superinfection

2. SUPERINFECTIONS

3. SUPERINFECTION
• Appearance of new infection as a result of antimicrobial therapy
• Normally, pathogen competes with normal bacterial flora.
• Antimicrobial drug suppresses part of normal flora, susceptible to
drug.
• Drug resistant organism proliferates to an extent which allows an
infection to be established.

4. PREDISPOSING CONDITIONS
• Corticosteroid therapy.
• Leukemia
• AIDS
• Diabetes, SLE
• Use of broad spectrum antibiotics tetracyclines, chloramphenicol,
ampicillins, newer cephalosporins.

5. ORGANISMS INVOLVED
• Candida albicans
• Clostridium difficile
• HCV
• HIV
• Aspergillus spp.
• Resistant staphylococci

6. Candida albicans
• Small, thin-walled, ovoid yeast
• Measures 4–6 μm in diameter
• Reproduce by budding.
• Blastospores, pseudohyphae, and hyphae.
• Identified by biochemical testing or on special agar

8. MUCOCUTANEOUS CANDIDIASIS
• Superficial fungal infection.
• Predisposing factors:
• Diabetes, Obesity
• Pregnancy
• Systemic antibiotics, chemotherapy, oral corticosteroids
• Wearing denture
• Poor Oral hygiene.

9. CLINICAL FEATURES
• Severe pruritus of vulva, anus/body folds.
• Superficial, denuded, beefy-red areas with/without satellite vesicopustules.
• Oral candidiasis:
• Fluctuating throat/mouth discomfort
• Erythema of oral cavity
• Fluffy, white patches on oropharynx.

12. DIAGNOSIS
• Visualization of pseudo hyphae or hyphae; in presence of
inflammation:
• on wet mount (saline and 10% KOH),
• tissue Gram’s stain,
• periodic acid–Schiff stain,
• methenamine silver stain

13. TREATMENT
• Fluconazole (100 mg orally daily for 7 days)
• Ketoconazole (200–400 mg orally with breakfast for 7–14 days)
• Clotrimazole troches (10 mg dissolved orally five times daily)
• Nystatin mouth rinses (500,000 units [5 mL of 100,000 units/mL] three
times daily)
• For HIV infection, longer courses of therapy with fluconazole may be
needed, and oral Itraconazole (200 mg/d) may be indicated in fluconazole-
refractory cases.

14. VULVOVAGINAL CANDIDIASIS- TREATMENT
1. Single- dose regimens:
• Miconazole (200-mg vaginal suppository),
• Tioconazole (6.5% cream, 5 g vaginally),
• Sustained-release Butoconazole (2% cream, 5 g vaginally),
• Fluconazole (150 mg oral tablet).

15. VULVOVAGINAL CANDIDIASIS- TREATMENT
2. Three- day regimens:
• Butoconazole (2% cream, 5 g vaginally once daily),
• Clotrimazole (2% cream, 5 g vaginally once daily),
• Terconazole (0.8% cream, 5 g, or 80 mg vaginal suppository once daily),
• Miconazole (200 mg vaginal suppository once daily).

16. VULVOVAGINAL CANDIDIASIS- TREATMENT
3. Seven- day regimens:
• Clotrimazole (1% cream)
• Miconazole (2% cream, 5 g, or 100 mg vaginal suppository) once daily
• Terconazole (0.4% cream, 5 g).

17. VULVOVAGINAL CANDIDIASIS- TREATMENT
4. Fourteen- day regimen:
Nystatin (100,000-unit vaginal tablet once daily).
5. Recurrent vulvovaginal candidiasis (maintenance therapy):
• Clotrimazole (500 mg vaginal suppository once weekly or 200 mg cream
twice weekly)
• Fluconazole (100, 150, or 200 mg orally once weekly)

18. Clostridium difficile INFECTION
• Obligate anaerobic, gram-positive, spore-forming bacillus
• Major cause of diarrhea in patients hospitalized for more than 3 days
• Affecting 22 patients of every 1000.
• Acquired by feco-oral transmission

19. RISK FACTORS
• Elderly; debilitated;
• Immunocompromised;
• Receiving multiple antibiotics or prolonged (> 10 days) antibiotic therapy;
• Receiving enteral tube feedings,
• Inflammatory bowel disease

20. DRUGS CAUSING CDI
• Cephalosporins: cefotaxime, ceftriaxone, cefuroxime, and ceftazidime
• Fluroquinolones: ciprofloxacin, levofloxacin, and moxifloxacin
• Proton Pump Inhibitors
• SSRI’s
• Cholinesterase Inhibitors
• Metformin

21. Postgrad Med J 2005;81:367–369

22. CLINICAL FEATURES
• Greenish foul smelling watery diarrhea- 5-15 times/day
• Lower abdominal cramps
• Tenderness- left lower quadrant
• Fever, hemodynamic instability, abdominal distention

23. Harrison’s Principles of Internal Medicine- 19th edition

25. PNEUMONIA

26. Davidson’s Principles and Practice of Medicine, 21st edition.

27. TREATMENT
• When there is low risk for multiple drug–resistant pathogens, use one of the
following:
• Ceftriaxone, 1–2 g intravenously every 12–24 hours
• Gemifloxacin, 320 mg orally daily
• Moxifloxacin, 400 mg orally or intravenously daily
• Levofloxacin, 750 mg orally or intravenously daily
• Ciprofloxacin, 400 mg intravenously every 8–12 hours
• Ampicillin-sulbactam, 1.5–3 g intravenously every 6 hours
• Piperacillin-tazobactam 3.375–4.5 g intravenously every 6 hours
• Ertapenem, 1 g intravenously daily
CMDT 2015 Page: 273

28. • When there is higher risk for multiple drug-resistant pathogens, use one
agent from each of the following categories:
1. Antipseudomonal coverage:
• Cefipime, 1–2 g intravenously twice a day or ceftazidime, 1–2 g
intravenously every 8 hours
• Imipenem, 0.5–1 g intravenously every 6–8 hours or meropenem, 1 g
intravenously every 8 hours
• Piperacillin-tazobactam, 3.375–4.5 g intravenously every 6 hours
• For penicillin-allergic patients, aztreonam, 1–2 g intravenously every 6–12
hours
CMDT 2015 Page: 273

29. 2. A second antipseudomonal agent
• Levofloxacin, 750 mg intravenously daily or ciprofloxacin, 400 mg
intravenously every 8–12 hours
• Intravenous gentamicin, tobramycin, amikacin, all weight-based dosing
administered daily adjusted to appropriate trough levels
3. Coverage for MRSA if appropriate with either
• Intravenous vancomycin (interval dosing based on renal function to
achieve serum trough concentration 15–20 mcg/mL)
• Linezolid, 600 mg intravenously twice a day

30. BRONCHOPULMONARY ASPERGILLOSIS
• Caused by Aspergillus fumigatus
• A hypersensitivity reaction to germinating fungal spores.
• Complicates asthma (1-2%) and cystic fibrosis (5-10%)

32. BRONCHOPULMONARY ASPERGILLOSIS-
FACTORS
• SYSTEMIC FACTORS:
• Metabolic disorders: diabetes mellitus
• Chronic alcoholism
• HIV and AIDS
• Corticosteroids and other immunosuppressant medication
• Radiotherapy
• LOCAL FACTORS:
• Tissue damage by suppuration or necrosis
• Alteration of normal bacterial flora by antibiotic therapy

33. BRONCHOPULMONARY ASPERGILLOSIS-
FEATURES
• Asthma (in the majority of cases)
• Proximal bronchiectasis (inner two-thirds of chest CT field)
• Elevated total serum IgE > 417 KU/L or 1000 ng/mL
• Peripheral blood eosinophilia > 0.5 × 109/L
• Presence or history of chest X-ray abnormalities
• Fungal hyphae of A. fumigatus on microscopic examination of sputum

34. BRONCHOPULMONARY ASPERGILLOSIS-
MANAGEMENT
• Low-dose oral corticosteroids prednisolone 7.5–10 mg daily
• Itraconazole 400 mg/day 4-months
• Use of specific anti-IgE monoclonal antibodies is under consideration

35. HCV
COINFECTION/SUPERINFECTION/REINFECTION
• Co-infection is defined as infection with ≥2 heterologous HCVs
simultaneously or within a very narrow window period before
infection with the first HCV has resulted in an immunologic response
to that virus.
Blackard, 2007. J Inf Dis 195:519

36. HCV
COINFECTION/SUPERINFECTION/REINFECTION
• Superinfection is defined as infection with a second HCV after the
establishment of persistent HCV infection and development of an
immunologic response to the first virus.
Blackard, 2007. J Inf Dis 195:519

37. HCV
COINFECTION/SUPERINFECTION/REINFECTION
• Reinfection describes a primary infection that is completely cleared
virologically prior to a subsequent, secondary infection with either a
homologous or a heterologous HCV.
Blackard, 2007. J Inf Dis 195:519

38. CONSEQUENCES OF HCV SUPERINFECTION
• Reduced efficacy of HCV treatment.
• Limited immunologic cross-protection which may reduce the efficacy of
future HCV vaccines.
• Elevated levels of transaminase and/or hepatitis flares.
• Alterations in levels of HCV RNA.
• Development of recombinant viruses with enhanced pathogenic
potential.

39. TREATMENT
• Treatment of choice pegylated α-interferon given weekly
subcutaneously
• Combined with Oral Ribavirin, a synthetic nucleotide analogue.
• Side effects of interferon flu-like symptoms, irritability and depression
• Side effects of ribavirin hemolytic anaemia
• Protease Inhibitors (Telaprevir & Bocevavir) under clinical trial

40. HIV & HCV CO-INFECTION
• Determinants:
• >80% hemophiliacs
• 70-80% injection drug users
• 3-5% heterosexuals
• Higher in females
• Higher CD4 counts
• Raised transaminases.

42. TREATMENT
• Combined Rx of peginterferon and ribavirin has been shown to be
efficacious.
• HIV treatment initiated to optimise the CD4 count ≥ 350cells/mm3.
• If HAART co-administered, nucleotide reverse transcriptase inhibitors
like ZDV, didanosine & abacavir avoided.

43. HEPATITIS D
• A defective RNA virus;
• Causes hepatitis only in association with HBV infection.
• Coinfect/superinfect HBV

44. SEVERITY
• Co-infection similar to acute hepatitis B.
• Superinfection carries worst short term prognosis.
• Results in severe chronic hepatitis cirrhosis increased risk of
hepatocellular carcinoma.
• Rx effective management of hepatitis B

45. REFERENCES
• Essentials of Medical Pharmacology, K. D. Tripathi, 6th edition
• Current Medical Diagnosis and Treatment 2015
• Davidson’s Principles and Practice of Medicine, 21st edition.
• Harrison’s Principles of Internal Medicine- 19th edition

46. REFERENCES
• Blackard, 2007. J Inf Dis 195:519
• I Tonna, P D Welsby, Pathogenesis and treatment of Clostridium
difficile infection, Postgrad Med J 2005;81:367–369
• Kelesidis T, Pothoulakis C, Efficacy and safety of the
probiotic Saccharomyces boulardii for the prevention and therapy of
gastrointestinal disorders, Therap Adv Gastroenterol. 2012
March; 5(2): 111–125.

47. THANK YOU