccidioides.Intravenous administration of amphotericin B is the treatment of choice for mucormycosis and is used for theinitial treatment of cryptococcal meningitis, severe orrapidly progressing histoplasmosis, blastomycosis, and coccidioidomycosis. Intraocular injection hasbeen used successfullyfor fungal endophthalmitis.

The major acute reaction to i.v. amphotericin B is fever and chills. Tachypnea and respiratory stridoror modest hypotension also may occur. Patients withpreexisting cardiac or pulmonary disease may tolerate the metabolic demands of the reaction poorly and develop hypoxia or hypotension. Although the reaction ends spontaneously in 30 to 45 minutes, pethidine may shorten it. Pretreatment with oral paracetamol or use of i.v.hydrocortisone hemisuccinate, at the start of the

infusion decreases reactions. Azotemia occurs in80% of patients who receive amphotericinin deep mycoses.

Several lipid formulations of amphotericin B – colloidal dispersion and liposomal amphotericin B, have beendeveloped in an attempt to reduce the toxicity profileof this drug and to increase its efficacy. Formulatingamphotericin with lipids alters drug distribution, withlower levels of drug in the kidneys, reducing the incidence of nephrotoxicity. While less toxic, thelipid formulations are significantly more expensivethan conventional amphotericin B.

Polyene binds

Nystatin is a polyene antifungal drug with a ring structure and a mechanism of action similar to that of amphotericin B. Too toxic for systemic use, nystatin is limited to the topical treatment of superficial infections caused by C. albicans. Infections commonlytreated by this drug include oral candidiasis(thrush), mild esophageal candidiasis, and vaginitis.

2. Antifungal Azoles are synthetic drugs

with broad-spectrum fungistatic activity. Azoles can be

divided into two groups: the older imidazole agents(clotrimazole, ketoconazole, miconazole) in whichthe five-member azole nucleus contains two nitrogens

and the newer triazole compounds(fluconazole, itraconazole, and voriconazole), in which the azole nucleus contains three nitrogens.

All azoles exert antifungal activity by inhibitingcytochrome P450 enzymes responsible for the demethylation of lanosterol to ergosterol. Reduced fungal membrane ergosterol concen-trations result in damaged, leaky cell membranes. The toxicity of these drugs depends ontheir relative affinities for mammalian and fungalcytochrome P450 enzymes. The triazoles tend to have fewer side effects, better absorption, better drug distribution in body tissues, and fewer drug interactions.

Fluconazole does not require an acidic

environment, as does ketoconazole, for GI absorption. About 80 to 90% of an orally administereddose is absorbed, yielding high serum drug levels. Thet1/2 of the drug is 27 to 37 h, permitting once-dailydosing in patients with normal renal function. Only 11%of the circulating drug is bound to plasma proteins.The drug penetrates widely into most body tissues. Cerebrospinal fluid levels are 60 to 80% of serum levels,permitting effective treatment for fungal meningitis. About 80% of the drug is excreted unchanged in the

urine. Dosage reductions are required in the presenceof renal insufficiency.

Fluconazole is very effective in the treatment of infec-tions with most Candida spp. Thrush in the end-stageAIDS patient, often refractory to nystatin, clotrimazole,and ketoconazole, can usually be suppressed with oralfluconazole. AIDS patients with esophageal candidiasisalso usually respond to fluconazole. A single 150 mgdose has been shown to be an effective treatment forvaginal candidiasis. A 3-day course of oral fluconazole isan effective treatment for Candida urinary tract infection.Stable non-neutropenic patients with candidemiacan be adequately treated with fluconazole.

Fluconazole may be an alternative to amphotericin Bin the initial treatment of mild cryptococcalmeningitis and coccidioidal meningitis.

A significant decrease in mortality from deep-seatedmycoses was noted among bone marrow transplantrecipients treated prophylactically with fluconazole. Fluconazole taken prophylactically by end-stage AIDSpatients can reduce the incidence of cryptococcal meningitis, esophageal candidiasis, and superficial fungal infections.

Fluconazole is well tolerated. Asymptomatic liver enzymeelevation has been described, and several cases of drug associated hepatic necrosis have been reported.

Alopecia has been reported as a common adverse eventin patients receiving prolonged high-dose therapy.

Coadministration of enzyme inhibitor fluconazole withphenytoin results in increased serum phenytoin levels.

Itraconazole is lipophilic and water insoluble

and requires a low gastric pH for absorption.Oral bioavailability is variable (20 to 60%). It ishighly protein bound (99%) and is metabolizedin the liver and excreted into the bile.Itraconazole is most useful in the long-term suppressivetreatment of disseminated histoplasmosis in AIDS andin the oral treatment of nonmeningeal blastomycosis.

It is the drug of choice for all forms of sporotrichosisexcept meningitis. Itraconazole has replaced ketoconazole as the drug of choice in the treatmentof paracoccidioidomycosis and chromomycosis.

Sporo-

trichosis

Sporothrix schenkii

Ketoconazole (Nizoral®) can be absorbed orally, but it requires an acidic gastric environment.It remains useful in the treatment of cutaneous andmucous membrane dermatophyte and yeast infections,but it has been replaced by the newer triazoles in thetreatment of most serious Candida infections and disseminated mycoses. Ketoconazole is usually effective in the treatment of thrush, but fluconazoleis superior to ketoconazole for refractory thrush.Widespread dermatophyteinfections on skin surfacescan be treated easilywith oral ketoconazole. Thrush

Nausea, vomiting, and anorexia occur commonly withketoconazole when high doses are prescribed. Epigastric distress can be reduced by taking ketoconazolewith food. Pruritis and/or allergic dermatitis occurs in10% of patients. Liver enzyme elevations during therapyare usually reversible. Severe ketoconazole-associated hepatitis is rare. At high doses,ketoconazole causes a clinically significantreduction in testosterone synthesis and blocksthe adrenal response to corticotrophin. Gynecomastia,impotence, reduced sperm counts, and diminished libidocan occur in men, and prolonged drug use can resultin irregular menses in women. These hormonal effectshave led to the use of ketoconazole as a potentialadjunctive treatment for prostatic carcinoma.

Clotrimazole is a broad-spectrum fungistatic

imidazole drug used in the topical treatment of oral, skin, and vaginal infections with C. albicans. It isalso employed in the treatment of infections with cutaneous dermatophytes. Topical use results in therapeutic drug concentrations in the epidermisand mucous membranes; less than 10% of thedrug is systemically absorbed.

3. Fluorinated pyrimidinesFlucytosine (5-flucytosine, 5-FC)is an analogue of cytosine that was originallysynthesized for possible use as an antineoplasticagent. 5-FC is converted to 5-fluorouracil inside the cellby the fungal enzyme cytosine deaminase. The activemetabolite 5-fluorouracil interferes with fungal DNAsynthesis by inhibiting thymidylate synthetase.Incorporation of these metabolites into fungal RNA inhibits protein synthesis.Flucytosine has a significant antifungal activity againstCandida spp. and the fungal organisms responsiblefor chromomycosis.

4. Allylamines – reversible noncompetitive

inhibitors of the fungal enzyme squalenemonooxygenase, which converts squalene to lanosterol. With a decrease in lanosterol production, ergosterolproduction is also diminished, affecting fungal cellmembrane synthesis and function. These agents exhibit fungicidal activity against dermatophytesand fungistatic activity against yeasts.Naftifine is available for topical use only in the treat-ment of cutaneous dermatophyte and Candida infections.Terbinafine (Lamisil®) is available fortopical and systemic use (oral tablet) inthe treatment of dermatophyte skin and nail infections.

Antibiotic

Generic name/ Oral dose Dosage interval Dosage form

Brand name*

Amoxicillin 500-1 000 mg every 8 hours 250 and 500 mg Cap.

(Amoxil® generic) 1 000 mg (pneumonia) 125 and 250 mg Chew. Tab.

Amoxicillin- 250 mg - 125 mg every 8 hours 250 mg - 125 mg Tab.

clavulanate potassium 500 mg - 125 mg every 8 hours 500 mg - 125 mg Tab.

(Clavulin® or others)

875 mg - 125 mg every 12 hours 875 mg - 125 mg Tab.

Azithromycin 500 mg DIE day 1 every 24 hours 250 mg Tab.

(Zithromax® or others) then 250 mg DIE x 4 days

Cefadroxil 1 000-2 000 mg/jour every 12 or 24 hours 500 mg Cap.

(Duricef® generic) (urinary tract infections)

1 000 mg/day (pharyngitis)

Cefprozil 250-500 mg every 12 hours 250 and 500 mg Tab.

(Cefzil® or others) 500 mg (urinary tract infections) every 24 hours

Cefuroxime axetil 250-500 mg every 12 hours 250 and 500 mg Tab.

(Ceftin® or others)

Cephalexin 500-1 000 mg every 6 or 12 hours 250 and 500 mg Cap. or Tab.

(Keflex® generic)

Ciprofloxacin 250-750 mg every 12 hours 250, 500 and 750 mg Tab.

(Cipro® or others)

Ciprofloxacin XL 500-1 000 mg every 24 hours 500 and 1 000 mg Tab.

(Cipro XL®) (urinary tract infections)

Clarithromycin 250 mg (pharyngitis) every 12 hours 250 mg Tab.

(Biaxin Bid® or others) 500 mg (bronchitis, pneumonia, every 12 hours 500 mg Tab.

sinusitis)

(Biaxin XL®) 1 000 mg (bronchitis, pneumonia, every 24 hours 500 mg Tab.

sinusitis, pharyngitis)

Clindamycin 150-450 mg every 6 hours 150 and 300 mg Cap.

(Dalacin C® or others)

Doxycyclin 100 mg (bronchitis, pneumonia) every 12 hours 100 mg Cap. or Tab.

(Vibra-Tabs® or others)

Levofloxacin 250-750 mg every 24 hours 250, 500 and 750 mg Tab.

(Levaquin® or other)

DOSAGE GUIDELINES COMMONLY USED IN ADULTS

Antibiotic

Generic name/ Oral dose Dosage interval Dosage form

Brand name*

Metronidazole 250 mg every 6 hours 250 mg Tab.

(Flagyl® generic)

500 mg every 8 hours

Moxifloxacin 400 mg every 24 hours 400 mg Tab.

(Avelox®)

Nitrofurantoin 100 mg every 12 hours 100 mg Cap.

(MacroBid®)

(Macrodantin® generic) 50-100 mg every 6 hours 50 and 100 mg Cap.

Norfloxacin 400 mg every 12 hours 400 mg Tab.

(Generic)

Ofloxacin 200 mg every 12 hours 200, 300 and 400 mg Tab.

(Generic)

Penicillin V 300 mg every 6 hours 300 mg Tab.

(Pen-Vee® generic) 600 mg

(pharyngitis) every 12 hours

Trimethoprim- 160 mg - 800 mg every 12 hours 160 mg - 800 mg Tab.

sulfamethoxazole

(Septra DS® generic)

Trimethoprim 100-200 mg every 12 or 24 hours 100 and 200 mg Tab.

(Generic)

Vancomycin 125-500 mg every 6 hours 125 and 250 mg Cap.

(Vancocin®)

DOSAGE GUIDELINES COMMONLY USED IN ADULTS