ANAEROBIC INFECTIONS

Judit SzabóMD. PhD.

Endogenous and exogenous sources

• endogenous:

Source: normal flora

• exogenous • Source: soil (spores) eg.clostridia,

toxic )

Anaerobic infections

• abscess formation• chronic otitis, sinusitis, mastoiditis• aspiration pneumonia• peritonitis, appendicitis• diabetic foot, ulcer, decubitus• PID (actinomycosis)• C. difficile infection

Pathogenesis

• supressed neutrophil killing • enzymes (collagenase, hyaluronidase)• capsule (B. fragilis) antiphagocytic• toxins (Clostridia)• sinergism between aerobic and

anaerobic bacteria)

Co-factors

• tissue degradation • tissue ischemia• systemic diseases (eg. diabetes)• IUD• damages of mucosal membranes

(surgery)• wide spectrum antibiotics (killing of

bowel flora, pseudomembranous colitis)

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)

Infections associated with anaerobic bacteria

Localisation Clinical symptoms

head-neck chronic sinusitis, otitis, mastoiditisodontogenic , periodontal diseasesperitonsillar abscess

central nerve system brain abscess, epidural abscesssubdural empyema

respiratory tract aspiration pneumonia, empyema

intra-abdominal peritonitis, intra-abdominal abscess, appendicitis, liver abscess, enteritis necrotizans, postoperative wound infections, neutropenic enterocolitis

female genital tract endometritis, amnionitis, septic abortion, PID

skin-soft-tissue bite wounds, diabetic foot, decubitus, necrotizing fasciitis, cellulitis, gas gangrene

toxin-mediated (clostridial) disease

botulism, tetanus, antibiotic associated pseudomembranous colitis

Clostridial infections

1. Neurotoxic clostridia-C. tetani-C. botulinum

2. Histotoxic clostridia-C. perfringens-C. difficile

Tetanus

the source of infection is the soil (spores)

toxin production (tetanospasmin)binds to ganglioside receptors stops nerve impulse to muscles spastic paralysissevere muscle contractions and spasms can be fatal

Opisthotonus

Diagnosis

Clinical (diff. dg.: strychnin poisoning)

• microscopic investigation

• culture

Treatment

• antitoxin

• hiperbaric oxigen

• antibiotics (penicillin, clindamycin)

• respiratory support

• benzodiazepins

• alfa and beta adrenerg blocking drugs

C. botulinum

• food poisoning (preformed toxin)

eg.canned food

• infant newborn botulism (eg.honey)

• wound botulism (rare)

C. botulinum

Foodborne botulism

Incubation period: 18-24 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.

Diagnosis

Diff. dg.: myasthenia gravis, Lambert-Eaton paraneoplastic syndrome, Guillan-Barre syndrome

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

Gas gangrene

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 1 - 2.5 %• 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 -20-30%• AAC - 50-75%• >90% - pseudomembranous colitis

Named „difficult clostridium” due to its resistance in isolation and growth

Clinical ManifestationsClinical 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

Clinical ManifestationsClinical Manifestations

• Additional symptoms:– abdominal pain, fever, nausea, malaise, anorexia,

hypoalbuminaemia, colonic bleeding, dehydration• Acute toxic megacolon

– acute dilatation of colon– systemic toxicity– signs of obstruction– high mortality (64%)

• Colonic perforation

PathogenesisPathogenesis

• Disruption of normal colonic flora• Colonisation with C. difficile• Production of toxin A +/- B or binary

toxin• Mucosal injury and inflammation

PCR Ribotype 027PCR 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 24th 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

C. difficileC. difficile – Antibiotic – Antibiotic RiskRisk

High Risk Antibiotics:

CefotaximeCeftriaxoneCefalexinCefuroximeCeftazidimeCiprofloxacinMoxifloxacinClindamycin (low dose)

Medium Risk Antibiotics:

MeropenemErtapenemClindamycin (high dose)Co-amoxiclavTazocinErythromycinClarithromycin

C. difficileC. difficile – Antibiotic – Antibiotic RiskRisk

Low Risk Antibiotics:

Benzyl penicillin GentamicinAmoxicillin MetronidazoleFlucloxacillin VancomycinTetracyclines TeicoplaninTrimethoprim SynercidNitrofurantoin Linezolid Fusidic acid TigecyclineRifampicin Daptomycin

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, WBCStool for C. difficile toxin production and culture Review antibiotics

Moderate DiseaseWellWBC < 20CRP <150Normal AXR

Severe Disease Unwell WC > 20 *CRP >150 *Abnormal AXR *Distended Abdomen *(* = severe if any of these features)

( If deterioratesto 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

ResponseComplete 14 day course of Vancomycin Complete course of metronidazole

No Response :-Refer gastroenterology for flexible sigmoidoscopy & adviceNew drug: fidaxomicin (Dificlir ®)

ResponseComplete 14 day course of metronidazole

No Response :-Add Vancomycin 4x 500mg per os for 5 daysComplete 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

Prognosis

Prevention

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

Infections caused by non spore forming anaerobic

bacteria

abscess formation

chronic otitis, sinusitis, mastoiditis

diabetic foot, ulcer, decubitus

peritonitis, appendicitis

aspiration pneumonia

PID

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)

Actinomycosis on the face

Thoracic actinomycosis

Diagnosis

• histological: "sulfur granulues„ • Gram stain: Gram-positive rods (”filaments”)• Culture (long, 7-10 days)

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)

Diabetic foot

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 .

Decubitus

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

Group First choice Alternatives Comments

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 10-24 million U iv.

clindamycin 900 mg iv. every 8 h

metronidazole not recommended

anaerobic Gram-positive nonspore-forming rods

penicillin G 10-24 million U iv.

clindamycin 900 mg iv. every 8 h

widespread resistance to metronidazole

anaerobic Gram-positive spore-forming rods

penicillin G 10-24 million U iv.

metronidazole 500 mg iv. every 6 h

anaerobic Gram-positive cocci

penicillin G 10-24 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: 3.375 g iv.

every 6 h• ampicillin/sulbactam: 1.5-3.0 g iv.

every 6 h• amoxicillin/clavulanic acid: 500 mg

orally every 8 h

Pediatric dosing

• penicillin 25 000 U/kg/d• metronidazole 30 mg/kg/d• clindamycin 25 mg/kg/d

(in patients with normal renal and hepatic functions)