Superinfections occur when a new infection develops due to antimicrobial therapy weakening the normal microbiota. This allows overgrowth of resistant organisms. Predisposing conditions include corticosteroid use, immunosuppression, and broad-spectrum antibiotics. Common superinfecting organisms are Candida, Clostridium difficile, HCV, HIV, and Aspergillus. Candida commonly causes oral and vulvovaginal infections treatable with antifungals. C. difficile causes diarrhea treatable with vancomycin or fidaxomicin. Aspergillus may complicate lung disease and is managed with antifungals and steroids.

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