Essentials of diagnosis Suspected anaerobic infetons: foul odor of draining purulence presence of gas in tissues no organism growth on aerobic culture media infection localized in the proximity of mucosal surface presence of septic thrombophlebitis tissue necrosis and abscess formation association with malignancies (especially intestinal)
Tetanus the source of infection is the soil (spores) toxin production (tetanospasmin) binds to ganglioside receptors stops nerve impulse to muscles spastic paralysis severe muscle contractions and spasms can be fatal
C. botulinum Foodborne botulism Incubation period: hrs. Symptoms: ptosis, double vision, inability to swallow, speech difficulty, bulbar paralysis, constipation, and abdominal pain. Bilateral descending weakness of peripheral muscle. Death occurs from respiratory paralysis (mostly) or cardiac arrest. No fever. Mortality is reduced through better supportive care. Recovery may need months to years. Patients who recover do not develop antitoxin.
Treatment respiration polivalent anti-toxin (iv., in every 4 hours) antibiotics (penicillin, clindamycin)
C. perfringens 1. gas gangrene, myositis (lecithinase) - oedema - gas production 2. food poisoning (enterotoxin) - vomiting - no fever
Diagnosis clinical culture
Treatment antibiotics surgical debridement local hidrogen-peroxide solution into the wound amputation There is a fulminant type, the patient could die within 2 days.
Clostridium difficile infections (CDI) 3 million cases of diarrhea and colitis annually in the United States mortality rate is % CDI and CDI related deaths is a significant and growing problem in hospitals and care homes early diagnosis and prompt aggressive treatment are critical AAD % AAC % >90% - pseudomembranous colitis
Named „difficult clostridium” due to its resistance in isolation and growth
Clinical Manifestations Asymptomatic carriage (neonates) Diarrhoea –5-10 days after starting antibiotics maybe be 1 day after starting may be up to 10 weeks after stopping may be after single dose –spectrum of disease: brief, self limiting cholera-like - 20X/day, watery stool
Pathogenesis Disruption of normal colonic flora Colonisation with C. difficile Production of toxin A +/- B or binary toxin Mucosal injury and inflammation
PCR Ribotype 027 North American outbreak strain: –8 to 16 X production of toxins A and B in-vitro Hyper-toxin production: –18bp deletion in the TcdC gene –regulates toxin production Strong association with fluoroquinolone use The Lancet 24 th Sept 2005: –Warny, Pepin, Fang, Killgore, Thompson, Brazier, Frost and McDonald: “Toxin production by an emerging strain of C. difficile associated with outbreaks of severe disease in North America and Europe”
Risk factors Admission to intensive care unit Advanced age Antibiotic therapy Immunosuppressive therapy Multiple and severe underlying diseases Placement of a nasogastric tube Prolonged hospital stay Recent surgical procedure Residing in a nursing home Sharing a hospital room with a C. difficile infected patient Use of antacids
Diagnosis demonstration of toxin antigens from the feces (immunchromatography) culture colonoscopy AXR
Treatment algorithm for new cases of C. difficile diarrhoea Symptomatic proven or suspected C. difficile infection Assess patient: AXR, CRP, WBC Stool for C. difficile toxin production and culture Review antibiotics
Moderate Disease Well WBC < 20 CRP <150 Normal AXR Severe Disease Unwell WC > 20 * CRP >150 * Abnormal AXR * Distended Abdomen * (* = severe if any of these features)
( If deteriorates to severe ) Start treatment without delay -Vancomycin 4x500mg per os (!) -Metronidazole 2x500mg iv. or 2x 400mg per os -IVIG -Daily surgical review until improving : if fails to improve consider surgery Start treatment without delay -Metronidazole 2x400mg for 5 days -Daily review WBC, CRP, AXR Moderate Severe
Response Complete 14 day course of Vancomycin Complete course of metronidazole No Response :- Refer gastroenterology for flexible sigmoidoscopy & advice New drug: fidaxomicin (Dificlir ® ) Response Complete 14 day course of metronidazole No Response :- Add Vancomycin 4x 500mg per os for 5 days Complete 14 day course of metronidazole
Treatment problems 25 % of cases are relapsing within 30 days selection of vancomycin resistant strains such as VRE
DIFICLIR ® (fidaxomicin) bactericidal macrocylic antibiotic blocks the bacterial enzyme RNA polymerase 2x200 mg (2x1 tablet) for 10 days
Dificlir ® (fidaxomicin) Inhibition of the clostridial RNA polymerase occurs at a concentration 20- fold lower than that of the E. coli enzyme; this partially explains the specificity of fidaxomicin activity. In addition, fidaxomicin is not significantly systemically absorbed and is considered to be a topically acting drug. It is associated with minimal disruption of normal gut flora.
Comments for treatment Motility inhibitors, such as Lomotil® or Imodium® are PROHIBITED! vancomycin suspension available for neonates
Hand washing health care workers should practice good hand hygiene before and after treating each person in their care using soap and warm water is a better choice for hand hygiene, as alcohol-based hand sanitizers may not effectively destroy C. difficile spores visitors also should be diligent about washing hands with soap and warm water before and after leaving the room or using the bathroom
Contact precautions isolation of the patient if possible hospital staff and visitors wear disposable gloves and gowns while in the room in any setting, all surfaces should be carefully disinfected with a product that contains chlorine bleach. C. difficile spores can survive routine cleaning products that don't contain bleach
Predisposing factors trauma of tissues tissue ischemia systemic diseases (diabetes) presence of foreign devices (IUD) manipulation of bowel (postsurgical abdominal infections) administration of broad-spectrum antibiotics (antibiotic-associated pseudomembranous colitis)
Lung abscess A lung abscess is a localized pus cavity in the lung May be a complication of pneumonia or of large- volume aspiration Often associated with periodontal disease Single abscesses are most common Anaerobes are prevalent, but aerobes are often involved as well Treatment: antibiotics (often with surgical drainage). Clindamycin is a good choice (not metronidazole). Penicillin G might be effective.
Lung (aspiration) abscess
Brain abscess Organisms gain access to the brain hematogenously, directly from a contiguous infected site, or after trauma or surgery. The mouth is a common source. Most common symptom: headache Usual organisms: streptococci plus anaerobes Diagnosis made by CT or MRI Treatment: surgical drainage plus prolonged antibiotics ( metronidazole + ceftriaxone)
Brain abscess CT
Intra-abdominal infection Primary (spontaneous bacterial peritonitis, SBP) or secondary Organisms –SBP: monomicrobial (enteric Gram-negative rods) –Secondary: polymicrobial (enteric Gram- negative + anaerobes) Hospital-acquired infection has a high mortality rate Treatment –SBP: antibiotics plus longterm prophylaxis –Secondary: surgical repair plus antibiotics
Actinomycosis chronic infection most frequently on the neck other localisations: thoracic, abdominal, brain actinomycosis mainly in male alcoholism is a co-factor after trauma, oral surgery pus is yellow (sulfur granules)
Treatment long, 1- 2 month penicillin iv., 6-12 month penicillin per os surgical
Pelvic inflammatory disease (PID) Infection of the female reproductive organs Can involve the Fallopian tubes, cervix, uterus, and ovaries Peak incidence: late teens, early 20s Presentation is nonspecific Organisms: Neisseria gonorrhoeae,, Chlamydia, enteric Gram-negatives, anaerobes Complications: sterility, ectopic pregnancy Treatment: aggressive antimicrobial therapy (oral OK if infection is mild)
Diabetic foot infection A serious complication of diabetes that may lead to amputation (not all diabetic foot ulcers are infected) Poor circulation results in thin and vulnerable skin; diabetes-associated neuropathy may impair sensation and therefore awareness of foot trauma Symptoms include redness, swelling, and pain Bacteriology: mixed aerobic/anaerobic organisms, difficult to identify Treatment: surgical debridement plus broad- spectrum antibiotics (not necessarily with curative intent)
Decubitus Decubitus ulcer is a sore obtained as a result of pressure which is commonly known as bed sore. The wound may sometimes extend to the bone and to internal organs through bones. Pressure is one of the main causes for decubitus ulcer. Some areas prone to this ulcer are hips, spine, elbows, heels.
Drug of choice in anaerobic infections Empirical therapy: Gram-negative: metronidazole (Klion ®, Flagyl ®) Gram-positive: clindamycin (Dalacin C ®) Other anti-anaerobical drugs: imipenem (Tienam ®), meropenem (Meronem®) piperacillin+tazobactam (Tazocin ®), amoxicillin+clavulanic acid (Augmentin ®), ampicillin+sulbactam (Unasyn®) moxifloxacin (Avelox ®) tigecycline (Tigacyl ®)
Treatment of infections caused by anaerobes GroupFirst choiceAlternativesComments anaerobic Gram- negative rods metronidazole 500 mg iv. every 6 h clindamycin 900 mg iv. every 8 h Fusobacterium sensitive to penicillin anaerobic Gram- negative cocci penicillin G million U iv. clindamycin 900 mg iv. every 8 h metronidazole not recommended anaerobic Gram- positive nonspore- forming rods penicillin G million U iv. clindamycin 900 mg iv. every 8 h widespread resistance to metronidazole anaerobic Gram- positive spore- forming rods penicillin G million U iv. metronidazole 500 mg iv. every 6 h anaerobic Gram- positive cocci penicillin G million U iv. clindamycin 900 mg iv. every 8 h antibiotic- associated colitis metronidazole 250 mg p.o. 3x (7-14 days) vancomycin 125 mg per os 4x (7- 10 days) stop other antibiotics
Dosage of other anti-anaerobic drugs imipenem: 500 mg iv. every 6 h meropenem: 1 g iv. every 8 h piperacillin/tazobactam: g iv. every 6 h ampicillin/sulbactam: g iv. every 6 h amoxicillin/clavulanic acid: 500 mg orally every 8 h
Pediatric dosing penicillin U/kg/d metronidazole 30 mg/kg/d clindamycin 25 mg/kg/d (in patients with normal renal and hepatic functions)