Kingdom of Bahrain Arabian Gulf University College of Medicine and Medical Sciences

1. Kingdom of BahrainArabian Gulf UniversityCollege of Medicine and Medical Sciences Internal Medicine Notes Infectious Diseases Prepared by: Ali JassimAlhashli Based on: Kaplan Step 2 CK Internal Medicine

2. Introduction to Antibiotics • Semisyntheticpenicillins (anti-staphylococcal penicillins): • Examples: oxacillin, naficillin, cloxacillin and decloxacillin. • They are effective against STAPHYLOCOCCI and STREPTOCOCCI. • If organism is methicillin-sensitive: use anti-staphylococcal penicillins (examples mentioned above). • If organism is methicillin-resistant (MRSA): use vancomycin. Linezolid is an alternative for vancomycin. • Penicillin G, penicillin VK, ampicillin and amoxicillin: • They are effective against STREPTOCOCCI (S.pneumoniae, S.pyogens and viridans group) but not against staphylococcus. • Amoxicillin becomes effective against Staphylococcus when combined with clavulanic acid (Augmentin). • All of these agents are effective against gram-negative bacteria such as Neisseria. • 1st and 2nd generations of cephalosporins: • Both of them have the same coverage of semisyntheticpenicillins against STAPHYLOCOCCI and STREPTOCOCCI. • 1st generation cephalosporins: • Examples: cefadroxil, cefazolin and cephalexin. • They are also effective against gram-negative organisms: E.coli and Moraxella. • 2nd generation cephalosporins: • Examples: cefotetan, cefuroxime and cefoxitin. • They have the same coverage of 1st generation cephalosporins in addition to: Klebsiella, Hemophilus and Proteus. • Allergic cross-reactivity with penicillins: • If a patient has an allergy to penicillins described as a RASH ONLY → you can use cephalosporins. • If a patient has an allergy to penicillins described as ANAPHYLAXIS → you cannot use cephalosporins. Alternatives are: • Minor infections: macrolides (azithromycin or clarithromycin) of fluoroquinolones (levofloxacin). • life-threatening infections: vancomycin or linezolid.

3. Antibiotics against gram-negative bacilli: • Penicillins: • Examples: piperacillin and ticarcillin. • They are covering Enterobacteriaceae (such as E.coli, Proteus and Klebsiella) + PSEUDOMONAS • Piperacillin/tazobatum also covers STAPHYLOCOCCI. • 3rd and 4th generations of cephalosporins: • 3rd generation: ceftriaxone and ceftazidime. • 4th generation: cefepime. • ONLY CEFTAZIDIME AND CEFEPIME WILL COVER PSEUDOMONAS. • Quinolones: • Examples: ciprofloxacin and levofloxacin. • They cover most of Enterobacteriaceae (such as E.coli, Proteus, Hemophilus, Morexella and Klebsiella). • ONLY CIPROFLOXACIN WILL COVER PSEUDOMONAS. • Aminoglycosides: • Examples: gentamicin, amikacin and tobramycin. • Carbapenems: • Examples: imipenem, meropenem and ertapenem. • They have coverage against ENTEROBACTERIACEAE, PSEUDOMONAS, STAPHYLOCOCCI and ANAEROBES. • NOTICE THAT ERTAPENEM WILL NOT COVER PSEUDOMONAS. • Anaerobes: metronidazole is your choice. Also, It is the drug for choice in treating Clostridium defficile. Introduction to Antibiotics

4. Definition: it is inflammation/infection of meninges which are covering the CNS (brain and spinal cord). • Etiology: • Notice that the most common cause of meningitis is VIRAL INFECTION (aseptic meningitis):entero-viruses, arboviruses, HIV and Herpes Simplex Virus (HSV). • Bacterial meningitis (classified according to age groups): • Neonates: S.agalactiae and Listeriamonocytogens. • Adolescents: Neisseriameningitidis (most common and transmitted through respiratory droplets), S.pneumoniae and H.influenzae (not common nowadays due to vaccination). • Adults: S.pneumoniae (most common) and Neisseriameningitidis. • Elderly: S.pneumoniae and Listeriamonocytogens. • Notice that S.pneumoniae is the most common cause of bacterial meningitidisbeyong neonatal period. • Listeriamonocytogens is common in very young (neonates) and very old (elderly) group (because they are immunocompromised). • S.aureus is more common in those with recent neurosurgery due to instrumentation which will introduce the organism from the skin into the CNS. • Cryptococcus is more common in those with HIV and CD4 count > 100 cells/mm3. • Transmission of the infection to CNS: • From local infection: otitis media, sinusitis and dental infections. • Hematogenous spread: commonly from endocarditis or pneumonia. • Clinical presentation: • Fever. • Headache. • Photophobia. • Nausea and vomiting. • Positive meningeal signs (neck rigidity, Kernig’s and Brudzinski’s signs). • Presence of rash is suggestive of infection with Neisseriameningitidis. Meningitis

5. Meningitis

6. Diagnosis: • When a patient presents to the emergency with clinical manifestations suggesting meningitis (mentioned previously), you have to exclude the presence of intracranial pressure (by fundoscopy to look for papilledema or CT-scan of the head) because lumbar puncture will be contraindicated in patient with increased intracranial pressure (herniation of brainstem and respiratory arrest). • If intracranial pressure is normal, do lumbar puncture and obtain a sample for CSF analysis. If lumbar puncture will be delayed < 30 minutes, start empiric antibiotic therapy. • CSF analysis for bacterial meningitis will show: • ↑WBCs predominantly neutrophils. • ↓glucose. • ↑proteins. • Most specific test being CSF culture. • CSF analysis for viral or TB meningitis will show: ↑WBCs predominantly lymphocytes. • Treatment: • Administer dexamethasone 15 minutes before initiating your empiric antibiotics (because it decreases mortality and deafness). Continue dexamethasone for 4 days if bacterial meningitis is confirmed. If patient has aseptic meningitis, discontinue dexamethasone. • Empiric therapy: vancomycin + ceftriaxone (add ampicillin in neonates and elderly to cover Listeria). Meningitis

7. Meningitis Papilledema CT-scan showing increased intracranial pressure

8. Encephalitis: • Definition: infection of the brain (it includes: meninges + brain parenchyma). • Etiology: most cases are due to viruses (most common virus is Herpes Simplex type-1 which is affecting temporal lobes). • Clinical manifestations: fever, headache + ALTERED MENTAL STATUS. Neck rigidity might also be present. • Diagnosis: • CT/MRI of the head. • Key to diagnosis is lumbar puncture with PCR of CSF for HSV. • Treatment: • IV acyclovir. • Acyclovir-resistant cases: foscarent. • Brain abscess: • Definition: it is a collection of infected material within the brain parenchyma. • Etiology: • HIV-positive patient with CD4 count > 100 cells/mm3 → toxoplasmosis. • In HIV-negative patients → brain abscess is usually polymicrobial (although Streptococci are responsible in 60% of cases). • Clinical presentation: • Initially, patient might present with a focal neurologic deficit and he might develop seizure. • Headache is the most common symptom. • Fever might also occur. • Diagnosis: • Contrast CT-scan of the head: enhancement of the lesion with formation of a ring around it. • Most accurate: MRI. • Treatment: • HIV-positive patients with suspected cerebral toxoplasmosis: pyrimethamine and sulfadiazine for 10-14 days. • HIV-negative patients: • Sterotactic aspiration of the abscess. • Combination therapy: penicillin, metronidazole and 3rd generation cephalosporin. Encephalitis and Brain Abscess

9. Encephalitis and Brain Abscess MRI showing herpes simplex encephalitis CT-scan showing brain abscess

10. Otitis media: • Definition: it is infection/inflammation of the middle ear cavity between Eustachian tube and the tympanic membrane. • Etiology: • S.pneumoniae. • H.influenzae. • Morexellacatarrhalis. Rest of cases are viral. • Clinical manifestations: fever, ear pain and decreased hearing. • Diagnosis: • Otoscope: red, bulging tympanic membrane with loss of light reflex. • Pneumatic otoscope: immobility of tympanic membrane with insufflation of air. • Treatment: • Initial: amoxicillin. If patient is not responding → amoxicillin/ clavulanic acid. • If patient has severe allergy to penicillin (anaphylaxis) → macrolides (azithromycin or clarithromycin). • Sinusitis: • Definition: infection/inflammation of sinuses, most commonly maxillary followed by ethmoidal, frontal and sphenoidal. • Etiology: • Most cases are due to viruses. • Bacterial causes: S.pneumoniae, H.influenzae and Morexellacatarrhalis. • Clinical manifestations: headache (which becomes worse when leaning forward), facial pain and purulent nasal discharge. Fever occurs in 50% of cases. • Diagnosis: clinically but can be confirmed with CT-scan of sinuses. • Treatment: • Viral cases resolve within 7-10 days with the use of NSAIDs, anti-histamines and decongestants. • Bacterial cases: start with amoxicillin. If patient is not responding → amoxicillin/ clavulanic acid. If patient has severe allergy to penicillins (anaphylaxis) → use macrolides (azithromycin or clarithromycin). Otitis Media and Sinusitis

11. Otitis Media and Sinusitis

12. Pharyngitis: • Definition: infection/inflammation of the pharynx. • Etiology: • Majority of cases are due to viruses (example: EBV). • Most common bacterial organism is Group A Beta Hemolytic Streptococci GABHS (S.pyogens). • Clinical manifestations: • Sore throat and inflammation of the pharynx. • Cervical adenopathy. • Exudative covering suggests infection with S.pyogens. • Diagnosis: serology to detect Streptococcal antigen. • Treatment: penicillins. • Influenza: • Definition/etiology: it is a systemic viral illness which is caused by influenza A or B infections. they are transmitted through respiratory droplets. Influenza can lead to: otitis media, sinusitis, bonrchitis and pneumonia. • Clinical manifestations: • Systemic manifestations: low-grade fever, fatigue, myalgias and headache. • Upper respiratory symptoms: rhinorrhea, non-productive cough and sore throat. • Diagnosis: rapid antigen detection from swabs or washing of nasopharyngeal secretions. • Treatment: • Symptomatic treatment: acetaminophen and anti-tussives. • Specific treatment: oseltamivir and zanamivir. They must be given within 48 hours after the onset of symptoms to be effective. • Influenza vaccine: • It is recommended annually in general population. • It is contraindicated in patients with severe allergy to eggs because this can result in anaphylaxis. Pharyngitis and Influenza

13. Pharyngitis and Influenza

14. Bronchitis: • Definition: infection of the bronchial tree with LIMITED involvement of lung parenchyma. • Etiology: there are 2 types of bronchitis • Acute bronchitis: majority of cases are caused by viruses. Non-viral causes include: M.pneumoniae, C.pneumoniae and B.petussis. • Chronic bronchitis: S.pneumoniae, H.influenzae and Morexellacatarrhalis (similar to otitis media and sinusitis). Most common causative factor is smoking. • Diagnosis: suspect bronchitis in patient presenting with productive cough and clear lungs on examination and CXR. Patients might also have low-grade fever. • Treatment: • Acute bronchitis: most cases will resolve spontaneously because they are caused by viruses. • Acute exacerbations of chronic bronchitis: amoxicillin. If patient is not responding → amoxicillin/ clavulanic acid. • Lung abscess: • Definition: it is a collection of infected material within lung parenchyma. • Etiology: • 45% ONLY anaerobes, 45% anaerobes MIXED WITH aerobes and 10% ONLY aerobes. • Anaerobes: Peptostreptococcus, Prevotella and Fusobacterium species. • Aerobes: E.coli, Klebsiella. S,aureus and Pseudomonas. • Notice that 90% of patients have a clear association with gingival disease or some predisposition to aspiration. • Clinical manifestations: • Fever. • Productive cough with foul-smelling sputum. • Diagnosis: • CXR shows: thick-walled cavitary lesions. • CT-scan of the chest: to know the extent of the cavity. • To determine specific bacteria involved: aspiration of abscess fluid. • Treatment: clindamycin or penicillin (as empiric therapy). Bronchitis and Lung Abscess

15. Bronchitis and Lung Abscess CXR of lung abscess showing air-fluid level CT-scan of lung abscess

16. Definition: it is infection of the lung parenchyma. • Etiology: • Typical pneumonia (high-grade fever, cough and sputum production; consolidation): • S. pneumoniae: it is the most common cause of community-acquired pneumonia. • H.influenzae: causing pneumonia in smoker and those with COPD • Moraxellacatarrhalis. • Klebsiella: causing pneumonia in alcoholics. • Atypical pneumonia (low-grade fever with dry non-productive cough; interstitial infiltrates): • Mycoplasma pneumonia: it is seen in young healthy patients. It presents with dry cough. • Chlamydia pneumonia. • Legionella: from infected water-sources (such as air-conditioning systems). CNS manifestations (headache, confusion and lethargy) + GI manifestations (vomiting and diarrhea) might occur. • Viral causes are common in children > 5 years of age. • Pneumocystisjiroveci: causing pneumonia in HIV-positive patients with CD4 count > 200 cells/mm3. • Notes: • Most common causes of hospital-acquired pneumonia and ventilator-associated pneumonia are: • E.coli and other enterobacteriaceae. • Pseudomonas. • MRSA. • Clinical manifestations of typical pneumonia (bacterial pneumonia): • Usually high-grade fever. • Cough. • Sputum production: • Rust red sputum: suggesting infection with S.pneumoniae. • Currant-jelly sputum: suggesting infection with Klebsiella. • Dyspnea. • Pleuritic chest pain which is associated with consolidation and is increased with inspiration. • Physical examination of consolidation: • Palpation: increased tactile fremitus. • Percussion: dullness. • Auscultation: decreased air entry, bronchial breathing, rales and egophony (E changes to A). Pneumonia

17. Diagnosis: • The most important initial diagnostic test is CXR: • Typical pneumonia: lobar consolidation and usually parapneumonic pleural effusion. • Atypical pneumonia: bilateral interstitial infiltrates. • The most specific diagnostic test for LOBAR PNEUMONIA is sputum culture. • Atypical pneumonia organisms (Mycoplasma and Chlamydia) are detected by serology (antibody titers). • Empiric treatment: • Community-acquired pneumonia: • CURB-65 indicating the a patient with pneumonia must be hospitalized: • C: Confusion. • U: Uremia. • R: Respiratory distress (PO2 > 60 mmH, oxygen saturation > 95% and respiratory rate < 30 breaths/minute). • B: Blood pressure low (systolic > 90 mmHg or diastolic > 60 mmHg). • Age <65 years. These inpatients will be treated with ceftriaxone + azithromycin. • Outpatients are those who present with clinical manifestations corresponding to atypical pneumonia and will be treated with macrolides. Alternative are new fluoroquinolones (such as levofloxacin). • Hospital-acquired pneumonia (pneumoniae which develops in patients 5-7 days while staying in hospital): • Carbapenems (imipenem) or piperacillin/ tazobactam + vancomycin (to cover MRSA). • Vaccination: • Those who should receive a pneumococcal vaccine are immunocompromised patients, diabetics, smokers, alcoholics and patients < 65 years of age. Pneumonia

18. Pneumonia CXR of typical pneumonia showing consolidation CXR of atypical pneumonia caused by Mycoplasma

19. Definition/ etiology: • Tuberculosis (TB) is caused by: Mycobacterium tuberculosis. • Transmission: respiratory droplets. • BCG vaccination is 50% effective in preventing the disease but not indicated as a routine vaccination. • Those with high risk to get TB are: alcoholics, health workers, prisoners and those who are immunocompromised with increased risk for re-activation of a latent infection (HIV, leukemia, lymphoma, steroid use or organ transplantation). • Clinical manifestations: • Fever, night sweats, weight loss, cough, sputum production and sometimes hemoptysis. • Extrapulmonary TB: lymph node involvement (adenitis), Pott’s disease, meningitis and involvement of the bone marrow. • Diagnosis: • Best initial diagnostic test is CXR showing: apical involvement, infiltrates and cavitation. It might also show adenopathy or calcifications (Ghon complex). • Sputum sample for Acid-Fast Bacilli AFB (3 samples). • Sputum culture is more specific but not clinically practical because organism takes 4-6 weeks to grow. • The single most sensitive diagnostic test is pleural biopsy showing caseating ncerosis. • Treatment: • 2 months with (isoniazid, rifampin, ethambutol and pyrazinamide) + 4 months with (isoniazid and rifampin). • Side effects of drugs: • Isoniazid: peripheral neuropathy due to vitamin B6 deficiency (give supplements). • Rifampin: benign discoloration of body fluids (orange-red). • Ethambutol: optic neuritis. • Pyrazinamide: benign hyperuricemia (do not treat unless there are symptoms of gout). Tuberculosis

20. Tuberculosis

21. Tuberculosis CXR of a patient diagnosed with tuberculosis

22. PPD: it is a screening test used to screen asymptomatic population at increased risk for TB. A positive PPD test is determined by the measurment of skin induration 48-72 hours after intradermal injection of PPD: • ≥ 5 mm: • Close contacts to TB cases. • HIV-positive patients. • Those who use steroids or organ transplantation recipients. • ≥ 10 mm: • Healthcare workers. • Prisoners. • Immigrants from endemic areas. • Children > 4 years of age. • ≥ 15 mm: low-risk population (not mentioned above). • Positive PPD, abnormal CXR, 3 POSITIVE AFB smears → start TB therapy with the usual regimen. • Positive PPD, normal/abnormal CXR, 3 NEGATIVE AFB smears → isoniazid + vitamin B6 for 9 months. Tuberculosis

23. Food poisoning: presenting predominantly with vomiting. Incubation period is 1-6 hours. • Bacillus cereus: associated with re-heated Chinese fried rice at a moderate heat (containing spores). • S.aureus (contaminated meat). • Invasive organisms causing BLOODY infectious diarrhea are: • E.coli: it is the most common cause of traveler’s diarrhea. E.coli O157:H7 is associated with undercooked hamburger meat and it produces shiga-like toxin which results in hemolytic uremic syndrome. • Campylobacter jejuni: it is the most common cause of infectious diarrhea. It can result in reactive arthritis or Guillain-Barre syndrome (rarely). • Salmonella: it is associated with contaminated poultry and eggs. • Shigella. • Yersinia: it can mimic appendicitis. • Other causes of diarrhea: • Giardialamblia: from contaminated water sources. It produces large volume stool which is foul smellingbut with no blood. Notice that most common protozoan associated with blood in stool is Entamoebahistolytica. • Vibrio cholera: resulting in watery diarrhea. • Clostridium difficile: from use of antibiotics (commonly clindamycin). • Viruses: rotavirus and Norwalk virus are associated with outbreaks of diarrhea in children. • Clinical manifestations: • Diarrhea/vomiting and signs of dehydration. • Invasive organisms may also cause: bloody diarrhea, fever and abdominal pain. Notice that these are indications to use antibiotics (commonly fluoroquinolones) although the most important step in managing patients with diarrhea is fluid therapy. • Diagnosis: • Stool sample for fecal leukocytes. • Most specific: stool culture. • Also direct examination of stool for ova and parasites. Infectious Diarrhea and Food Poisoning

24. Definition: it is infection of the liver with hepatitis viruses: A, B, C, D and E. • Etiology: • Hepatitis A and E: • Transmission: feco-oral. • They do not cause chronic hepatitis. Therefore, there is no risk for liver cirrhosis or Hepatocellular Carcinoma (HCC). • Hepatitis E is more common in southeast Asia and can result in fulminant hepatitis in pregnant females. • Hepatitis A and E serology: IgM in active disease; IgG when they resolve. • There is a vaccine against hepatitis A. • Hepatitis B, C and D: • Transmission (parenteral): sexual contact, needlestick injury, blood products or perinatally. • Hepatitis D has to occur as a co-infection with hepatitis B. • Hepatitis B and C have chronic forms with increased risk for cirrhosis and HCC (especially with hepatitis C). • Remember that hepatitis C can be associated with cryoglobulinemia. • Remember that 30% of patients with PAN have active hepatitis B. • There is a vaccine against hepatitis B. • Clinical manifestations: fever, jaundice, dark urine, pale stool, fatigue/malaise, pain in the right hypochondrium and liver might be enlarged. • Diagnosis: • Liver Function Test (LFT): • All patients with viral or drug-induced hepatitis will have ↑direct bilirubin (jaundice with dark urine and pale stool). • Viral hepatitis: ↑ALT and AST (ALT < AST). • Alcohol or drug-induced hepatitis: ↑ALT ad AST (AST < ALT). • If there is severe damage to the liver: ↑PT and ↓albumin. Acute Viral Hepatic Infections

25. Acute Viral Hepatic Infections

26. Acute Viral Hepatic Infections

27. Diagnosis (continued): • How to differentiate between different types of hepatitis: • Hepatitis A: • Acute: presence of IgM antibody. • Resolved: presence of IgG antibody. • Hepatitis E: • Acute: presence of IgM antibody. • Resolved: presence of IgG antibody. • Hepatitis C: • Initial diagnosis of acute disease: anti-HCV (IgM). • Then, viral activity is followed-up with: PCR-RNA (for viral load). • Hepatitis B: • Treatment: • Chronic hepatitis B: interferon or lamivudine. • Hepatitis C: the newest drug combination is sofosbuvir/ledipasvir (Harvoni) which is effective against genotype 1 and the duration of treatment is 8-12 weeks. • After a needlestick injury from a patient with positive hepatitis B surface antigen → you must receive hepatitis B immunoglobulin and hepatitis B vaccine. • All newborn children are vaccinated against hepatitis A and hepatitis B. Acute Viral Hepatic Infections

28. Urethritis: • Definition: it is inflammation of the urethra. • Etiology: • Gonococcalurethritis: caused by Neisseria gonorrhea. • Non-gonococcalurethritis: caused by Chlamydia trachomatis or Ureaplasmaurealyticum. • Clinical presentation: purulent urethral discharge, dysuria, urgency and frequency. • Diagnosis: • Gonococcalurethritis: • Gram-staining: intracellular gram-negative diplococci. • Most specific diagnostic test is culture. • Non-gonococcalurethritis (Chlamydia): • Serology of urethral swabs. • Treatment: single-dose IM ceftriaxone + single-dose oral azithromycin. • Pelvic inflammatory disease (PID): • Definition: it is inflammation of ovaries, fallopian tubes, uterus and ligaments of the uterus. • Etiology: Neisseria gonorrhea or Chlamydia trachomatis. • Clinical presentation: • Most important (clue to diagnosis): lower abdominal and pelvic pain on palpation of the cervix, uterus or adnexa. • Fever, leukocytosis and discharge are also common. • Intrauterine devices predispose to PID. • Diagnosis: clinically but definitive diagnosis with laparoscopy. • Treatment: • Inpatient (high-grade fever or high EBCs): doxycycline and cefotetan (2nd generation cephalosporin). • Outpatient: single-dose IM ceftriaxone and oral doxycycline for 2 weeks. Genital and Sexually Transmitted Infections

29. Non-gonococcalurethritis discharge Genital and Sexually Transmitted Infections

30. Syphilis: • Definition/etiology: it is a systemic contagious disease which is caused by the spirochete Treponemapallidum (which cannot be stained with gram-staining). • Clinical manifestations: • Congenital: • Early: symptomatic; seen in infants up to 2 years of age. • Late: symptomatic; Hutchinson’s teeth, saber shin and scars of interstitial keratitis. • Acquired: • Primary: characterized by the presence of chancre (painless ulcer appearing 3 weeks after the infection and lasting for 10-90 days) and painless regional lymphadenopathy. Chancre occurs in following areas: • Males: penis, anus or rectum. • Females: vulva, cervix or perineum. • Secondary: characterized by skin rash (appearing 6-12 weeks after the infection), wart-like lesions on mucocutaneous junctions called condylomatalata (which are extremely infectious) and there might be alopecia. • Tertiary: mainly neurologic or cardiovascular (there is gumma formation). Tertiary syphilis occurs 3-20 years after the initial infection. • Diagnosis: • Screening tests: VSRL and RPR. False-positive results with: TB, EBV, subacuteendocarditis and collagen vascular disease. • Specific tests: FTA-ABS, MHA-TP and darkfiled examination of chancre (revealing the spirochetes). • Treatment: • Primary and secondary syphilis: 2.4 million units IM benzathine penicillin given once. • Tertiary syphilis: 10-20 million units IV penicillin for 10 days. Genital and Sexually Transmitted Infections

31. Electron micrograph of Treponemapallidum Genital and Sexually Transmitted Infections Primary syphilis (chancre) Secondary syphilis (rash) Tertiary syphilis (gumma)

32. Chancroid: • Definition: it is a localized contagious disease characterized by: • Painful genital ulcers (chancroid). • Suppuration of inguinal lymph nodes. • Etiology: • Hemophilusducreyi (gram-negative bacillus). • Clinical manifestations: • Small, smooth, painful genital papules which will become ulcers with ragged edges. • Swollen, painful inguinal lymph nodes. • Diagnosis: • Clinically. • Confirmed by: gram-staining and culture. • PCR is also useful. • Treatment: single-dose IM ceftriaxone. • Lymphgranulomavenereum: • Definition/etiology: it is a contagious sexually transmitted disease caused by Chlamydia trachomatis. • Clinical manifestations: • Fever, headache, malaise and joint pain. • Small, transient lesion which ulcerates and heals quickly. • Painful unilateral enlargement of inguinal lymph nodes leaving a scar later. • Diagnosis: clinical. • Treatment : doxycycline. Genital and Sexually Transmitted Infections

33. Granulomainguinale (Donovaniagranulomatis): • Etiology: Calymmatobacteriumgranulomatis. • Clinical manifestations: • Painless red nodules developing into elevated granulomatous mass. • Males: penis, scrotum, groin and thighs. • Females: vulva, vagina and perineum. • Healing is slow and there is scar formation. • Diagnosis: • Clinically. • Can be confirmed by the presence of Donovan bodies with Wright/Giemsa stain (punch biopsy). • Treatment: doxycycline. • Genital herpes: • Etiology: Herpes Simplex Virus (HSV) type-1. • Clinical manifestations: mucocutaneous vesicles which can rupture and be converted to painful ulcers which leave a scar. There might be swollen inguinal lymph nodes. • Diagnosis: • Clinical. • Can be confirmed with: Tzank smear and viral culture. • Treatment: oral acyclovir. Acyclovir-resistant cases → foscarent. • Genital warts (condylomataacuminata): • Etiology: Human Papilloma Virus (HPV). • Clinical manifestations: small, soft, pink/red swelling which grow and become pedunculated (cauliflower-appearance). • Diagnosis: clinically but you have to differentiate it from condylomata lata of secondary syphilis. • Treatment: cryotherapy, curettage or laser removal. Genital and Sexually Transmitted Infections

34. Cystitis: • Definition: infection/inflammation of the urinary bladder. • Epidemiology: more common in females. • Etiology: • Foreign bodies (such as catheters). • Stasis of urine caused by stones, tumors, neurogenic bladder or prostatic hyperplasia. • Sexual intercourse in females (honeymoon cystitis caused by Staphylococcus saprophyticus). • Most common organism involved is E.coli (<80% of cases). Others are: Klebsiella, Proteus and Enterococcus. • Clinical manifestations: • Suprapubic pain (most common). • Urinary symptoms: dysuria, urgency and frequency. • Diagnosis: • Urinalysis: ↑WBCs and nitrites. • Urine culture: < 100,000 colonies of bacteria/ml or urine. • Treatment: • Uncomplicated cystitis: 3 days of trimethoprim/sulfamethoxazole or any of the quinolones. • Notice that quinolones are contraindicated in pregnancy. • Duration of treatment in diabetics: 7 days. Urinary Tract Infections

35. Acute pyelonephritis: • Definition: it is a unilateral, pyogenic infection (producing pus) of the kidney. • Epidemiology: more common in females during childhood, pregnancy and after catheterization. • Etiology: • Ascending infection due to the following predisposing factors: stones, tumors, neurogenic bladder, prostatic hyperplasia or vesicureteral reflux. • Most common organism is E.coli followed by Kleblsiella, Proteus and Enterococcus. • Clinical manifestations: • Fever/chills, flank pain, constovertebral angle tenderness and urinary symptoms (dysuria, urgency and frequency). • Diagnosis: • Urinalysis: ↑WBCs, leukocyte esterase and nitrites. • Urine culture: < 100,000 colonies/ ml of urine. • Treatment: • 10-14 days antibiotics with: fluoroquinolones or ceftriaxone. • Perinephric abscess: • Definition: collection of infected material around the kidney. • Etiology: • Stones are the most important and present in 20-60% of cases. • Pathogenesis: stone → pyelonephritis → renal abscess → rupturing through the cortex into perinephric space. • Pathogens: E.coli (most common) followed by Klebsiella and Proteus. • Clinical manifestations: • Gradual with fever and flank/abdominal pain and palpable abdominal mass. • Diagnosis: • Pyuria with negative urine culture. • Imaging: ultrasound, but CT/MRI are more accurate. • Definitive diagnosis: aspiration of the abscess. • Treatment: • Percutaneous drainage and antibiotics (3rd generation cephalosporin + aminoglycoside). Urinary Tract Infections

36. Urinary Tract Infections Histopathology of acute pyelonephritis CT-scan showing acute pyelonephritis Acute pyelonephritis morphology

37. Osteomyelitis: • Definition: infection involving any part of the bone: medulla, cortex or periosteum. • Etiology: there are 3 types of osteomyelitis • Acute hematogenous: more common in children; occurring in metaphysis of long bones of lower extremities (femur and tibia); single organism involved in 95% of cases (most commonly S.aureus). • Secondary to contiguous infection: occurring in those with recent trauma to an area or placement of a prosthetic joint; a single organism is involved in most cases (commonly S.aureus). • Vascular insufficiency: occurring in those with diabetes or peripheral vascular disease with age < 50 years; usually polymicrobial (but S.aureus is still the most common cause). • Clinical manifestations: • Area over the bone will be painful, erythematous and swollen. Ulceration is present when patient has vascular insufficiency. In addition, a draining sinus tract is present. • Diagnosis: • Initial → x-ray: periosteal elevation (but this takes nearly 2 weeks to occur). • To detect early osteomyelitis: technetium bone scan and MRI. • Most accurate but most invasive: bone biopsy and culture. • Treatment: • Acute hematogenousosteomyelitis in children: antibiotics only (anti-staphylococcal). • Osteomyelitis in adults: surgical debridement + empiric antibiotics (anti-staphylococcal penicillins/ vancomycin if MRSA is suspected + ceftriaxone). Empiric therapy is then changed when results of culture and sensitivity are obtained. Bone and joint infections

38. Acute osteomyelitis MRI Bone and joint infections

39. Septic arthritis: • Definition: infection of a joint. • Etiology: septic arthritis is divided to • Gonococcal arthritis: the single most common risk factor being sexual activity. • Non-gonococcal arthritis: caused by S.aureus or Streptococci and transmitted by hematogenous route. Other ways of transmission include: bite (human/animals), surgery or trauma. • Clinical presentation: • Gonococcal arthritis: polyarticular, skin manifestations are common, tenosynovitis is common, migratory polyarthralgia is common, effusions are less common. • Non-gonococcal: monoarticular, commonly affecting the knee with signs of inflammation, skin manifestations are rare. • Diagnosis: • Gonococcal: culture is negative in 50% of cases. Therefore, you rely on cell count of synovial aspirate (< 50,000 WBCs). • Non-gonococcal: culture is positive in most of cases, synovial fluid has < 50,000 cells predominantly neutrophils with low glucose. • Treatment: • Gonococcal: ceftriaxone. • Non-gonococcal: anti-staphylococcal antibiotics or vancomycin when MRSA is suspected + ceftriaxone. Bone and joint infections

40. Gas gangrene: • Definition: necrotizing destruction of muscles caused by gas-producing organisms + signs of sepsis. • Etiology: most of cases are associated with traumatic injury which will result in infection of the wound with Clostridium prefringens. The wound must be deep enough and has no exit to the surface. • Clinical manifestations: • Appearing within 1-4 days after infection of the wound. • Early: pain and swelling (edema). • Later: hypotension, tachycardia, fever and crepitations over site of infection with renal failure. • Diagnosis: • Gram-staining and culture for Clostridium: gram-positive rods with WBCs. • X-ray: gas bubbles. • Most accurate: surgical debridement. • Treatment: • High-dose penicillin (24 million units/day). • Mainstay of treatment: surgical debridement or amputation. Bone and joint infections

41. Definition: it is colonization of heart valves (commonly aortic and mitral valves) by microbial organisms resulting in: • Fever. • Vegetations. • Valve destruction. • Predisposing factors for infective endocarditis: • Previous history of infective endocarditis. • Prosthetic heart valve. • Dental procedures which cause bleeding. • Oral or upper respiratory tract surgeries. • Genitourinary surgeries. • IV drug abuse. • Etiology: most common 3 bacterial organisms causing infective endocarditis are • Staphylococcus aureus. • Staphylococcus epidermidis. • Streptococcus viridans. • Classifications: there are 2 types of infective endocarditis • Acute infective endocarditis: commonly caused by S.aureus; seeding previously normal valves; resulting in fever, large vegetations (2mm – 2cm) and rapid valve destruction; also associated with splenomegaly and embolic complications (especially to the lungs with right-sided lesions); IV drug abuse is a major risk factor. • Subacute infective endocarditis: commonly caused by Streptococcus viridans; seeding previously abnormal valves; resulting in low-grade fever, small vegetations and slow destruction of valves; risk factors include: prosthetic valves, mitral prolapse, bicuspid aortic valve or stenosis of any valve; mortality is less than acute infective endocarditis. Infective Endocarditis

42. Clinical manifestations: most important being • Fever (90%) • New heart murmur of changing murmur (90%) • Embolic events (50%). • Skin manifestations (50%): • Petechiae (20-30%): red, non-blanching lesions found on conjunctiva, buccal mucosa, palate or extremities. • Splinter hemorrhage (15%): linear, red-brown streaks on the nails. • Janeway lesions (10-15%): red, painless macules on palms or soles. • Osler’s nodes: painful nodules on pads of fingers or toes. • Roth’s spots: oval, pale retinal lesions surrounded by hemorrhage. • Complications of infective endocarditis: • CHF (most common cause of death). • Septic embolization. • Glomerulonephritis with nephrotic syndrome or renal failure. • Diagnosis: modified Duke’s criteria (you need the two major criteria OR 1 major + 2 minors criteria): Infective Endocarditis

43. Treatment: • You will start empiric treatment but you will change it as soon as you get the results of blood cultures and sensitivity tests. • Empiric therapy: • S.aureus (treatment duration: 4-6 weeks): • Methicillin-sensitive: naficillin + 5 days of gentamicin. If patients is allergic to penicillin: vancomycin + 5 days of gentamicin. • Methicillin-resistant: vancomycin. • Strep. viridans: • Penicllin. If patient is allergic to penicillin: ceftriaxone of vancomycin. • Prevention of bacterial endocarditis: • Prophylaxis with antibiotics is needed in dental procedures resulting in bleeding especially with the following anatomic defects: • Prosthetic heart valves. • Transplant status. • Unrepaired cyanotic heart disease. • Previous history of bacterial endocarditis. Amoxicillin is given; penicillin-allergic patients will receive macrolides (azithromycin). Infective Endocarditis

44. Definition/Etiology: AIDS is caused by Human Immunodeficiency Virus (HIV). HIV is transmitted through unprotected sex, IV drug abuse, blood products and from pregnant mother to her baby. • Pathogenesis: HIV affects CD4 helper T-cells. A drop in CD4 count and rise in viral load over time predispose the patient for Opportunistic Infections (OI) and some malignancies. There is a 10-year lag between infection with HIV and appearance of first symptoms. • Opportunistic Infections (OI): • Pneumocystic jirovecii (CD4 count > 200 cells/ µL): • Clinical manifestations (pneumonia): fever, dry cough, dyspnea and chest pain. • Diagnosis: • CXR: bilateral interstitial infiltrates. • Bronchoalveolar lavage for direct identification of the organism. • ↑serum LDH. • Treatment: trimethoprim-sulfamethoxazole (TMP-SMZ). • Prophylaxis: TMP-SMZ which can be discontinued if antiretroviral therapy increases CD4 count < 200 cells/µL for < 6 months. • Cytomegalovirus (CD4 count > 50 cells/µL): • Clinical manifestations: • Retinitis: blurry vision, double vision or any other visual disturbances. • Colitis: diarrhea (>20% of patients). • Esophagitis: fever, odynophagia and retrosternal chest pain. • Encephalitis: altered mental status. • Diagnosis: • Fundoscopy for retinitis. • Colonoscopy and biopsy for diarrhea or upper GI endoscopy and biopsy for esophagitis. • Treatment: • Oral valganciclovir. • Those who cannot tolerate oral therapy or have CNS manifestations → IV ganciclovir. Acquired Immune Deficiency Syndrome (AIDS)

45. Opportunistic Infections OI (continued): • Mycobacterium Avium Complex MAC (CD4 count > 50 cells/µL): • Transmission: inhalation or ingestion. • Clinical manifestations: fever, night sweats, anemia, wasting, diarrhea and bacteremia. • Diagnosis: • Blood culture. • Culture of bone marrow, liver or other body tissues/fluids. • Treatment: clarithromycin and ethambutol (±rifabutin). • Prophylaxis: oral azithromycin once a week which can be discontinued of antiretroviral therapy increases CD4 cell count < 100 cells/ µL for several months. • Toxoplasmosis (CD4 count > 100 cells/µL): • Clinical manifestations (brain mass): headache, confusion, seizures and focal neurologic deficits. • Diagnosis: head CT/MRI showing (ring) contrast enhancing lesion with edema and mass effect. • Treatment: pyrimethamine and sulfadiazine. • Prophylaxis: TMP/SMZ. • Cryptococcosis (CD4 count > 100 cells/µL): • Clinical manifestations (meningitis): fever, headache and malaise. • Diagnosis: • Lumbar puncture with india ink analysis of CSF. • CSF cryptococcus antigen testing. • Serum cryptococcus antigen testing. • Treatment: amphotericin for 10-14 days (+ flucytosine) followed by oral fluconazole as maintenance and suppressive therapy. • Vaccinations: all HIV-positive patients must receive vaccinations for influenza, pneumococcus and hepatitis B Acquired Immune Deficiency Syndrome (AIDS)

46. CD4 cell count: • It is the most accurate method for determining what infections or other diseases the patient is at risk for: • < 700 cells/µL: normal • > 500 cells/µL: oral thrush and Kaposi sarcoma. • > 200 cells/µL: Pneumocystisjirovecii • > 100 cells/µL: Toxoplasmosis and Cryptococcosis. • > 50 cells/µL: CMV and MAC. • Viral load: • The best test to monitor response to antiretroviral therapy is HIV-RNA viral load. • A high viral load generally indicates that the level of CD4 cells is going to drop more rapidly. • The goal is complete suppression if viremia> 50-70 copies of HIV-RNA/mL. • Antiretroviral therapy: • Regimen: start antiretroviral therapy once you diagnose a patient with HIV (regardless of CD4 cell count): • 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) + Protease Inhibitor (PI). • OR 2 NRTIs + 1 Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI). • Antiretroviral therapy is considered to be ADEQUATE: when there is drop of ≥ 50% of viral load within the first month after initiating antiretroviral therapy. • Pregnant patients: • Without treatment, 25-30% of children born to HIV-positive mothers will be truly HIV positive. • Pregnant females discovered to be HIV-positive must receive treatment in the same regimen as for those non-pregnant patients. Notice that efavirenz (NNRTI) is the only antiretroviral medication which is contraindicated in pregnany. • C-section is only done when there is failure to control the disease with antiretroviral therapy (e.g. high viral load < 1000 copies of HIV-RNA/mL at time of delivery). • Breast-feeding is associated with transmission of the virus to the infant. Acquired Immune Deficiency Syndrome (AIDS)

47. Tetanus: • Definition/etiology: it is an infectious complication of a wound caused caused by Clostridium tetani which produces a neurotoxin. Clostridium tetani is a gram-positive rod producing spores. Tetanus occurs 1-7 days after infection of the wound. • Clinical manifestations: • Tonic spasm of voluntary muscles resulting in stiff neck, arms and legs. There will be flexion of arms and extension of lower extremities with lockjaw. • Dysphagia. • Respiratory arrest. • Diagnosis: clinical. • Treatment: • Penicillin 10-14 days. • Surgical debridement of the wound. • Tetanus immunoglobulin. • Prophylaxis: tetanus toxoid (Tdap) boosters every 10 years. • Aspergillosis: • Definition/etiology: it is a fungal infection mainly affecting the lung and caused by Aspergillusfumigatus. • Clinical presentation: • Allergic bronchopulmonary-like asthma with: fever, cough and wheezing. • If there is a mycetoma (fungal ball):hemoptysis would be a chief complaint. • Notice that 90% of patients have 2 of these 3 risk factors: neutropenia> 500, steroid use or the use of cytotoxic drugs (azathioprine or cyclophosphamide). • Diagnosis: • ↑eosinophils and IgE level. • Abnormal CXR. • Presence of Aspergillus in sputum. • Treatment: • Allergic: steroids and asthma drugs. • Mycetoma: surgical removal. • Invasive disease: voriconazole. Tetanus and Aspergillosis Aspergillus Mycetoma