Superinfection

superinfection

1. SUPERINFECTIONS

2. 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.

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

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

5. Candida albicans Small , thin-walled, ovoid yeast Measures 4–6 μm in diameter Reproduce by budding . B lastospores , pseudohyphae, and hyphae . I dentified by biochemical testing or on special agar

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

7. 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.

8. DIAGNOSIS V isualization 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

9. TREATMENT F luconazole (100 mg orally daily for 7 days ) K etoconazole (200–400 mg orally with breakfast for 7–14 days ) C lotrimazole troches (10 mg dissolved orally five times daily) N ystatin 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 I traconazole (200 mg/d) may be indicated in fluconazole- refractory cases.

10. VULVOVAGINAL CANDIDIASIS- TREATMENT Single- dose regimens: M iconazole (200-mg vaginal suppository ), Tioconazole (6.5 % cream, 5 g vaginally ), Sustained-release B utoconazole (2% cream, 5 g vaginally ), Fluconazole (150 mg oral tablet ).

11. 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).

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

13. 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)

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

15. RISK FACTORS Elderly ; debilitated; I mmunocompromised ; R eceiving multiple antibiotics or prolonged (> 10 days ) antibiotic therapy ; R eceiving enteral tube feedings, Inflammatory bowel disease

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

17. Postgrad Med J 2005;81:367–369

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

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

20. PNEUMONIA

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

22. 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

23. When there is higher risk for multiple drug-resistant pathogens, use one agent from each of the following categories: 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

24. 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

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

26. 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

27. 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

28. BRONCHOPULMONARY ASPERGILLOSIS- MANAGEMENT L ow-dose oral corticosteroids  prednisolone 7.5–10 mg daily Itraconazole 400 mg/day  4-months U se of specific anti- IgE monoclonal antibodies is under consideration

29. 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

30. 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

31. 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

32. CONSEQUENCES OF HCV SUPERINFECTION Reduced efficacy of HCV treatment. L imited immunologic cross-protection which may reduce the efficacy of future HCV vaccines. Elevated levels of transaminase and/or hepatitis flares. A lterations in levels of HCV RNA . D evelopment of recombinant viruses with enhanced pathogenic potential.

33. 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 ( T elaprevir & Bocevavir ) under clinical trial

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

35. TREATMENT Combined R x of peginterferon and ribavirin has been shown to be efficacious. HIV treatment  initiated  to optimise the CD4 count ≥ 350cells/mm 3 . If HAART co-administered, nucleotide reverse transcriptase inhibitors like ZDV , didanosine & abacavir  avoided.

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

37. 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. R x  effective management of hepatitis B

38. REFERENCES Essentials of Medical Pharmacology, K. D. T ripathi , 6 th edition Current Medical Diagnosis and Treatment 2015 Davidson’s Principles and Practice of Medicine, 21 st edition . Harrison’s Principles of Internal Medicine- 19 th edition

39. 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.

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