Antimicrobials 3

• Fluoroquinolones


  • Broad-spectrum agents with multiple applications
  • Disrupt DNA replication and cell division
  • Do not disrupt synthesis of proteins of cell wall
  • Can be administered orally or IV
  • Resistance develops slowly but has become common in Neisseria gonorrhoeae
• Ciprofloxacin


  • Broad-spectrum antibiotic (gram-negative and some gram-positive organisms)
  • Inhibits bacterial DNA gyrase and topoisomerase II (needed for DNA replication and cell division)
  • Drug of choice for anthrax
  • Used for infections in respiratory, urinary tract (UTI), GI, bones, joints, skin, and soft tissue
  • Not good choice for staphylococcal infections
  • Not useful for anaerobes
• Adverse effects of Ciprofloxacin

  • GI: Nausea/vomiting, diarrhea, abdominal pain
  • Central nervous system (CNS): Dizziness, headache, restlessness, confusion, rarely seizures
  • Tendon rupture (Achiles)
  • Phototoxicity
  • Candida infections: Pharynx and vagina
  • Increased risk of Clostridium difficile infection (CDI)
• Adverse effects of Ciprofloxacin in older adult patients

  • Confusion, somnolence, psychosis, visual disturbances
  • Myasthenia gravis
  • Increase risk for aortic dissection or ruptured abdominal aortic aneurysm
• Highest risk for adverse effects of Ciprofloxacin is in patients >60, taking glucocorticoids, or gone organ transplant
• Ciprofloxacin can exacerbate muscle weakness in patients with Myasthenia Gravis
• Compounds that reduce absorption of Ciprofloxacin

  • Aluminum antacids
  • Magnesium antacids
  • Iron salts
  • Zinc salts
  • Sucralfate
  • Milk and dairy products that contain Ca2
  • Calcium supplements
• Cationic compounds should be administered 6 hours before or 2 hours after Ciprofloxacin
• Drugs that can have elevated levels with Ciprofloxacin

  • Theophylline (used for asthma)
  • Warfarin (an anticoagulant)
  • Tinidazole (an antifungal drug)
• Ofloxacin


  Indications: Respiratory, Urinary tract, GI, skin and soft tissue infections
• Moxifloxacin


  • Indications: Respiratory tract, Urinary tract, intra-abdominal infections, and skin and skin structure infections
  • Can cause QT prolongation
• Norfloxacin is no longer available in the US
• Levofloxacin


  Indications: Respiratory tract, urinary tract, GI, and skin and skin structure infections
• Gemifloxacin


  • Indications: Respiratory for CAP and bronchitis
  • Can cause QT prolongation
• Delafloxacin


  Indications: Infections of skin and skin structures
• Lefamulin (Xenleta)


  • Inhibits bacterial protein synthesis
  • Indications: Treatment of community-acquired bacterial pneumonia caused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, Chamydophila pneumoniae
• Moxifloxacin is just as effective as Lefamulin for community-acquired pneumonia but has fewer side effects and costs $25 for oral administration
• Lefamulin can cause QT prolongation
• Metronidazole [Flagyl]


  • Bactericidal - anaerobic only
  • Must be taken up by cells and converted into active form, which interacts with DNA causing strand breakage and loss of helical structure, inhibiting nucleic acid synthesis and leading to cell death
  • Uses: Protozoal infections, infections caused by obligate anaerobes, Helicobacter pylori, Clostridium difficile, Bacteroids fragilis, Gardnerella vaginalis, Peptococcus species/peptostreptococcus, infections involving aerobic bacteria (must include a drug active against them), prophylaxis for surgery with high risk infection of anaerobes
• Adverse effects of Metronidazole

  • Neurotoxicity
  • Allergy
  • Superinfections
  • Disulfuram like reaction with alcohol
• There is a black box warning for Metronidazole due to carcinogenic risk in mice and rats
• Daptomycin [Cubicin]


  • Cyclic lipopeptide (new class)
  • Kills virtually all gram-positive bacteria, including methicillin-resistant S. aureus (MRSA)
  • Use: Bloodstream infection with S. aureus, and complicated skin and skin structure infections caused by susceptible strains of gram-positive bacteria
  • No significant drug interactions, but should avoid taking with statins
  • Adverse effects: Possible muscle injury, myopathy
  • Given only once daily IV, no laboratory work needed
• Chancroid


  • Caused by Hemophilus ducreyi, a gram-negative bacillus
  • Prevalence: Endemic in many areas of the US, must be part of differential diagnosis for genital ulcers, high rate of HIV identified among individuals presenting with chancroid, estimated up to 10% of patients are also infected with syphilis and HSV
  • Symptoms: Women usually asymptomatic, men have single or multiple superficial painful ulcers surrounded by an erythematous halo, ulcers may be necrotic or severely erosive
  • Diagnosis: Usually a matter of exclusion, involves genitalia and unilateral abscess formation or both, definitive diagnosis is made morphologically (sensitivity no > 80%)
  • Treatment: Azithromycin 1 gram PO x1, Ceftriaxone 250 mg IM x1, Ciprofloxacin 500 mg PO BID, Erythromycin 500 mg PO TID for 7 days
• Chlamydia


  • A parasitic STD caused by Chlamydia trachomatis that produces serious reproductive tract complications in either sex
  • Incidence: Most common bacterial sexually transmitted disease in the US, over 4 million new infections annually
  • Symptoms: Females often asymptomatic, may have dysuria, intramenstrual spotting, postcoital bleeding, dyspareunia, vaginal discharge; Males often asymptomatic, may have dysuria, thick cloudy penile discharge, testicular pain
  • Diagnosis: Nucleic acid amplification test (NAAT) considered gold standard, antigen detection via swab or urine has 80-95% sensitivity compared to culture
  • Management: Uncomplicated - Doxycycline 100 mg PO BID x7 days, Azithromycin 1 gram PO single dose, Levofloxacin 500 mg PO x7 days; Complicated - Doxycycline 10-14 days if epididymis involved or for pelvic inflammatory disease; Second-line - Levofloxacin 500 mg PO daily x7 days, Ofloxacin 300 mg PO BID x7 days; Erythromycin 500 mg PO QID x7 days if unable to take doxycycline; Pregnancy - Amoxicillin 500 mg PO TID x7 days; Children - Erythromycin base 50 mg/kg/day PO divided 4 doses x14 days if <45 kg, Azithromycin 20 mg/kg/day PO x3 days if ≥45 kg and <8 years, Azithromycin or Doxycycline if ≥8 years
• Genital Warts


  • Caused by human papillomavirus (HPV), the most common sexually transmitted infection in the US
  • Warts in anogenital or genital area, often asymptomatic
  • HPV types 6 and 11 most commonly cause genital warts, have low oncogenic potential
  • HPV types 16, 18, 31, 33, 35, 39, 45, 52, 55, 56, and 58 have the highest oncogenic potential for anogenital carcinoma
  • Infection transmitted through direct contact, 10-30% of cases resolve spontaneously
  • Oral HPV infection is a common cause of oropharyngeal cancer
  • Diagnosis based on clinical findings, acetowhitening can make subclinical lesions visible but is not diagnostic
  • Prevention: Use of condoms provides limited protection, HPV vaccination, screen for other STDs, circumcision of men may prevent transmission and acquisition
  • Treatment: Provider treatments include podophyllin resin, trichloroacetic acid, cryotherapy, surgical excision, electrodessication, laser treatment; Self-treatment options include imiquimod, podofilox, sinecatechins
• Gonorrhea


  Caused by Neisseria gonorrhoeae, a gram-negative, intracellular aerobic diplococcus that produces purulent inflammation of mucous membranes and is perinatally transmitted from an infected mother to her newborn during delivery
• Treatment options for external warts

  • Imiquimod 3.75% or 5% cream (Aldara) applied three times weekly until resolution or up to 16wk; leave on for 6-10 hr before washing off
  • Podofilox 0.5% gel or solution (Condylox) applied BIDfor 3 days, off 4 days; mayrepeat every wk for 1-4 wk
  • Sinecatechins 15% ointment (Veregen) applied TID for up to 16 wk
• Cervical warts


  Refer to specialist for biopsy prior to treatment
• Treatment options for vaginal warts

  • TCA or BCA 80-90%
  • Cryotherapy of vagina is not recommended due to risk of fistula formation
• Treatment options for anal warts

  • Cryotherapy
  • TCA or BCA 80-90%
  • Podofilox 0.5% gel or solution (Condylox) applied BIDfor 3 days, off 4 days; may repeat every wk for 1-4 wk
• Neisseria gonorrhoeae


  Gram-negative, intracellular aerobic diplococcus that causes a sexually transmitted disease (STD)
• Gonorrhea


  • Produces purulent inflammation of mucous membranes
  • Perinatally transmitted from an infected mother to her newborn during delivery
  • Can be asymptomatic in early infection, especially among women
  • Untreated gonorrhea infection can cause significant complications
  • N. gonorrhoeae that are resistant to antibiotics have been increasing worldwide
• Modes of transmission for gonorrhea

  • Sexual contact
  • Vertical transmission from infected mother to infant during childbirth
  • Penile-rectal contact
• Risk factors for gonorrhea

  • Sexual exposure to an infected partner without barrier protection (e.g., failure to use a condom or condom failure)
  • ANY new sex partners
  • More than one sex partner
  • Sex with a partner who has concurrent partners
  • Sex with a partner who has an STD
  • Recent gonococcal infection: due to reinfection from untreated partner
  • Infant born to infected mother
  • Increased risk of PID with intrauterine device/system
• Symptoms of gonorrhea in men

  • Urethritis: purulent urethral discharge; blood-tinged
  • Dysuria
  • Penile edema
  • Acute epididymitis: testicular pain (unilateral)
  • Prostatitis: decreased stream, trouble initiating urine flow, frequency, painful ejaculation
• Symptoms of gonorrhea in women

  • Endocervical/vaginal discharge: thin, purulent, and mildly odorous; usually minimal
  • Dysuria
  • Intermenstrual/abnormal bleeding
  • Dyspareunia
  • Bartholin's gland abscess
  • Symptoms of rectal infection (40% of infected women have rectal infection)
  • Symptoms of pelvic inflammatory disease (PID): abdominal pain, cervical motion tenderness, adnexal tenderness, or pain/fever
• Symptoms of gonorrhea in both sexes

  • Rectal infection: rectal discharge, tenesmus, rectal burning or itching
  • Pharyngeal infection: exudative pharyngitis, cervical lymphadenopathy
  • Conjunctiva infection: purulent discharge from eye (usually unilateral)
• Symptoms of gonorrhea in neonates

  • Bilateral conjunctivitis (ophthalmia neonatorum): eye pain, redness, purulent discharge (usually bilateral)
  • Scalp infection at site of fetal monitoring, electrodes
  • Disseminated gonococcal infection (DGI) with sepsis, arthritis, meningitis
• Nucleic-acid amplification test (NAAT)


  Gold standard diagnostic test for gonorrhea using urine sample
• Gram stain of discharge smear


  Shows gram-negative diplococci and WBC