THERAPEUTIC USES OF ANTIBIOTICS

Dr. S. A. ZIAI

Associate Professor

Department of Pharmacology

Shahid Beheshti University of Medical Sciences

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Pneumococcal Infections

Pneumococcal Pneumonia

Pneumococcal Meningitis

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Pneumococcal Infections:– Penicillin G is choice for infections caused by

sensitive strains of S. pneumoniae, but resistance is an increasing problem.

pneumococcal pneumonia – a third-generation cephalosporin or high-dose

penicillin G (i.e., 20–24 million units daily by continuous intravenous infusion)

– Therapy should be continued for 7-10 days, including 3-5 days after the patient's temperature has returned to normal.

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Pneumococcal MeningitisUntil it is established that the infecting pneumococcus is sensitive to penicillin, pneumococcal meningitis should be treated with a combination of vancomycin and a third-generation cephalosporin

Dexamethasone given at the same time as antibiotics was associated with an improved outcome

The recommended therapy is 20-24 million units of penicillin G daily by constant intravenous infusion or divided into boluses given every 2-3 hours. The usual duration of therapy is 14 days.

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Streptococcal Pharyngitis (Including Scarlet Fever)

Streptococcal Toxic Shock and Necrotizing Fascitis

Streptococcal Pneumonia, Arthritis, Meningitis, and Endocarditis

Infections Caused by Other Streptococci

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Streptococcal Infections:Pharyngitis is the most common disease produced by S. pyogenes (group A β-hemolytic streptococcus). – The preferred oral therapy is with penicillin V, 500 mg

every 6 hours for 10 days. – Penicillin therapy reduces the risk of subsequent

acute rheumatic fever (not glomerulonephritis).

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Streptococcal Toxic Shock :– These life-threatening infections are best treated with

penicillin plus clindamycin (to decrease toxin synthesis).

Streptococcal Pneumonia, Arthritis, Meningitis, and Endocarditis: – penicillin G; daily doses of 12–20 million units are

administered intravenously for 2–4 weeks (4 weeks for endocarditis).

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Infections Caused by Other StreptococciThe viridans group of streptococci are the most common cause of infectious endocarditis. These are nongroupable α-hemolytic microorganisms that are increasingly resistant to penicillin G (minimum inhibitory concentration [MIC] >0.1 µg/mL).

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Because enterococci also may be α-hemolytic, and certain other α-hemolytic strains may be relatively resistant to penicillin, it is important to determine quantitative microbial sensitivities to penicillin G in patients with endocarditis.

Patients with penicillin-sensitive VIRIDANS group streptococcal endocarditis can be treated successfully with daily doses of 12-20 million units of intravenous penicillin G for 2 weeks in combination with gentamicin 1 mg/kg every 8 hours. Some physicians prefer a 4-week course of treatment with penicillin G alone.

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Enterococcal endocarditis is one of the few diseases treated optimally with two antibiotics. The recommended therapy for penicillin- and aminoglycoside-sensitive enterococcal endocarditis is 20 million units of penicillin G or 12 g ampicillin daily administered intravenously in combination with a low dose of gentamicin.

Therapy usually should be continued for 6 weeks, but selected patients with a short duration of illness (<3 months) have been treated successfully in 4 weeks

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Infections with Anaerobes:Many anaerobic infections are polymicrobial, and most of the organisms are sensitive to penicillin G.

B. fragilis group, 75% of which may be resistant.

Brain abscesses contain several species of anaerobes, and most experts use high doses of penicillin G (20 million units per day) plus metronidazole Or Chloramphenicol.

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Pulmonary and periodontal infections (with the exception of β-lactamase-producing Prevotella melaninogenica) usually respond well to penicillin G, although a multicenter study indicated that clindamycin is more effective than penicillin for therapy of lung abscess

Mild-to-moderate infections at these sites may be treated with oral medication (either penicillin G or penicillin V 400,000 units [250 mg] four times daily)

More severe infections should be treated with 12–20 million units of penicillin G intravenously.

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Staphylococcal Infections: – Patients with staphylococcal infection should

receive penicillinase-resistant penicillins (e.g., nafcillin or oxacillin).

– HA-MRSA: Vancomycin, linezolid, quinupristin-dalfopristin, and daptomycin

– CA-MRSA: trimethoprim-sulfamethoxazole, doxycycline, and clindamycin

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Meningococcal Infections:Penicillin G is the drug of choice for meningococcal disease.

Patients should be treated with high doses of penicillin given intravenously.

Penicillin G does not eliminate the meningococcal carrier state and is ineffective for prophylaxis.

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Gonococcal InfectionsUncomplicated gonococcal urethritis is the most common infection, and a single intramuscular injection of 250 mg ceftriaxone is the recommended treatment.

Arthritis, disseminated gonococcal infections with skin lesions, and gonococcemia should be treated with ceftriaxone 1 g daily given either intramuscularly or intravenously for 7-10 days.

Ophthalmia neonatorum also should be treated with ceftriaxone for 7-10 days (25-50 mg/kg per day intramuscularly or intravenously).

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SyphilisPrimary, secondary, and latent syphilis of <1-year duration may be treated with penicillin G procaine (2.4 million units per day intramuscularly) plus probenecid (1.0 g/day orally) for 10 days or with 1-3 weekly intramuscular doses of 2.4 million units of penicillin G benzathine (three doses in patients with HIV infection).

Because neurosyphilis, & cardiovascular syphilis are potentially lethal and their progression can be halted (but not reversed), intensive therapy with 20 million units of penicillin G daily for 10 days is recommended.

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There are no proven alternatives for treating syphilis in pregnant women, so penicillin-allergic individuals must be acutely desensitized to prevent anaphylaxis

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Infants with congenital syphilis discovered at birth or during the postnatal period should be treated for at least 10 days with 50,000 units/kg daily of aqueous penicillin G in two divided doses or 50,000 units/kg of procaine penicillin G in a single daily dose

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Most patients (70-90%) with secondary syphilis develop the Jarisch-Herxheimer reaction. Several hours after the first injection of penicillin, chills, fever, headache, myalgias, and arthralgias may develop. Manifestations usually persist for a few hours, and the rash begins to fade within 48 hours. Aspirin gives symptomatic relief, and therapy with penicillin should not be discontinued.

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ActinomycosisPenicillin G is the agent of choice for the treatment of all forms of actinomycosis.

The dose should be 10-20 million units of penicillin G intravenously per day for 6 weeks. Some physicians continue therapy for 2-3 months with oral penicillin V (500 mg four times daily).

Surgical drainage or excision of the lesion may be necessary before cure is accomplished.

Natural PenicillinsDiphtheriaThere is no evidence that penicillin or any other antibiotic alters the incidence of complications or the outcome of diphtheria; specific antitoxin is the only effective treatment. However, penicillin G eliminates the carrier state.

The parenteral administration of 2-3 million units per day in divided doses for 10-12 days eliminates the diphtheria bacilli from the pharynx and other sites in practically 100% of patients.

A single daily injection of penicillin G procaine for the same period produces comparable results.

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Anthrax

Strains of Bacillus anthracis resistant to penicillin have been recovered from human infections.

When penicillin G is used, the dose should be 12-20 million units per day.

Natural PenicillinsClostridial InfectionsPenicillin G is the agent of choice for gas gangrene; the dose is in the range of 12-20 million units per day given parenterally as an adjunct to the antitoxin.

Adequate debridement of the infected areas is essential.

Natural PenicillinsAntimicrobial drugs probably have no effect on the ultimate outcome of tetanus.

Debridement and administration of human tetanus immune globulin may be indicated.

Penicillin is administered, however, to eradicate the vegetative forms of the bacteria that may persist.

Metronidazole is preferred

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Fusospirochetal Infections

Gingivostomatitis, produced by the synergistic action of Leptotrichia buccalis and spirochetes that are present in the mouth, is readily treatable with penicillin. For simple "trench mouth," 500 mg penicillin V given every 6 hours for several days is usually sufficient to clear the disease.

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Rat-Bite Fever

The two microorganisms responsible for this infection, Spirillum minor in the Far East and Streptobacillus moniliformis in America and Europe, are sensitive to penicillin G, the therapeutic agent of choice.

Because most cases due to Streptobacillus are complicated by bacteremia and, in many instances, by metastatic infections, especially of the synovia and endocardium, the dose should be large; a daily dose of 12-15 million units given parenterally for 3-4 weeks has been recommended.

Natural PenicillinsListeria Infections

Ampicillin (with gentamicin for immunosuppressed patients with meningitis) and penicillin G are the drugs of choice in the management of infections owing to L. monocytogenes.

The recommended dose of ampicillin is 1-2 g intravenously every 4 hours. The recommended dose of penicillin G is 15-20 million units parenterally per day for at least 2 weeks.

When endocarditis is the problem, the dose is the same, but the duration of treatment should be no less than 4 weeks.

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Lyme Disease

Although a tetracycline is the usual drug of choice for early disease, amoxicillin is effective; the dose is 500 mg three times daily for 21 days.

Severe disease is treated with a third-generation cephalosporin or up to 20 million units of intravenous penicillin G daily for 10-14 days.

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Erysipeloid

The causative agent of this disease, Erysipelothrix rhusiopathiae, is sensitive to penicillin.

The uncomplicated infection responds well to a single injection of 1.2 million units of penicillin G benzathine.

When endocarditis is present, penicillin G, 12-20 million units per day, has been found to be effective; therapy should be continued for 4-6 weeks.

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Pasteurella Multocida

Pasteurella multocida is the cause of wound infections after a cat or dog bite.

It is uniformly susceptible to penicillin G and ampicillin and resistant to penicillinase-resistant penicillins and first-generation cephalosporins.

When the infection causes meningitis, a third-generation cephalosporin is preferred because the MICs are slightly lower than for penicillin.

PROPHYLACTIC USES OF THE PENICILLINS

Streptococcal Infections:– The administration of penicillin to individuals exposed

to S. pyogenes protects against infection.– The oral ingestion of 200,000 units of penicillin G or

penicillin V twice a day or a single injection of 1.2 million units of penicillin G benzathine is effective.

– Indications for this type of prophylaxis include outbreaks of streptococcal disease in closed populations, such as boarding schools or military bases. Patients with extensive deep burns are at high risk of severe wound infections with S. pyogenes; "low-dose" prophylaxis for several days appears to be effective

PROPHYLACTIC USES OF THE PENICILLINS

Syphilis:– Prophylaxis for a contact with syphilis consists of a

course of therapy as described for primary syphilis.

PROPHYLACTIC USES OF THE PENICILLINS

Recurrences of Rheumatic Fever– The intramuscular injection of 1.2 million units of

penicillin G benzathine once a month yields excellent results.

– In cases of hypersensitivity to penicillin, sulfisoxazole or sulfadiazine, 1 g twice a day for adults, also is effective; for children weighing <27 kg, the dose is halved.

Surgical Procedures in Patients with Valvular Heart Disease– About 25% of cases of subacute bacterial endocarditis

follow dental extractions.

Penicillinase-Resistant Penicillins

ISOXAZOLYL

OXACILLIN

CLOXACILLIN

DICLOXACILLIN semisynthetic penicillins are similar structurally and pharmacologically.

All are relatively stable in an acid medium and are absorbed adequately after oral administration.

All are markedly resistant to cleavage by penicillinase

Penicillinase-Resistant Penicillins

Penicillinase-Resistant Penicillins

AMINOPENICILLINS

Enterococci are about twice as sensitive to ampicillin as they are to penicillin G.

From 30-50% of E. coli, a significant number of P. mirabilis, and practically all species of Enterobacter presently are insensitive.

These antibiotics are less active against B. fragilis than penicillin G

AMINOPENICILLINS

AMINOPENICILLINS

AMINOPENICILLINS

Upper Respiratory Infections– Active against S. pyogenes and many strains

of S. pneumoniae and H. influenza– Sinusitis, otitis media, acute exacerbations of

chronic bronchitis, and epiglottitis

AMINOPENICILLINS

– 20-30% of strains of S. pneumoniae now may be resistant to ampicillin

– Amoxicillin is the most active of all the oral β-lactam antibiotics against both penicillin-sensitive and penicillin-resistant S. pneumoniae.

– Based on the increasing prevalence of pneumococcal resistance to penicillin, an increase in dose of oral amoxicillin (from 40-45 up to 80-90 mg/kg per day) for empirical treatment of acute otitis media in children is recommended

AMINOPENICILLINS

Urinary Tract Infections – Most uncomplicated urinary tract infections are

caused by Enterobacteriaceae, and E. coli is the most common species; ampicillin often is an effective agent.

– Enterococcal urinary tract infections are treated effectively with ampicillin alone.

AMINOPENICILLINS

Meningitis– Ampicillin has excellent activity against L.

monocytogenes, which causes meningitis in immunocompromised persons.

– combination of ampicillin and vancomycin plus a third-generation cephalosporin is a rational regimen for empirical treatment of suspected bacterial meningitis.

AMINOPENICILLINS

Salmonella Infections – A fluoroquinolone or ceftriaxone is considered by

some to be the drug of choice, but the administration of trimethoprim-sulfamethoxazole or high doses of ampicillin (12 g/day for adults) also is effective.

– In some geographic areas, resistance to ampicillin is common.

– The typhoid carrier state has been eliminated successfully in patients without gallbladder disease with ampicillin, trimethoprim-sulfamethoxazole, or ciprofloxacin.

CARBOXYPENICILLINS

Carbenicillin and ticarcillin are active against some isolates of P. aeruginosa and certain indole-positive Proteus spp.

They are ineffective against most strains of S. aureus, Enterococcus faecalis, Klebsiella, and L. monocytogenes.

B. fragilis is susceptible to high concentrations of these drugs, but penicillin G is actually more active.

UREIDOPENICILLINS

Mezlocillin and piperacillin, have superior activity against P. aeruginosa compared with carbenicillin and ticarcillin.

Mezlocillin and piperacillin are useful for treatment of infections with Klebsiella.

Piperacillin and related agents are important agents for the treatment of patients with serious infections caused by gram-negative bacteria.

UREIDOPENICILLINS

Nosocomial infections in immune-compromised patients.

These penicillins find their greatest use in treating bacteremias, pneumonias, infections following burns, and urinary tract infections owing to microorganisms resistant to penicillin G and ampicillin

The bacteria especially responsible include P. aeruginosa, indole-positive strains of Proteus, and Enterobacter spp.

UREIDOPENICILLINS

Cephalosporins

First-generation

Are excellent agents for skin and soft tissue infections owing to S. aureus and S. pyogenes.

A single dose of cefazolin just before surgery is the preferred prophylaxis for procedures in which skin flora are the likely pathogens.

Gram-positive bacteria

Streptococcus pyogenes, Some virdans streptococci, Some Staphylococcus aureus, Some Streptococcus pneumoniae

Gram-negative bacteria

Some Eschericia coli, Some Klebsiella pneumoniae, Some Proteus mirabilis

Gram-positive bacteria True cephalosporins have activity equivalent to first-generation agents. Cefoxitin and cefotetan have little activity

Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae, Neisseria spp.

Anaerobic bacteria Cefoxitin and cefotetan have moderate anaerobic activity.

Second-generation

Cefoxitin: special role is for treatment of certain anaerobic and mixed aerobic-anaerobic infections,

such as pelvic inflammatory disease and lung abscess.

Cefaclor is more active against H. influenzae and Moraxella catarrhalis than cephalexine.

Second-generation

Cefuroxime: Against some Citrobacter and Enterobacter spp.

Concentrations in CSF are ~10% of those in plasma; the drug is effective for treatment of meningitis owing to H. influenzae (including strains resistant to ampicillin), N. meningitidis, and S. pneumoniae.

Second-generation

Cefotetan: Hypoprothrombinemia and inhibition of vitamin K activation with bleeding have occurred in malnourished.

For colorectal surgery, where prophylaxis for intestinal anaerobes is desired, the second-generation agents, cefoxitin or cefotetan, are preferred.

Second-generation

Third-generation cephalosporins are the drugs of choice for serious infections caused by Klebsiella, Enterobacter, Proteus, Providencia, and Haemophilus spp.

They are the drugs of choice for meningitis caused by H. influenzae, sensitive S. pneumoniae, N. meningitidis, and gram-negative enteric bacteria.

Third-generation

Third-generation

Cefotaxime is highly resistant to many β-lactamases and has good activity against many bacteria.

Cefotaxime has been used effectively for meningitis caused by H. influenzae, penicillin-sensitive S. pneumoniae, and N. meningitides.

Ceftriaxone is the drug of choice for all forms of gonorrhea and for severe forms of Lyme disease.

A single dose of ceftriaxone (125–250 mg) is effective in the treatment of urethral, cervical, rectal, or pharyngeal gonorrhea, including penicillinase- producing microorganisms.

Third-generation

Gram-positive bacteria Streptococcus pyogenes, Viridans streptococci, Many Streptocossus pneumoniae. Modest activity against Staphylococcus aureus

Gram-negative bacteria Escherichia coli, Klebsiella pneumoniae, Proteus spp. Haemophilus influenzae, Neisseria spp. Many other Enterobacteriaceae, Pseudomonas aeruginosa.

Fourth-generation

The fourth-generation cephalosporins are indicated for the empirical treatment of nosocomial infections.

For example, cefepime is superior to ceftazidime and piperacillin for nosocomial isolates of Enterobacter, Citrobacter, and Serratia spp.

Fourth-generation

Sulfonamides

Antibacterial spectrum

Resistance to sulfonamides is increasingly a problem. Microorganisms that may be susceptible in vitro to

sulfonamides include Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus ducreyi, Nocardia, Actinomyces, Calymmatobacterium granulomatis, and Chlamydia trachomatis.

Minimal inhibitory concentrations (MICs) range from 0.1 µg/mL for C. trachomatis to 4-64 µg/mL for Escherichia coli.

Peak plasma drug concentrations achievable in vivo are ~100-200 µg/mL.

Sulfonamide Therapy

Urinary Tract Infections

Nocardiosis

Toxoplasmosis

URINARY TRACT INFECTIONS : No longer a therapy of first choice :

because sulfonamide-resistant Trimethoprim–sulfamethoxazole

Patients with acute pyelonephritis with high fever are at risk of bacteremia and shock : Sulfonamide is contraindicated

Sulfonamide Therapy

Nocardiosis: Sulfisoxazole or sulfadiazine 6-8 g daily several months after all

manifestations have been controlled Therapy in advanced cases:

Sulfonamide +ampicillin/ erythromycin / streptomycin

Trimethoprim–sulfamethoxazole(choice)

Sulfonamide Therapy

TOXOPLASMOSIS :Treatment of choice:

Pyrimethamine + sulfadiazine + folinic acid + 2 L of fluid intake daily to prevent crystalluria

Sulfonamide Therapy

Use of Sulfonamides for Prophylaxis

Preventing streptococcal infections and recurrence of rheumatic fevers

Untoward responses usually occur during the first 8 weeks of therapy.

White blood cell counts should be carried out once weekly during the first 8 weeks.

TRIMETHOPRIM

The antibacterial spectrum of trimethoprim is similar to that of sulfamethoxazole, although trimethoprim is 20-100 times more potent.

Most gram-negative and gram-positive microorganisms are sensitive to trimethoprim, but resistance can develop when the drug is used alone.

Pseudomonas aeruginosa, Bacteroides fragilis, and enterococci usually are resistant.

There is significant variation in the susceptibility of Enterobacteriaceae to trimethoprim in different geographic locations because of the spread of resistance mediated by plasmids and transposons

Efficacy of Trimethoprim-Sulfamethoxazole in Combination

Chlamydia trachomatis and N. meningitidis are susceptible.

Although most S. pneumoniae are susceptible, there has been a disturbing increase in resistance.

From 50-95% of strains of Staphylococcus aureus, Staphylococcus epidermidis, S. pyogenes, the viridans group of streptococci, E. coli, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Enterobacter spp., Salmonella, Shigella, Pseudomonas pseudomallei, Serratia, and Alcaligenes spp. are inhibited.

Also sensitive are Klebsiella spp., Brucella abortus, Pasteurella haemolytica, Yersinia pseudotuberculosis, Yersinia enterocolitica, and Nocardia asteroides.

BACTRIM THERAPEUTIC USES

Urinary Tract Infections (UTI) & bacterial prostatitis

Bacterial Respiratory Tract Infections

Acute otitis media in children

GI Infections : shigellosis /Acute diarrhea

Infection by Pneumocystis jiroveci in patients with AIDS.

Prophylaxis in Neutropenic Patients

Nocardia infections

Urinary Tract Infections

Uncomplicated lower urinary tract infection (UTI) Single-dose therapy (320 mg trimethoprim plus 1600

mg sulfamethoxazole in adults)

A minimum of 3 days of therapy is more likely to be effective

In chronic and recurrent infections of the urinary tract

Small doses : reduce the number of recurrent urinary tract infections in women presence of therapeutic concentrations of trimethoprim

in vaginal secretions

Bacterial prostatitis

Bacterial Respiratory Tract Infections

Acute exacerbations of chronic bronchitis

Should not be used to treat streptococcal pharyngitis because it does not eradicate the microorganism

Acute otitis media in children & acute maxillary sinusitis in adults caused by susceptible strains of H. influenzae and S. pneumoniae

GI Infections

Shigellosis: Alternative to a fluoroquinolone

Typhoid fever: A second-line drug (ceftriaxone or a fluoroquinolone is the preferred treatment)

Travelers' diarrhea: for 5 days

Effective in the management of carriers of sensitive strains of Salmonella typhi and other Salmonella spp., however, failures have occurred.

Acute diarrhea owing to sensitive strains of enteropathogenic E. coli

However, antibiotic treatment of diarrheal illness owing to enterohemorrhagic E. coli O157:H7 may increase the risk of hemolytic-uremic syndrome, perhaps by increasing the release of Shiga toxin by the bacteria.

Infection by Pneumocystis jiroveci

High-dose therapy: effective for this severe infection in patients with AIDS

Adjunctive corticosteroids should be given at the onset of anti-Pneumocystis therapy

Adverse reactions are less frequent with the lower prophylactic doses

The most common problems are rash, fever, leukopenia, and hepatitis.sm in patients with AIDS

Prophylaxis in Neutropenic Patients

low-dose prophylaxis of infection by P. jiroveci

Significant protection against sepsis caused by g- in severely neutropenic patients

Miscellaneous Infections

Nocardia infections: treated successfully

Brucellosis treatment of choice: doxycycline +streptomycin or

gentamicin

trimethoprim-sulfamethoxazole may be an effective substitute for the doxycycline combination

Whipple's disease

Infection by Stenotrophomonas maltophilia

Intestinal parasites Cyclospora and Isospora

Wegener's granulomatosis depending on the stage of the disease

FLUOROQUINOLONES

ANTIBACTERIAL SPECTRUM

The fluoroquinolones are potent bactericidal agents against E. coli and various species of Salmonella, Shigella, Enterobacter, Campylobacter, and Neisseria (MIC90 usually are <0.2 μg/mL).

Fluoroquinolones also have good activity against staphylococci, but not against methicillin-resistant strains (MIC90 = 0.1-2 μg/mL).

Activity against streptococci is limited to a subset of the quinolones, including levofloxacin (LEVAQUIN), and moxifloxacin (AVELOX).

ANTIBACTERIAL SPECTRUM

Several intracellular bacteria are inhibited by fluoroquinolones at concentrations that can be achieved in plasma; these include species of Chlamydia, Mycoplasma, Legionella, Brucella, and Mycobacterium (including Mycobacterium tuberculosis).

Several fluoroquinolones, including gemifloxacin, have activity against anaerobic bacteria

URINARY TRACT INFECTIONS

The fluoroquinolones are more efficacious than trimethoprim–sulfamethoxazole

Norfloxacin and ciprofloxacin XR are approved for use in the U.S. only for UTIs.

PROSTATITIS

Norfloxacin, ciprofloxacin, and ofloxacin are effective for the treatment of prostatitis caused by sensitive bacteria Fluoroquinolones administered for 4–6 weeks appear to be effective in patients not responding to trimethoprim–sulfamethoxazole.

SEXUALLY TRANSMITTED DISEASES

The quinolones are contraindicated in pregnancy. Fluoroquinolones lack activity for Treponema pallidum Fluoroquinolones have activity in vitro against N.gonorrhoeae, Chlamydia trachomatis, and

Haemophilus ducreyi For chlamydial urethritis/cervicitis, a 7-day course of ofloxacin is an alternative to a 7-day course with doxycycline or a single dose of azithromycin. Chancroid (infection by H. ducreyi) can be treated with 3 days of ciprofloxacin.

SEXUALLY TRANSMITTED DISEASES

A single oral dose of a fluoroquinolone is effective treatment for sensitive strains of N. gonorrhoeae

Increasing resistance to fluoroquinolones has made ceftriaxone the first-line agent

Pelvic inflammatory disease has been treated effectively with a 14-day course of ofloxacin combined with an antibiotic with activity against anaerobes (clindamycin or metronidazole).

GASTROINTESTINAL AND ABDOMINAL INFECTIONS

For traveler’s diarrhea ,the quinolones are equal to trimethoprim–sulfamethoxazole in effectiveness, reducing the duration of loose stools by 1-3 days.

Norfloxacin, ciprofloxacin, and ofloxacin given for 5 days all are effective in the treatment of shigellosis Shigellosis is treated effectively with either

ciprofloxacin or azithromycin Norfloxacin is superior to tetracyclines in decreasing the duration of diarrhea in cholera.

GASTROINTESTINAL AND ABDOMINAL INFECTIONS

Ciprofloxacin and ofloxacin treatment cures most patients with enteric fever caused by S. typhi, as well as bacteremic nontyphoidal infections in AIDS patients, and clears chronic fecal carriage. The in vitro ability of the quinolones to induce the Shiga toxin (the cause of the hemolytic-uremic syndrome) in E. coli suggests that the quinolones should not be used for Shiga toxin–producing E. coli

RESPIRATORY TRACT INFECTIONS

The major limitation to the use of quinolones for the treatment of community-acquired pneumonia and bronchitis was the poor activity against S. pneumoniae and anaerobic bacteria

Newer fluoroquinolones, including gemifloxacin, levofloxacin and moxifloxacin, have excellent activity against S. pneumonia.

RESPIRATORY TRACT INFECTIONS

The fluoroquinolones have activity against H.influenzae, Moraxella catarrhalis, S. aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila.

Either a fluoroquinolone (ciprofloxacin or levofloxacin) or azithromycin is the antibiotic of choice for L. pneumophila.

Fluoroquinolones can effectively eradicate both

H. influenzae and M. catarrhalis from sputum.

Mild-to-moderate respiratory exacerbations owing

to P. aeruginosa in patients with cystic fibrosis have responded to oral fluoroquinolones

BONE, JOINT, AND SOFT TISSUE INFECTIONS

The treatment of chronic osteomyelitis requires prolonged antimicrobial therapy with agents active against S. aureus and gram-negative rods

Clinical cures have been as high as 75% in chronic osteomyelitis in which gram-negative rods predominated

BONE, JOINT, AND SOFT TISSUE INFECTIONS

Failures have been associated with the development of resistance in S. aureus, P. aeruginosa, and Serratia marcescens

Diabetic foot infections: the fluoroquinolones in combination with an agent with antianaerobic activity

OTHER INFECTIONS Levofloxacin is approved to treat and prevent

anthrax as well as plague due to Yersinia pestis

Treatment of tularemia

As part of treatment of multidrug-resistant tuberculosis and atypical mycobacterial infections as well as Mycobacterium avium complex infections in AIDS

Quinolones, when used as prophylaxis in neutropenic patients, have decreased the incidence of gram-negative rod bacteremias.

Macrolides

Respiratory Tract Infections Azithromycin and clarithromycin are suitable

choices for treatment of mild to moderate CAP among ambulatory patients.

In hospitalized patients, a macrolide is commonly added to a cephalosporin for coverage of atypical respiratory pathogens.

Azithromycin (or a fluoroquinolone) has supplanted erythromycin as the first-line agent for treatment of legionellosis.

The recommended dose is 500 mg daily, intravenously or orally, for a total of 10-14 days.

Macrolides are also appropriate alternative agents for the treatment of acute exacerbations of chronic bronchitis, acute otitis media, acute streptococcal pharyngitis, and acute bacterial sinusitis.

Skin and Soft-Tissue Infections

Macrolides are alternatives for treatment of erysipelas and cellulitis among patients who have a serious allergy to penicillin.

Chlamydial Infections

A single 1-g dose of azithromycin is recommended for patients with uncomplicated urethral, endocervical, rectal, or epididymal infections

During pregnancy, erythromycin base, 500 mg 4 times daily for 7 days, (or Azithromycin, 1 g orally as a single dose ) is recommended as first-line therapy for chlamydial urogenital infections.

Erythromycin base is preferred for chlamydial pneumonia of infancy and ophthalmia neonatorum (50 mg/kg/day in 4 divided doses for 10-14 days).

Azithromycin, 1 g/week for 3 weeks, may be effective for lymphogranuloma venereum.

THERAPEUTIC USES:

Diphtheria

Erythromycin 250 mg four times daily for 7 days is very effective for acute infections

Other macrolides likely are also effective but are not FDA-approved forthis indication

Antibiotics do not alter the course of an acute infection with diphtheria or decrease the risk of complications.

Pertussis

Erythromycin is the drug of choice for treating persons with B. pertussis disease

Clarithromycin and azithromycin also are effective

THERAPEUTIC USES:

Campylobacter Infections

Fluroquinolones largely have replaced erythromycin for this disease in adults.

Erythromycin remains useful for treatment of Campylobacter gastroenteritis in children.

THERAPEUTIC USES:

Helicobacter pylori Infection

Clarithromycin 500 mg, in combination with omeprazole, 20 mg, and amoxicillin, 1 g, each administered twice daily for 10–14 days, is effective for treatment of peptic ulcer disease caused by H. pylori.

Prophylactic Uses

Clarithromycin or azithromycin (or clindamycin) are recommended alternatives for the prevention of bacterial endocarditis in patients undergoing dental procedures.

Erythromycin is an effective alternative for the prophylaxis of recurrences of rheumatic fever in individuals who are allergic to penicillin.

Clindamycin Therapeutic uses

Clindamycin is the drug of choice for treatment of lung abscess and anaerobic lung and pleural space infections.

Clindamycin is not predictably useful for the treatment of bacterial brain abscesses; metronidazole, in combination with penicillin or a third-generation cephalosporin, is preferred.

Clindamycin is an alternative agent for the treatment of skin and soft-tissue infections, especially in patients with β-lactam allergies.

Clindamycin also is available as a topical solution, gel, or lotion and as a vaginal cream. It is effective topically (or orally) for acne vulgaris and bacterial vaginosis.

Clindamycin in combination with pyrimethamine and leucovorin (folinic acid, 10 mg/day) is effective for acute treatment of encephalitis caused by T. gondii in patients with AIDS.

TETRACYCLINES AND GLYCYLCYCLINES

Therapeutic Uses and Dosage• The tetracyclines have been used extensively to treat

infectious diseases such as rickettsiae, mycoplasmas, and chlamydiae and as an additive to animal feeds to facilitate growth

•The total daily dose of intravenous tetracycline for most acute infections is 1 g (or 2 g for

severe infection), administered at 6- or 12-hour intervals

•Children >8 years : 25-50 mg/kg daily in four divided doses .

Tetracycline

•The oral or intravenous dose for adults is 100 mg every 12 hours on the first day and then 50 mg

every 12 hours, 100 mg once a day, or 100 mg twice daily when severe infection is present

•for children >8 years of age, the dose is 4-5 mg/kg per day in two divided doses the first day, then 2-

2.5 mg/kg given once or twice daily

Doxycycline

…

•The dose for adults: 200 mg orally or intravenously initially, followed

by 100 mg every 12 hours•for children: 4 mg/kg initially

followed by 2 mg/kg every 12 hours

Minocycline

•Is administered intravenously to adults as a 100-mg loading dose,

followed by 50 mg every 12 hours•For children: wasn’t determined

Tigecycline

Some notes

• The low pH of tetracycline invariably causes phlebitis if infused into a peripheral vein

• Demeclocycline is used rarely as an antimicrobial agent : higher risks of photosensitivity reactions and nephrogenic diabetes insipidus

• Tetracyclines should not be administered intramuscularly because of local irritation and poor absorption. GI distress, nausea, and vomiting can be minimized by administration of tetracyclines with food

ANTIMICROBIAL ACTIVITY

• Tetracyclines are bacteriostatic antibiotics with activity against a wide range of aerobic and anaerobic gram-positive and gram-negative bacteria.

• Glycylcyclines have activity against bacteria that resistant to the first- and second-generation tetracyclines.

Therapeutic Uses

Respiratory Tract Infections •Doxycycline: good activity against S. pneumoniae and H. influenzae and excellent activity against atypical pathogens such as Mycoplasma and Chlamydophilia pneumoniae •Tigecycline : as a single agent for adults hospitalized with community-acquired bacterial pneumonia

Skin and Soft-Tissue Infections•Tetracycline, doxycycline, or minocycline: methicillin-resistant S. aureus often; complicated skin and soft-tissue infections•Tigecycline : complicated skin and soft-tissue infections•Tetracyclines: used for acne by inhibiting propionibacteria (250 mg bid)

Intra-Abdominal Infections •Tigecycline: excellent activity against these pathogens as well as Enterococcus •Tetracyclines: has limited utility (resistance among enterobacteriaceae and gram negative anaerobes)

…

GI Infections

•Tetracyclines: ineffective in infections caused by Shigella, Salmonella, or other

Enterobacteriaceae .•Doxycycline : 300 mg as a single dose is

effective in reducing stool volume and eradicating Vibrio cholerae from the stool

within 48 hours.

Urinary Tract Infections

•Tetracyclines: isn't recommended because of resistant microorganism

•Tigecycline: little experience

…

Sexually Transmitted

Diseases

•Doxycycline: no longer is recommended for gonococcal infections

•Doxycycline:Chlamydia trachomatis often is a coexistent pathogen in acute pelvic inflammatory

disease. 100 mg intravenously twice daily, is recommended for at least 48 hours followed by oral

therapy at the same dosage to complete a 14-day course .

•Doxycycline : Acute epididymitis is caused by infection with C. trachomatis or Neisseria

gonorrhoeae in men <35 years of age. Effective regimens include a single injection of ceftriaxone

(250 mg) plus doxycycline, 100 mg orally twice daily for 10 days.

•Doxycycline: for nonspecific urethritis 100 mg every 12 hours for 7 days; however, azithromycin is usually preferred because it can be given as a

single 1-g dose•Doxycycline: for lymphogranuloma venereum ,100

mg twice daily for 21 days•Non-pregnant penicillin-allergic patients who have

primary, secondary, or latent syphilis can be treated with a tetracycline regimen such as doxycycline,

100 mg orally twice daily for 2 weeks.•Tetracyclines should not be used for treatment of

neurosyphilis.

…

Local Application

•Except for local use in the eye, topical use of the tetracyclines is not

recommended .•Minocycline sustained-release

microspheres for subgingival administration are used in dentistry.

Other Infections

•Brucella spp: Tetracyclines in combination with rifampin or

streptomycin or doxycycline, 200 mg per day, plus rifampin, or the usual dose of

doxycycline plus streptomycin 1 g daily, intramuscularly

•Tularemia, Actinomycosis, Yaws and relapsing fever , leptospirosis , Borrelia spp, atypical mycobacterial pathogens

(M. marinum) : Tetracyclines •Nocardiosis: Minocycline

Therapeutic Uses and Dosage of Chloramphenicol

Typhoid Fever•Third-generation cephalosporins and quinolones are drugs of choice

for the treatment of typhoid fever because they are less toxic and because strains of Salmonella typhi often are resistant to

chloramphenicol

Bacterial Meningitis•Chloramphenicol remains an alternative drug for the treatment of

meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae in patients who have severe allergy to β-lactams and in

developing countries

AMINOGLYCOSIDES

Therapeutic Uses AGs often are combined with a penicillin or cephalosporin for the therapy of serious gram neg. infections: P. aeruginosa, Enterobacter, Klebsiella, Serratia, and other species resistant to less toxic antibiotics, including: UTI, bacteremia, infected burns, osteomyelitis, pneumonia, peritonitis, and otitis

STREPTOMYCIN Less active against aerobic gram-negative rods PenicillinG + Streptomycin for treatment of streptococcal or enterococcal endocarditis

Drug of choice for the treatment of tularemia Effective for all forms of plague Tuberculosis: Second line agent

GENTAMICIN Enterococcal endocarditis: concomitant administration of penicillin and gentamicin for 4-6 weeks has been recommended because of an unacceptably high relapse rate with penicillin alone

Gentamicin is generally preferred for its lesser toxicity; also, gentamicin should be used when the strain of enterococcus is resistant to streptomycin

AGs should never be mixed in the same solution with penicillins because inactivated by penicillin

Pneumonia AGs never used as the sole agent to treat pneumonia acquired in the community or initial treatment for pneumonia acquired in the hospital

UTI AGs usually are not indicated for the treatment of uncomplicated UTI, although a single IM dose of gentamicin (5 mg/kg) can cure more than 90% of uncomplicated infections of the lower urinary tract

Meningitis Third-generation cephalosporins has reduced the need for AG in most cases, except for gram neg. resistant to β-lactams (Pseudomonas & Acinetobacter)

Endocarditis Penicillin and gentamicin in combination are effective as a short-course (i.e., 2-week) regimen for uncomplicated native-valve streptococcal endocarditis

TOBRAMYCIN

Antimicrobial activity, PK properties, and

toxicity profile are very similar to

gentamicin

Preferred AG for treatment of serious

infections caused by P. aeruginosa

AMIKACINBroadest spectrum of antimicrobial activityResistant to many AG-inactivating enzymesIn hospitals where gentamicin-and tobramycin-resistant organisms are prevalentLess active than gentamicin against enterococciNot active against the majority of g+ anaerobicsFor M.tuberculosis, including streptomycin-resistant and atypical strains

NEOMYCINBroad-spectrum antibiotic

Gram-negative species that are highly sensitive are E.coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Proteus vulgaris

Gram-positive that are inhibited include S. aureus and E. faecalis

M.tuberculosis also is sensitive

Strains of P. aeruginosa are resistant

Irrigation of the bladder

Neomycin has been used topically in a variety of infections of the skin and

mucous membranes

VANCOMYCIN

A complex tricyclic glycopeptide

It acts by inhibiting cell wall synthesis

ACTIVITY

Gram-positive bacteria: S.aureus and S.epidermidis, also strains resistant to methicillin

S.pyogenes, S.pneumoniae, and viridans streptococci

B.anthracis is highly sensitive

Essentially all species of gram-negative bacilli and mycobacteria are resistant Is the result of alteration of the D-Ala-D-Ala target to D-Ala-D-lactate or D-Ala-D-Ser, which bind vancomycin poorly

THERAPEUTIC USES

Vanco-resistant enterococciMajor nosocomial pathogens in the U.S

Enterococcal resistance Pseudomembranous colitisVancomycin can be administered orally , although metronidazole is preferred

THERAPEUTIC USES

Should be used only to treat serious infections

like methicillin-resistant staphylococci and

severe staphylococcal infections in patients

allergic to penicillins and cephalosporins

Vancomycin is less rapidly bactericidal than

the antistaphylococcal β-lactams (e.g., nafcillin

or cefazolin) and may be less efficacious

CARBAPENEMS

IMIPENEM

Disrupts bacterial cell wall synthesis

Very resistant to hydrolysis by most β-lactamases

Excellent activity for aerobes and anaerobes

Streptococci including penicillin-resistant S. pneumoniae

Enterococci excluding E. faecium and non-β-lactamase-producing penicillin-resistant strains

Staphylococci including penicillinase-producing Not methicillin-resistant staphylococci

Listeria

Enterobacteriaceae including organisms that are cephalosporin-resistant by virtue of expression of

extended spectrum β-lactamases Pseudomonas and Acinetobacter most strains are inhibited

Anaerobes including B. fragilis

Therapeutic Uses Wide variety of infections including:

urinary tract

lower respiratory

intra-abdominal and gynecological

skin and soft tissue

bone and joint

Imipenem should not be used as monotherapy for infections with P. aeruginosa because of the risk of developing resistance during therapy

MEROPENEM

Not sensitive to renal dipeptidase

Toxicity and clinical efficacy are similar to

imipenem except that it may be less likely to

cause seizures

Clinical experience with meropenem

demonstrates therapeutic equivalence with

imipenem

ERTAPENEM Differs from imipenem and meropenem by having a

longer serum t1/2

Once-daily dosing

Inferior activity against P. aeruginosa and Acinetobacter spp.

Activity against gram-positive, Enterobacteriaceae, and anaerobes makes it attractive for use in intra-abdominal and pelvic infections

AZTREONAM

Monocyclic β-lactam

Resistant to β-lactamases elaborated by most gram-negative bacteria

Antimicrobial activity differs from other β-lactams and resembles that of

Aminoglycosides

Activity only against gram-negative bacteria

No activity against gram-positive bacteria and anaerobes

Activity against Enterobacteriaceae is excellent, as is that against P. aeruginosa

Highly active against H. influenzae and gonococci

Administered IM or IV

POLYMYXIN B & COLISTIN

Polymixins are group antibiotics elaborated by various

strains of Bacillus polymyxa

Colistin is produced by Bacillus colistinus

Cationic detergents

Colistin (polymyxin E) is available as colistin sulfate for

oral use and as colistimethate sodium for parenteral

administration

Antimicrobial activities Polymyxin B and colistin are restricted to gram-negative

bacteria

Are not absorbed orally and poorly absorbed from mucous membranes and burn surfaces

They are cleared renally

Polymyxin B sulfate is available for ophthalmic, otic, and topical use

Colistin may be useful as a salvage regimen for infections caused by multiple-drug-resistant organisms