Treatment of sexually transmitted infections (STIs)

Objectives
At the end of this class , students should be familiar with:
1. General Recommendations for STD Treatment and Follow-Up 2. The right selection of antimicrobial Therapy of Sexually Transmitted

Diseases (STD) according to type of infection and patient status

3. Causes of resistance to antimicrobial agents used for STIs 4. Classes and side effects of antimicrobial agents commonly used for SIDs

General Recommendations for STD Treatment and Follow-Up

When treating patients for STDs in the ED, it is important to remember that: A. Many STDs occur together B. Follow-up and compliance are poor C. Lack of treatment can contribute to infertility. For these reasons, a standardized approach is suggested for patients with suspected STDs. This should include: 1. Treating even when an STD is only suspected, especially for gonorrhea and chlamydia, with emphasis on single-dose treatments that are administered in the ED 2. Ascertaining pregnancy status and consulting obstetrians if the patient is pregnant 3. Obtaining a serologic test for syphilis 4. Reporting appropriate diseases to the city health department 5. 6. 7. 8. Providing counseling for STD prevention and HIV testing Advising partner to seek treatment Arranging for appropriate follow-up Documenting treatment, counseling, and follow-up on the medical record

Therapy of Sexually Transmitted Diseases (STD)

Disease
Chlamydia Uncomplicated infections in adults/adolescents Azithromycin (single dose) or Doxycycline 1 g po Erythromycin 500 mg po qid x 7 d or Ofloxacin 300 mg po bid x 7 d

Recommended Regimens

Dose/Route Alternative Regimens

100 mg po bid x7d

Pregnant women

Amoxicillin or
Azithromycin or

500 mg po tid x 7d
1 g po

Erythromycin 250 mg po qid x 14 d

Therapy of Sexually Transmitted Diseases (STD)

Disease
Gonorrhea Uncomplicated infections in adults/adolescents Ceftriaxone or Cefixime plus a Chlamydia recommended regimen 125 mg IM 400 mg po Ceftizoxime 500 mg IM or Cefotaxime 500 mg IM or Cefoxitin 2 g IM plus probenecid 1 g po or Spectinomycin 2 g IM plus a Chlamydia recommended regimen Spectinomycin 2g IM plus a Chlamydia recommended regimen

Recommended Regimens

Dose/ Route

Alternative Regimens

Pregnant women

Ceftriaxone or Cefixime plus a Chlamydia recommended regimen

125 mg IM 400 mg po

Therapy of Sexually Transmitted Diseases (STD)

Pelvic inflammatory disease Parenteral
Cefotetan or
2 g IV q 12 h 2 g IV q 6 h 100 mg po or IM q 12 h 900 mg IV q 8 h 2 mg/kg IV or IM followed by 1.5 mg/kg IV or IM q 8 h 250 mg IM 2 g IM 1 g po

Parenteral Ampicillin/sulbactam 3 g IV q 6 h plus Doxycycline 100 mg po or IV q 12 h

If parenteral cephalosporin therapy is not feasible, use of fluoroquinolone (levofloxacin 500mg orally once daily or ofloxacin 400 mg twice daily for 14 days) with or without metronidazole ( 500mg orally twice daily for 14 days) may be considered if the community prevalence and individual risk of gonorrhea is low. Tests for gonorrhea must be performed prior to instituting therapy and the patient managed as follows: If NAAT test is positive, parenteral cephalosporin is recommended. If culture for gonorrhea is positive, treatment should be based on results of antimicrobial susceptibility. If isolate is quinolone-resistant or antimicrobial susceptibility cannot be assessed, parenteral cephalosporin is recommended.

Cefoxitin plus Doxycycline or

Clindamycin plus Gentamicin

Ceftriaxone or Cefoxitin with Probenecid plus Doxycycline

100 mg po bid x 14d

500 mg bid x 14 d

Metronidazole

Therapy of Sexually Transmitted Diseases (STD)

Nongonococcal Cervicitis

Azithromycin or
Doxycycline

1 g po
100 mg po bid x 7 d

Erythromycin 500 mg po qid x 7d or Ofloxacin 300 mg po bid x 7 d or Levofloxacin 500 mg po qd x 7d Erythromycin 500 mg po qid x 7d or Ofloxacin 300 mg po bid x 7 d or Levofloxacin 500 mg po qd x 7d

Nongonococcal urethritis

Azithromycin or
Doxycycline

1 g po
100 mg po bid x 7 d

Therapy of Sexually Transmitted Diseases (STD)

Epididymitis

Ceftriaxone plus Doxycycline For acute epididymitis most likely caused by enteric organisms or with negative gonococcal culture Ofloxacin

250 mg IM 100 mg po bid x 10 d

Levofloxacin 500 mg po pd x 10 d

300 mg orally twice a day for 10 days

Therapy of Sexually Transmitted Diseases (STD)

Trichomoniasis

Therapy of Sexually Transmitted Diseases (STD)

Disease

Recommended Dose/ Regimens Route

Alternative Regimens

Syphilis

Primary, secondary, and early latent Late latent and unknown duration Neurosyphilis

Benzathine penicillin G

2.4 million units IM

Doxycycline 100 mg po bid x 2 weeks or Tetracycline 500 mg po qid x 2 weeks Doxycycline 100 mg po bid x 4 weeks or Tetracycline 500mg po qid x 4 weeks Procaine penicillin G, 2.4 million units IM qd x 1410 d plus Probenecid 500 mg po qid x 1410d Ceftriaxone 2 g IM or IV qd x10 14d, (desensitization if penicillin allergic)

Benzathine penicillin G

7.2 million units, administered as 3 doses of 2.4 million units IM, at 1 week intervals 1824 million units daily, administered as 3 4 million units IV q 4 h x 1410d

Aqueous crystalline penicillin G

Therapy of Sexually Transmitted Diseases (STD)

Disease
Syphilis Pregnant women

Recommende d Regimens

Dose/ Route

Alternative Regimens

Primary, secondary, and early latent

Late latent and unknown duration

Benzathine penicillin G

2.4 million units IM

None

Benzathine penicillin G

7.2 million units, administered as 3 doses of 2.4 million units IM, at 1 week intervals

None

Therapy of Sexually Transmitted Diseases (STD)

Disease
Syphilis Congenital syphilis

Recommended Regimens
Procaine penicillin G

Dose/ Route
50,000 U/kg IM daily for 1014 d

Alternative Regimens

Aqueous crystalline penicillin G 100,000150,000 U/kg/day in doses of 50,000 U/kg IV q 12 h for 7 days then q 8 h for 37 days

Children: early (primary) Children: late latent or >1 y late

Benzathine penicillin G Benzathine penicillin G

50,000 U/kg IM once (max. 2.4 million units) 50,000 U/kg IM for 3 doses at 1 week intervals, to max. total dose of 7.2 million units

Therapy of Sexually Transmitted Diseases (STD)

Disease
Syphilis HIV infection

Recommended Regimens
The same

Dose/ Route

Alternative Regimens

Primary, secondary, and early latent

Late latent and unknown duration 15 with normal CSF examination Neurosyp hilis

Benzathine penicillin G

2.4 million units IM

The efficacy of nonpenicillin regimens in HIV-infected persons has not been well studied
None

Benzathine penicillin G

7.2 million units, administered as 3 doses of 2.4 million units IM, at 1 week intervals

Aqueous crystalline penicillin G

1824 million units daily, administered as 34 million units IV q 4 h x 1410d

Procaine penicillin G, 2.4 million units IM qd x 1410 d plus Probenecid 500 mg po qid x 1410d (desensit. For pencillin if allerg

Therapy of Sexually Transmitted Diseases (STD) Lymphogranuloma venereum (LGV):

Therapy of Sexually Transmitted Diseases (STD) Granuloma inguinale:

Therapy of Sexually Transmitted Diseases (STD) Herpes simplex virus:

Therapy of Sexually Transmitted Diseases (STD)

Candida albicans (vulvovaginal candidiasis):

Therapy of Sexually Transmitted Diseases (STD) Candida albicans (vulvovaginal candidiasis):

Macrolides

Macrolide antibiotics
Antibiotics in this group include
Erythromycin (Robimycin),

Clarithromycin (Biaxin),
Azithromycin (Zithromax),

Macrolide antibiotics
Azithromycin
Spectrum Specturm of activity and clinical uses are identical to those of clarithromycin

It is active against M.avium and T. gondii.

Azithromycin is slightly less active than erythromycin and clarithromycin against Staphylococci and sterptococci and slightly more active against H. influenzae.

Azithromycin is highly active against chlamydia.

Macrolide antibiotics
Adverse Effects
- Mild gastrointestinal upset with nausea, diarrhea,and abdominal pain. - Rashes are seen infrequently.

- Thrombophlebitis and transient impairment of hearing may follow I.V dministration. - Cholestatic hepatitis may occur when drug therapy lasts longer than 10 days or

repeated courses are prescribed.

- Erythromycin and derivatives inhibit hepatic microsomal enzymes and interfere with

the actions of various drugs, including theophylline and carbamazepine .

Macrolide antibiotics
Azithromycin
Kinetics Azithromycin differs from erythromycin and clarithromycin mainly in pharmacokinetic properties. A 500 mg dose of azithromycin produces relatively low serum concentrations around 0.4mcg/ml. however azithromycin penetrates into most tissues (except CSF) and phagocytic cells extremely well, with tissue concentrations exceeding serum conc. by 10- to 100-fold.

The Drug is slowly released from tissues (tissue t1/2 of 2-4 days).
These unique properties permit once-daily dosing and shortening of the duration of treatment in many cases. A single 1-g dose of azithromycin is as effective as a 7-day course of doxycycline for Chlamydial cervisitis and urethritis

Macrolide antibiotics
Adverse Effects -Azithromycin is rapidly absorbed and well tolerated orally and well-tolerated. -It should be administered 1 hour before or 2 hours after meals. -Aluminium and magnesium antacids do not alter bioavailability but delay absorption And reduce peak serum concentrations. Because it differes in chemical structure, azithromycin does not inactivate cytochrome P450 enzyme and therefore is free of the drug interactions that occur with erythromycin and clarithromycin

Inhibitors of Nucleic Acid Synthesis

Quinolones
Classification according to Spectrum

First Generation: Nalidixic Acid Second Generation: Cipro-, Nor-, Ofloxacin Third Generation: Levo-, Moxi-, Sparfloxacin Fourth Generation: Trovafloxacin

Quinolones
The quinolones are contraindicated in pregnant and nursing
women, and children younger than 18 y of age.

Fluoroquinolones lack activity for Treponema pallidum but have activity against N. gonorrhoeae, C. trachomatis, and H. ducreyi.

Numerous Pathogens, including S. aureus, enterococci, P. aeruginosa, and Streptococcus pyogenes now exhibit resistance worldwide.

Mechanism Of Action

Topoisomerase II

Topoisomerase IV

Pharmacokinetics

Quinolones
Spectrum

Quinolones
Therapeutic Uses Urinary Tract Infections Gonorrheal infections & Chlamydial cervicitis & urethritis Diarrhoea caused by E.coli Typhoid fever Intra-abdominal infections Infections of bones & joints Resistant TB

Quinolones
Adverse effects (mainly tendons and cartilages): - Spontaneous tendon ruptures or damage, especially with the concurrent use of a systemic corticosteroids - Peripheral neuropathy : Quinolones should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness and or weakness -Phototoxicity

-Prolonged QT Interval: moxifloxacin.

-Second generation drugs are hepatic microsomal enzyme inhibitors

Quinolones
Adverse Effects

Quinolones
Interactions

Quinolones
Resistance

Altered Target (mutations) Decreased Accumulation (p-glycoprotein)

Quinolones
Contraindications Pregnancy Lactation Patients under 18 years of age

Antimicrobial Drugs Cell wall Inhibitors

Cell wall Inhibitors

Cell wall Inhibitors- Penicillins

Mechanism of Action

Cell wall

Cell wall Inhibitors- Penicillins

Spectrum of Natural Penicillin G

Cell wall Inhibitors- Penicillins

Antistaphylococcal penicillins
Methicillin, nafcillin, oxacilli, and dicloxacillin are penicillinase-resistant penicillins. Their use is restricted to the treatment of infections caused by penicillinaseproducing staphylococci. Because of its toxicity, methicillin is not used clinically except to identify resistant strains of S. aureus. Currently a serious source of nosocomial (hospitalacquired) infections, MRSA is usually susceptible to vancomycin and, rarely, to ciprofloxacin or rifampin.

Cell wall Inhibitors- Penicillins

Spectrum of extended-spectrum Penicillin (e.g. ampicillin & amoxicillin)

Cell wall Inhibitors- Penicillins

Anti-pseudomonal Penicillins (e.g. Carbenicillin, ticarcillin & piperacillin)

Cell wall Inhibitors- Penicillins

Anti-pseudomonal Penicillins (e.g. Carbenicillin, ticarcillin & piperacillin)

Cell wall Inhibitors- Penicillins

Penicillins & Aminoglycosides: The antibacterial effects of all the -lactam antibiotics are synergistic with the aminoglycosides. Because cell wall synthesis inhibitors alter the permeability of bacterial cells, these drugs can facilitate the entry of other antibiotics (such as aminoglycosides) that might not ordinarily gain access to intracellular target sites. This can result in enhanced antimicrobial activity.
Although the combination of a penicillin plus an aminoglycoside is used clinically, these drug types should never be placed in the same infusion fluid, because on prolonged contact, the positively charged aminoglycosides form an inactive complex with the negatively charged penicillins.

Cell wall InhibitorsPenicillins

Cell wall Inhibitors- Penicillins

Cell wall Inhibitors- Penicillins

Adverse Effects

Benzathine benzylpenicillin(benzathine penicillin)

A form of penicillin that is slowly absorbed into the circulation, after IM injection ,and hydrolysed to benzylpenicillin in vivo.

It is the drug-of-choice when prolonged low concentrations of benzylpenicillin are required and appropriate, allowing prolonged antibiotic action over 24 weeks after a single IM dose. Specific indications for benzathine penicillin include: Prophylaxis of rheumatic fever Early or latent syphilis

Adverse Effetcs of penicillins

Allergy - 5% Anaphylaxis - rare Diarrhea: caused by a disruption of the normal balance of intestinal microorganisms, is a common problem. Pseudomembranous colitis (Clostridium difficile) Leucopenia Thrombocytopenia (low platelet count) Coombs positive hemolytic anaemia .

Resistance to penicillins
a. Intrinsic resistance in organisms that either lack a peptidoglycan cell wall (for example, Mycoplasma) or that have cell walls that are impermeable to the drugs.

b. Acquired resistance to the penicillins by plasmid transfer has become a significant clinical
problem. By obtaining a resistance plasmid, bacteria may acquire one or both of the following properties 1. -Iactamase activity: Enzymes hydrolyze the cyclic amide bond of the -Iactam ring, which results in loss of bactericidal activity. -Lactamases are either constitutive or are acquired by the transfer of plasmids. 2. Decreased permeability to drug: prevents the drug from reaching the target penicillin-binding proteins (PBPs). 3. Altered penicillin binding proteins

II. Cephalosporins
Cephalosporins

II. Cephalosporins
Adverse effects Allergic manifestations: The cephalosporins should be avoided or used with caution in individuals allergic to penicillins (cross-sensitivity).

A disulfiram-like effect:
When cefamandole or cefoperazone is ingested with alcohol or alcohol-containing medications, a disulfiram-like effect is seen, because these cephalosporins block the second step in alcohol oxidation, which results in the accumulation of acetaldehyde.

Bleeding: Bleeding can occur with

cefamandole or cefoperazone, because of anti-vitamin K effects; administration of the vitamin corrects the problem.

Tetracyclines
Because of resistance, doxycycline no longer is recommended for

gonococcal infections.
Contraindicated for pregnant and nursing women.

Bacteria may become resistant to tetracyclines by blocking the

entry of the compound in the cell by interfering with the passive

or active transport system.

Resistance is mainly plasmid mediated.

Tetracyclines
Adverse Effects
- Gastrointestinal side effects (nausea, vomiting and diarrhea) Modification of the intestinal flora and allow for the unsuppressed multiplication of organism like Pseudomonas, Proteus, staphylococci, Clostridia and Candida. This can lead from stomach upset to full-blown enterocolitis . - Tetracylines are bound to growing bone and teeth as a result of chelation with calcium. - Tetracyclines can cross the placenta and if given during pregnancy the drug may cause enamel dysplasia with discoloration, and bone deposits with growth inhibition in the fetus. - Tetracyclines can precipitate hepatic dysfunction (even hepatic necrosis), especially during pregnancy. - IM injections cause pain and irritation and should be avoided .