pharmacology- antibiotics assist.prof.dr. hussam a-humadi · 2018-08-31 · pharmacology-...

Pharmacology- Antibiotics Assist.Prof.Dr. Hussam A-Humadi

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Antimicrobial Drugs

• Empiric AB antimicrobial therapy should be initiated based on expected pathogens for a given

infection.

• Resistance is increasing among many pathogens (a review of institutional, local, regional,

national, global susceptibility trends) Development of empiric therapy regimens.

• Accurate allergy hx

• Pregnancy/ Lactation

• Culture and sensitivity

• Switching from parenteral to oral therapy

• where possible (Many oral agents have

• excellent bioavailability

• Drug interactions

• Renal or Hepatic insufficiency, or both

A- Antibacterial Agents:

1. Penicillins

2. Cephalosporins

3. Monobactams

4. Carbapenems

5. Aminoglycosides

6. Vancomycin

7. Fluoroquinolones

8. Macrolide and Lincosamide Antibiotics

9. Sulfonamides and Trimethoprim

10. Tetracyclines

B- Antimicrobial Agents, Miscellaneous

C- Antimycobacterial Agents


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D- Antiviral Agents

E- Antifungal Agents

A-Antibacterial

Penicillins (PCNs)

• Irreversibly bind PCN-binding proteins in the bacterial cell wall, causing osmotic rupture &

death.

• Diminished role today because of acquired resistance in many bacterial species through

alterations in PCN-binding proteins or expression of hydrolytic enzymes.

• PCNs Remain among the drugs of choice for Syphilis; group A streptococci, Listeria

monocytogenes, Pasteurella multocida, Actinomyces, some anaerobic infections.

Antibiotics that inhibit cell wall synthesis

1. Cycloserine

2. Bacitracin

3. Vancomycin

4. B- lactam

• Pencillins

• Cephalosporines

• Carbenems

• Aztreonam


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PCNs Treatment:

• Aqueous penicillin G: IV preparation of PCN and the drug of choice for most penicillin-

susceptible streptococcal infections & neurosyphilis.

• Procaine penicillin G: IM repository form of penicillin G that can be used as an alternative

treatment for neurosyphilis in combination with probenecid,

• Benzathine PCN

LA IM repository form of penicillin G commonly used for treating early latent syphilis (<1

year duration and late latent syphilis (unknown duration or >1 year IM weekly for three

doses]).

Occasionally given for group A streptococcal pharyngitis & prophylaxis after acute rheumatic

fever.

• Penicillin V: Oral formulation of PCN that is typically used to treat group A streptococcal

pharyngitis.(rheumatic fever protection)

• Ampicillin:, Drug of choice for treatment of : infections caused by susceptible enterococcus

species, or L. monocytogenes.

Penicillin

Narrow spectrum Wide spectrum Natural

• Penicillin G

• Penicillin V

V v v v narrow spect.

• Methicillin

• Cloxacillin

• Nafcillin

• Dicloxaciilin

• Flucloxacillin


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Oral ampicillin (250-500 mg PO q6h) may be used for uncomplicated sinusitis, pharyngitis, otitis

media, and urinary tract infections (UTIs), but amoxicillin is generally preferred.

• Ampicillin/sulbactam

combines ampicillin with the B-lactamase inhibitor sulbactam, thereby extending its

spectrum to include methicillin-sensitive Staphylococcus aureus (MSSA), anaerobes, and many

Enterobacteriaceae.

The sulbactam component also has unique activity against some strains of Acinetobacter.

The agent is effective for infections of URT & LRT, GUT, and abdominal, pelvic, and

polymicrobial soft tissue infections, including those due to human or animal bites.

• Amoxicillin:, Oral antibiotic similar to ampicillin that is commonly used for :uncomplicated

sinusitis, pharyngitis, otitis media, community-acquired pneumonia & UTIs.

• Amoxicillin/clavulanic acid

Oral antibiotic similar to ampicillin/sulbactam that combines amoxicillin with the B-

lactamase inhibitor clavulanate. It is useful for treating : complicated sinusitis & otitis media

& for prophylaxis of human or animal bites after appropriate local treatment.

• Nafcillin and Oxacillin:, penicillinase-resistant synthetic PCNs that are the drugs of choice for

treating : MSSA infections. Dose reduction should be considered in decompensated liver

disease.

• Dicloxacillin :. Oral antibiotic with a spectrum of activity similar to that of Nafcillin and Oxacillin,

that are typically used to treat localized skin infections.

• Piperacillin: Extended-spectrum PCN with enhanced G -ve activity as well as enterococcal

activity. Has reasonable antipseudomonal activity but generally requires co-administration of an

Aminoglycoside for treatment of serious infections.

• Ticarcillin/clavulanic acid: combines Ticarcillin with the B-lactamase inhibitor Clavulanic acid.

Extends the spectrum to include most Enterobacteriaceae, MSSA, & anaerobes, making it

useful for intra-abdominal & complicated soft tissue infections.

Unique role in treatment of Stenotrophomonas infections.

Has a high Na content & should be used cautiously in patients at risk for fluid overload.

• Piperacillin/tazobactam

for Pseudomonas

Combines piperacillin with the B-lactamase inhibitor tazobactam.


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Similar spectrum & indications as Ticarcillin/Clavulanic acid but enhanced has activity

against Ampicillin-sensitive enterococci.

Addition of an Amg should be considered for treatment of serious infections caused by

Pseudomonas aeruginosa or for nosocomial pneumonia.

• All PCNs derivatives

1. Rarely associated with anaphylaxis, interstitial nephritis, anemia, leukopenia.

2. Prolonged high-dose therapy (>2 weeks) is typically monitored with weekly serum

creatinine and complete blood cell counts.

3. LFTs are also monitored with oxacillin/nafcillin as these agents can cause hepatitis.

Ticarcillin/clavulanic acid can aggravate bleeding by interfering with platelet adenosine

diphosphate receptors.

All patients should be asked about PCN, cephalosporin, or carbapenem allergy.

These agents should not be used in patients with a reported serious PCN allergy without prior

skin testing or desensitization, or both.

Cephalosporins

• Exert their bactericidal effect by interfering with cell wall synthesis by the same mechanism as PCNs.

• Clinically useful (low toxicity + broad spectrum).

• All currently available 1st-4th-generation cephalosporins devoid of activity against enterococci & methicillin-resistant S. aureus ( MRSA ).

Treatment

a) 1st-Generation Cephalosporins: have activity against staphylococci, streptococci, and some

Escherichia coli, Klebsiella, and Proteus species. Limited activity against other enteric G─ ve

bacilli and anaerobes.

1) Cefazolin IV/IM q8h is the most commonly used parenteral preparation,

2) Cephalexin

3) Cefadroxil

• The above two agents are oral preparations. These limited-activity agents are commonly used

for treating skin/soft tissue infections, UTIs, minor MSSA infections, and for surgical prophylaxis

(Cefazolin).


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b) 2nd - Generation Cephalosporins: Expanded coverage against enteric G─ rods. Divided into

above& below-the-diaphragm agents.

1) Cefuroxime: IV/IM q8h. Useful for treatment of infections above the diaphragm.

Has reasonable antistaphylococcal + antistreptococcal activity.

Has an extended spectrum against G ▬ ve aerobes

Used for skin/soft tissue infections, complicated UTIs, some community-acquired RTIs.

Does not reliably cover Bacteroides fragilis.

2) Cefuroxime axetil :

3) Cefprozil:

4) Cefaclor :

All are oral 2nd -generation cephalosporins typically used for bronchitis, sinusitis, otitis media,

UTIs, local soft tissue infections, oral step-down therapy for pneumonia or cellulitis responsive

to parenteral cephalosporins.

5) Cefoxitin :

6) Cefotetan

• Above two are useful for treatment of infections below the diaphragm.

• Have reasonable activity against G ▬ ve , aerobes, including B. fragilis, and are commonly used

for intra-abdominal or gynecologic surgical prophylaxis & infections, (diverticulitis & pelvic

inflammatory disease).

c) 3rd -Generation Cephalosporins

Broad coverage against aerobic G ▬ ve bacilli

Retain sig activity against streptococci + MSSA.

Have moderate anaerobic activity but generally not against B. fragilis.

1) Ceftazidime : only 3rd generation that is useful for treating serious P. aeruginosa infections. Some of these agents have substantial central nervous system (CNS) penetration and are useful in treating meningitis

Not reliable for the treatment of serious infections caused by organisms producing AmpC B-

lactamases regardless of the results of susceptibility testing.

These pathogens should be treated empirically with carbapenems, cefepime, or

fluoroquinolones.

2) Ceftriaxone: 3) Cefotaxime:, very similar to one another in spectrum and efficacy. Used as empiric therapy for pyelonephritis, urosepsis, pneumonia, intra-abdominal infections

(combined with metronidazole), gonorrhea, meningitis.

Also used for osteomyelitis, septic arthritis, endocarditis, soft tissue infections caused by

susceptible organisms.

4) Cefpodoxime proxetil : 5) Cefdinir : 6) Ceftibuten :


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7) Cefditoren pivoxil:, are oral useful for the treatment of bronchitis + complicated sinusitis, otitis media, and UTIs. These agents can also be used as step-down therapy for community-acquired pneumonia.

8) Cefpodoxime : single-dose Rx for uncomplicated gonorrhea. 9) Ceftazidime: IV/IM q8h, may be used for treatment of infections caused by susceptible

strains of P. aeruginosa.

d) 4th -Generation Cephalosporin

1) Cefepime

Has excellent aerobic G ▬ ve coverage, (P. aeruginosa + other bacteria producing AmpC B-lactamases).

Its G + ve activity is similar to that of the ceftriaxone and cefotaxime.

Cefepime is routinely used for empiric therapy in febrile neutropenic patients.

Has a prominent role in treating infections caused by antibiotic-resistant G ▬ ve bacteria and some infections involving both G ▬ ve & G + ve aerobes in most sites,

although clinical experience for treatment of meningitis is more limited. Anti-anaerobic coverage should be added where anaerobes are suspected.

All cephalosporins have been rarely associated with anaphylaxis, interstitial nephritis, anemia, and leukopenia.

PCN-allergic patients have a 5-10% incidence of a cross-hypersensitivity reaction to cephalosporins.

Should not be used in a patient with a reported severe PCN allergy (i.e., anaphylaxis, hives) without prior skin testing or desensitization, or both.

Prolonged therapy (>2 weeks) is typically monitored with a weekly s. creatinine & CBC.

Ceftriaxone can cause biliary sludging requiring discontinuation of the medication.

Monobactams

Aztreonam

• inhalation 3Xdaily

• Monobactam that is active only against aerobic G ▬ ve bacteria, including P. aeruginosa.

• Useful in known B-lactam allergy, as no apparent cross-reactivity is present.

• An inhalation formulation is now available to improve respiratory symptoms in patients with Pseudomonas aeruginosa infection.


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Carbapenems

Imipenem:

Meropenem:

Doripenem :,

Ertapenem : are the currently available Carbapenems.

• Exert their bactericidal effect by interfering with cell wall synthesis, similar to PCNs and cephalosporins.

• These agents are active against most G + and G▬ ve bacteria, including anaerobes, and are among the antibiotics of choice for infections caused by organisms producing AmpC or extended-spectrum B-lactamases (ESBLs).

Treatment for Carbapenems

• Important agents for treatment of many antibiotic-resistant bacterial infections at most body sites.

• Commonly used for severe polymicrobial infections, including Fournier's gangrene, severe intra-abdominal infections, & sepsis in immunocompromised hosts.

• Notable bacteria (resistant to carbapenems: ampicillin-resistant enterococci, MRSA, Stenotrophomonas, Burkholderia, Klebsiella pneumoniae, carbapenemase- (KPC-) producing gram-negative organisms.

• Ertapenem does not provide reliable coverage against P. aeruginosa, Acinetobacter, or enterococci;

• therefore, imipenem, doripenem, or meropenem would be preferred for empiric treatment of nosocomial infections when these pathogens are suspected.

• Meropenem is the preferred carbapenem for treatment of CNS infections.

• Carbapenems Can precipitate seizure activity, especially in older patients, individuals with renal insufficiency, and patients with preexisting seizure disorders or CNS pathology.

• Carbapenems should be avoided in these patients unless no reasonable alternative therapy is available. Like cephalosporins,

• Carbapenems have been rarely associated with anaphylaxis, interstitial nephritis, anemia, and leukopenia.

• Patients who are allergic to PCNs/cephalosporins may have a cross-hypersensitivity reaction to Carbapenems, and these agents should not be used in a patient with a reported severe PCN allergy without prior skin testing, desensitization, or both.

• Prolonged therapy (>2 weeks) is typically monitored with a weekly serum creatinine, LFTs, and CBC.


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Aminoglycosides (Amgs)

• Exert their bactericidal effect by binding to the bacterial ribosome, causing misreading during translation of bacterial messenger RNA into proteins.

• Often used in combination with cell wall–active agents (i.e., B-lactams and vancomycin) for treatment of severe infections caused by G + and G - aerobes.

• tend to be synergistic with cell wall–active antibiotics such as PCNs, cephalosporins, and vancomycin.

• Do not have activity against anaerobes, and their activity is impaired in the low pH/low O2 environment of abscesses.

• Cross-resistance among Amgs is common and in cases of serious infections, susceptibility testing with each Amg is recommended.

• Limitation (significant nephrotoxicity & ototoxicity).

• Traditional dosing of Amgs involves daily divided doses with the upper end of the dosing range reserved for life-threatening infections.

• Peak & trough concentrations should be obtained with the 3rd or 4th dose then every 3-4 days, along with regular serum creatinine monitoring.

• Increasing s. creatinine or peak/troughs out of the acceptable range require immediate attention.

• Extended-interval dosing of Amgs is an alternative method of administration and is more convenient than traditional dosing for most indications.

• A drug concentration is obtained 6-14 hrs after the 1st dose.

• Monitoring (obtaining a drug concentration 6-14 hrs after the dose at least every week and a s. creatinine at least 3x /week.

• In patients (not responding to Rx), a 12-hr concentration should be checked, if that concentration is undetectable, extended-interval dosing should be avoided and traditional dosing used instead.

• Nephrotoxicity is the major adverse effect of Amgs. which reversible when detected early but can be permanent, especially in patients with impaired renal function due to other medical conditions and should be used cautiously or avoidedin patients with decompensated kidney disease.

• Concomitant administration of Amgs +other known nephrotoxic (Amphotericin B formulations, foscarnet, nonsteroidal anti-inflammatory drugs pentamidine, polymyxins, cidofovir, and cisplatin) should be avoided if possible.

• Ototoxicity (vestibular or cochlear) adverse event that necessitates baseline & weekly hearing tests with extended therapy (>14 days).


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1) Gentamicin & Tobramycin

Extended-interval dosing is an initial 5 mg/kg, with the subsequent dosing interval determined by a nomogram

Tobramycin is also available as an inhaled agent for adjunctive therapy for cystic fibrosis or bronchiectasis complicated by P. aeruginosa infection (300 mg inhalation q12h).

2) Amikacin

Additional unique role for mycobacterial and Nocardia infections.

Extended-interval dosing is 15 mg/kg, with the subsequent dosing interval determined by a nomogram

Nephrotoxicity is the major adverse effect of aminoglycosides. Nephrotoxicity is reversible when detected early but can be permanent, especially in patients with impaired renal function due to other medical conditions. Aminoglycosides should be used cautiously or avoided, if possible, in patients with decompensated kidney disease.

Ototoxicity (vestibular or cochlear) is another possible adverse event that necessitates baseline and weekly hearing tests with extended therapy (>14 days). Concomitant administration of aminoglycosides with other known nephrotoxic agents (i.e., amphotericin B formulations, foscarnet, nonsteroidal anti-inflammatory drugs, pentamidine, polymyxins, cidofovir, and cisplatin) should be avoided if possible.

Vancomycin

• for meningitis

• A glycopeptide antibiotic that interferes with cell wall synthesis by binding to d-alanyl-d-alanine precursors that are critical for peptidoglycan cross-linking in most gram-positive bacterial cell walls.

• Bactericidal for staphylococci, but bacteriostatic for enterococci.

• Today, most hospitals are reporting increased incidence of colonization and infection with vancomycin-resistant Enterococcus faecium (VRE), and there are now reports of clinical isolates of S. aureus that are intermediately resistant (VISA) and resistant to vancomycin (VRSA)

• Patients with advanced renal disease should receive a single 15 mg/kg dose and then be re-dosed when the concentration drops below 10-20 mcg/mL.

• Vancomycin is typically administered by slow IV infusion over at least 1 hour. More rapid infusion rates can cause the red man syndrome, a histamine-mediated reaction that typically manifests by flushing and redness of the upper body.

• Nephrotoxicity, ototoxicity, neutropenia, thrombocytopenia, and rash may also occur.


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Fluoroquinolones

• Bactericidal effect by inhibiting bacterial DNA gyrase and topoisomerase, which are

critical for DNA replication.

• In general, well absorbed orally, serum concentrations that approach those of

parenteral administration.

• Typically have poor activity against enterococci, although fluoroquinolones with

substantial renal excretion may have some efficacy for enterococcal UTIs when other

agents are inactive or contraindicated.

Norfloxacin

• UTIs caused by G ┼ ▬ ve bacilli; however, other fluoroquinolones are preferred in this

setting.

• This agent should not be used to treat systemic infections.

Ciprofloxacin

Ofloxacin

• are active against G ▬ ┼ ve aerobes including many AmpC B -lactamase–producing

pathogens.

• Commonly used for UTIs, pyelonephritis, infectious diarrhea, prostatitis, intra-

abdominal infections (with metronidazole).

• Ciprofloxacin is the most active quinolone against P. aeruginosa

• Ciprofloxacin is the quinolone of choice for serious infections with that pathogen.

• However, ciprofloxacin has relatively poor activity against G ┼ ve cocci and anaerobes

• Should not be used as empiric monotherapy for community-acquired pneumonia, skin

and soft tissue infections, or intra-abdominal infections.

• Oral and IV ciprofloxacin give similar maximum serum levels; thus, oral therapy is

appropriate unless contraindicated.

Levofloxacin , Moxifloxacin , Gemifloxacin

All have improved coverage of streptococci, but less G▬ ve activity (especially against P.

aeruginosa) than ciprofloxacin.


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Moxifloxacin may be used as monotherapy of complicated intra-abdominal or skin and soft

tissue infections due to its anti-anaerobic activity.

• Each of these agents is useful for treatment of sinusitis, bronchitis, community-acquired

pneumonia, UTIs

• Except Moxifloxacin, which is only minimally eliminated in the urine.

• Some of these agents have activity against mycobacteria and have a potential role in

treating drug-resistant TB and atypical mycobacterial infections.

Levofloxacin may be used as an alternative for treatment of chlamydial urethritis.

Adverse reactions of flurocuinlones:

• Nausea, CNS disturbances (headache, restlessness, and dizziness, especially in the

elderly), rash, and phototoxicity.

• Can cause prolongation of the QTc interval, should not be used in patients who are

receiving class I or III antiarrhythmics, in patients with known electrolyte or conduction

abnormalities, or who are taking other medications that prolong the QTc interval or

induce bradycardia.

Should be used cautiously in elderly, in whom asymptomatic conduction disturbances are

more common.

• Fluoroquinolones should not be routinely used in patients younger than 18 years or in

pregnant or lactating women due to the risk of arthropathy in pediatric patients.

• May also cause tendinitis or tendon rupture, especially the Achilles tendon particularly

in elderly patients.

• Oral should not be given within 2 hrs of oral polyvalent metallic cation-containing agents

(e.g. iron, magnesium, calcium, zinc) or liquid nutritional supplements to avoid the

possibility of fluoroquinolone adsorption.

• This class has major DIs, necessitating that concomitant medication be checked for

safety of concurrent fluoroquinolone use.

Macrolide and Lincosamide Antibiotics

• Bacteriostatic agents that block ptn synthesis in bacteria by binding to the 50s subunit of

the bact. ribosome.


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• Has activity against G┼ cocci, including streptococci & staphylococci, & some upper

respiratory G▬ve bact, but minimal activity against enteric G▬ ve rods.

• Macrolides commonly used in pharyngitis, otitis media, sinusitis, bronchitis, especially in

PCN-allergic patients,

Among the drugs of choice for treating Legionella, Chlamydia, Mycoplasma infections.

• Azithromycin and clarithromycin can be used as monotherapy for outpatient

community-acquired pneumonia and have a unique role in the treatment and

prophylaxis of Mycobacterium avium complex (MAC) infections in patients with HIV.

• Many PCN-resistant strains of pneumococci are also resistant to macrolides.

Erythromycin

• Activity against G┼ve cocci (except enterococci), bronchitis, pharyngitis, sinusitis, otitis

media, soft tissue infections in PCN-allergic patients.

• Atypical RTIs due to Legionella pneumophila (1 g IV q6h), Chlamydophila pneumoniae,

Mycoplasma pneumoniae.

• Significant resistance to erythromycin among Haemophilus influenzae species and

therefore, efficacy of this drug for U & LRTIs is limited.

• Used for Chlamydia trachomatis infections (500 mg PO q6h for 7 days). as an alternate

therapy for syphilis in PCN-allergic. Use is limited by poor tolerability and drug

interactions.

Clarithromycin

• has a spectrum of activity similar to that of erythromycin but with enhanced activity

against some respiratory pathogens (especially Haemophilus).

• commonly used in bronchitis, sinusitis, otitis media, pharyngitis, soft tissue infections,

and community-acquired pneumonia.

has a prominent role in treating MAC infection in HIV patients and is an important

component of regimens used to eradicate Helicobacter pylori


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Azithromycin

has a similar spectrum of activity to clarithromycin and is commonly used to treat

bronchitis, sinusitis, otitis media, pharyngitis, soft tissue infections, and community-

acquired pneumonia.

• It has a prominent role in MAC prophylaxis (and treatment in HIV patients.

• It is also commonly used to treat C. trachomatis infections (1 g PO single dose).

A major advantage of azithromycin is that it does not have the numerous drug interactions

seen with erythromycin and clarithromycin.

Clindamycin

• Chemically classified as a lincosamide (related to macrolides), with a predominantly G┼

ve spectrum similar to that of erythromycin with additional activity against most

anaerobes, including B. fragilis.

• has excellent oral bioavailability (90%), penetrates well into bone and abscess cavities.

• used for aspiration pneumonia & lung abscesses.

• often active against community-acquired strains of MRSA, has emerged as a option for

skin, soft tissue infections caused by this organism.

• As a second agent in combination therapy for invasive streptococcal and clostridial

infections to decrease toxin production.

• suspected anaerobic infections (peritonsillar/retropharyngeal abscesses, necrotizing

fasciitis, although metronidazole is used more commonly for intra-abdominal infections

(clindamycin has less reliable activity against B. fragilis).

additional in babesiosis (in combination with quinine), toxoplasmosis (in combination with

pyrimethamine), Pneumocystis jiroveci pneumonia (in combination with primaquine).

Macrolides and clindamycin

• associated with nausea, abdominal cramping, and LFT abnormalities (particularly

erythromycin).

• Liver function profiles should be checked intermittently during extended therapy.


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• Hypersensitivity reactions with prominent skin rash are more common with clindamycin,

as is pseudomembranous colitis secondary to C lostridium difficile.

• Erythromycin and clarithromycin have major drug interactions caused by inhibition of

the cytochrome P-450 system.

Sulfonamides and Trimethoprim

• Sulfadiazine, sulfamethoxazole, trimethoprim

• inhibit folic acid metabolism.

• Most commonly used for uncomplicated UTIs.

Some sulfonamide-containing agents also have unique roles in the treatment of P. jiroveci,

Nocardia, Toxoplasma, and Stenotrophomonas infections

Trimethoprim

• Occasionally as monotherapy for UTIs.

• Often combination preparations outlined in the following

• Trimethoprim in combination with dapsone is an alternate therapy for mild P. jiroveci

pneumonia.

Trimethoprim/sulfamethoxazole

• Combination IV or PO with a 1:5 ratio of trimethoprim to sulfamethoxazole.

• IV preparation (based on the trimethoprim component) for serious infections.

• Oral preparations (160 mg trimethoprim/800 mg sulfamethoxazole per double-strength

[DS] tablet) are extensively bioavailable, with similar drug concentrations obtained with

IV and PO formulations.

• Both components have excellent tissue penetration, including bone, prostate, and CNS.

• The combination has a broad spectrum of activity but typically does not inhibit P.

aeruginosa, anaerobes, or group A streptococci.

• Therapy of choice for P. jiroveci pneumonia, Stenotrophomonas maltophilia,

Tropheryma whippelii, and Nocardia infections.


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• It is commonly used for treating sinusitis, otitis media, bronchitis, prostatitis, and UTIs (1

DS PO q12h).

• Trimethoprim/sulfamethoxazole is active against the majority of community-acquired

strains of MRSA, the agent has emerged as a viable for uncomplicated cases of skin, soft

tissue infections caused by this organism (2-3 DS tabs PO q12h).

• Used as P. jiroveci pneumonia prophylaxis (1 DS PO twice a week, 3X/ week, or single

strength or DS daily) in HIV-infected patients, solid organ transplant patients, BM

transplant, patients receiving fludarabine.

IV therapy is routinely converted to the PO equivalent for patients who require prolonged

therapy.

• For serious infections, such as Nocardia brain abscesses, it may be useful to monitor

trimethoprim/sulfamethoxazole with sulfamethoxazole peaks (100-150 mcg/mL) and

troughs occasionally during the course of therapy and adjust dosing accordingly.

• In patients with renal insufficiency, doses can be adjusted by following trimethoprim

peaks

• Prolonged therapy can cause BM suppression, possibly requiring treatment with

leucovorin (5-10 mg PO q24h) until cell counts normalize.

• Sulfadiazine (1.0-1.5 g PO q6h) in combination with pyrimethamine (200 mg PO

followed by 50 to 75 mg PO q24h) and leucovorin (10 to 20 mg PO q24h) is the therapy

of choice for toxoplasmosis.

• Sulfadiazine is also occasionally used to treat Nocardia infections.

• These drugs associated with cholestatic jaundice, BM suppression, hyperkalemia (with

Trimethoprim/sulfamethoxazole) interstitial nephritis, "false" elevations in s.

creatinine, severe hypersensitivity rexs (Stevens–Johnson syndrome/erythema

multiforme).

Nausea is common with higher doses. All patients should be asked whether they are

allergic to "sulfa drugs," and specific commercial names should be mentioned (i.e., Bactrim

or Septra)


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Tetracyclines

• Bacteriostatic bind to the 30S ribosomal subunit and block ptn synthesis.

• have unique roles in Rickettsia, Ehrlichia, Chlamydia, Mycoplasma infections.

• Most tick-borne infections, lyme disease–related arthritis, alternate therapy for syphilis,

P. multocida infections in PCN-allergic patients.

• use is limited because of widespread resistance among more common bacterial

pathogens.

• Both minocycline and doxycycline also have activity against some multidrug-resistant

G▬ve pathogens and may be used as adjunctive agents

Tetracycline

• Severe acne and in some H. pylori eradication regimens.

• Acute Lyme borreliosis, Rocky Mountain spotted fever, ehrlichiosis, psittacosis,

Mycoplasma pneumonia, Chlamydia pneumonia, chlamydial infections of the eye or

genitourinary tract, but these infections are generally treated with doxycycline or other

antibiotics.

Doxycycline

• Most commonly used tetracycline and is standard therapy for C. trachomatis, Rocky

Mountain spotted fever, ehrlichiosis, psittacosis.

• Has a role for malaria prophylaxis and for treatment of community-acquired

pneumonia.

Minocycline

is similar to doxycycline in its spectrum of activity and clinical indications.

2nd line therapy for pulmonary nocardiosis and cervicofacial actinomycosis and is

occasionally used for multidrug-resistant G▬ve infections.

• Nausea and photosensitivity are common side effects.

• Patients should be warned about sun exposure.

• Rarely, these medications are associated with pseudotumor cerebri.


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• They should not routinely be given to children or to pregnant or lactating women

because they can cause tooth enamel discoloration in young children.

• Minocycline is associated with vestibular disturbances. Aluminum- and magnesium-

containing antacids and preparations that contain oral calcium, oral iron, or other

cations can significantly impair the oral absorption of tetracyclines and should be

avoided within 2 hours of each dose.

Antimicrobial Agents, Miscellaneous

• Chloramphenicol

• Colistin and Polymyxin B

• Daptomycin

• Fosfomycin

• Linezolid

• Methenamine

• Metronidazole

• Nitrofurantoin

• Quinupristin/Dalfopristin

• Telavancin

• Tigecycline

pharmacology- antibiotics assist.prof.dr. hussam a-humadi · 2018-08-31 · pharmacology-...

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