Guidelines C.Diff (June 2017)

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This optimal usage guide is intended for health professionals. It is provided for information purposes only and does not replace the clinician’s judgement. The recommendations were developed using a systematic approach and are supported by the scientific literature and the knowledge and experience of Québec clinicians and experts. For further details, go to inesss.qc.ca.

DRUG ANTIBIOTICS

JUNE 2017

GENERAL

Clostridium difficile (C. difficile) is a bacterium that initiates a sporulation process when conditions are unfavou- rable for its survival. C. difficile-associated diarrhea is caused by toxigenic strains.

Its sporulated form, which is highly resistant to dryness and various biological and chemical agents, enables it to spread and persist.

In favourable conditions, the spore germinates, assumes a vegetative form and multiplies, producing toxins that cause inflammation of the colonic mucosa and severe diarrhea.

In certain individuals, C. difficile is part of the intestinal microbial flora but without causing any clinical symptoms, as evidenced by the prevalence of asymptomatic carriers.

Prevalence rates in asymptomatic carriers by age group : •15 to 63 % in newborns

•3 to 33 % in infants and children under 2 years of age •8 % of children aged 2 years and older

•2 to 5 % of healthy adults •10 to 20 % of the elderly

PEDIATRIC CONSIDERATIONS

Diarrhea is a common adverse effect associated with antibiotic use. Therefore, most cases of post-antibiotic diarrhea in children are not caused by C. difficile.

There has been a slight increase in pediatric C. difficile infections in recent years.

In children, the most common clinical manifestation of C. difficile infection is profuse diarrhea.

Diagnostic tests should not be ordered in children less than 1 year of age.

PREVENTIVE MEASURES

In hospitals :

•Place the patient in isolation and apply the hospital’s infection prevention measures.

•Wash your hands with soap and water, vigorously rubbing them to eliminate any spores. Remind the patient of the importance of handwashing.

! Alcohol-based gels are ineffective against C. difficile spores.

•Disinfect the patient’s surroundings.

! Unlike alcohol, sodium hypochlorite (e.g., bleach) is effective in destroying the spores.

TREATMENT OF CLOSTRIDIUM DIFFICILE- ASSOCIATED DIARRHEA OR COLITIS

TREATMENT OF CLOSTRIDIUM DIFFICILE- ASSOCIATED DIARRHEA OR COLITIS

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PROBIOTICS

Although there is a low level of scientific evidence that certain probiotic formulations may confer benefits in terms of preventing C. difficile-associated diarrhea (CDAD), no favourable recommendation can be made with the current state of knowledge because of the significant methodological limitations of the clinical trials. For further information, consult the report entitled : Usage des probiotiques en prévention des diarrhées associées à Clostridium difficile chez les patients hospitalisés sous antibiothérapie, au Québec.

RISK FACTORS

When a patient has diarrhea, check if he/she has taken any antibiotics in the past 2 months, as they increase the risk of contracting C. difficile infection, especially if the patient has taken any of the following antibiotics (in the order of risk) :

•Clindamycin;

•A cephalosporin, especially a 2^nd or 3^rd generation one;

•A fluoroquinolone.

The risk is higher in patients who, in addition : •Have a history of such an infection;

•Are taking a proton pump inhibitor (PPI);

•Have been hospitalized in the past 2 months;

•Have an inflammatory bowel disease;

•Are elderly, especially if they live in a long-term care setting;

•Are immunocompromised.

DIAGNOSIS

If a patient has important diarrhea, check if he/she has used any antibiotics in the past 2 months, especially those listed above.

Confirm the clinical diagnosis with a toxin screen (a bacterial stool culture is not the appropriate test).

! Check that the diarrhea is well established (3 liquid stools in more or less 24 hours) before obtaining a sample for a diagnostic test.

Determine the severity of the infection using the table below.

A test of cure after treatment is not recommended.

Do not perform tests in asymptomatic patients.

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INFECTION SEVERITY

¹

Mild

Adult A mild infection is any infection that does not meet the criteria for a severe infection.

Child Watery diarrhea with no systemic toxicity; 3 or 4 abnormal stools per day.

Severe

Adult

Look for the following severity criteria :

•A white blood cell count ≥ 15 x 10⁹ cells/l

•A 50 % or greater increase in the serum creatinine level above the person’s usual baseline level

•Documented temperature > 38.5 °C

•Albumin < 30 g/l

Child Signs of systemic toxicity (e.g., high fever or chills)

Complicated Adult

Look for signs of complication :

•Hypotension, whether or not vasopressors are required, or septic shock

•^Ileus² or toxic megacolon

•Bowel perforation

•^Septicemia

•Changes in mental status

•White blood cell count ≥ 35 x 10⁹ cells/l or < 2 x 10⁹ cells/l

•Serum lactate > 2.2 mmol/l

•Any evidence of organ failure

Child Signs of systemic toxicity or severe colitis, including hypotension, septic shock, ileus, peritonitis or megacolon

Recurrence Reappearance of the symptoms of C. difficile infection occurring after symptom resolution within 8 weeks of the previous infection.

1 The clinical signs listed below are based on expert opinion, since the infection severity criteria have not been validated.

2 The signs and symptoms of ileus include acute nausea, vomiting, the sudden cessation of diarrhea, abdominal distention and radiological signs consistent with ileus (distension, fluid-air levels).

TREATMENT PRINCIPLES

GENERAL MEASURES

Discontinue all treatments involving :

•Antiperistaltic agents, such as loperamide or diphenoxylate;

•^Laxatives.

Reevaluate and discontinue, if possible : •Antibiotics;

•^PPIs;

•Opioids (because of the risk of bowel perforation).

Do not treat asymptomatic carriers.

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ANTIBIOTIC THERAPY IN ADULTS

It is reasonable to initiate empirical treatment in certain situations while awaiting the diagnosis. Discontinue the empirical treatment if the toxin screen turns out to be negative.

Mild infection

Metronidazole 500 mg PO TID x

10 days

!

Vancomycin**

125 mg PO QID x 10 days if pregnancy

or if breastfeeding

or if intolerance, allergy or contra-

indication to metronidazole

or if patient is at

high risk for complications*

if deterioration or no response to treatment with

metronidazole after 3 to 5 days

Vancomycin*

125 mg PO QID x 14 days

if deterioration

and Vancomycin*

125 to 500 mg PO QID AND metronidazole

500 mg IV TID

Refer patient to a specialist

Refer patient to a specialist Refer patient

to a specialist Severe

infection Complicated

infection If patient cannot be treated orally

1

^ST

EPISODE

Repeat initial treatment

42-day treatment, as follows :

Vancomycin* : 125 mg PO QID x 7 days 125 mg PO BID x 7 days 125 mg PO OD x 7 days 125 mg every 2 days x 7 days 125 mg every 3 days x 14 days

If additional recurrence, refer patient to a specialist

1^st recurrence > 1 recurrence

RECURRENCE

* Example : age > 65 years, comorbidity, admission to intensive care unit, and immunocompromised state

** If allergy to vancomycin : fidaxomicin 200 mg PO BID x 10 days (exception drug)

! Drug interactions with metronidazole and warfarin

If the patient is taking an antibiotic for another indication, it is not advisable to administer antibiotics against C. difficile as prophylaxis. However, in certain specific situations, for example, for treating patients with a his- tory of multiple recurrences of C. difficile infection, it may be acceptable to do so. If applicable, treatment with 125 mg of vancomycin PO QID would be indicated, this up to one week after the patient stops taking the antibiotic for the first indication.

Most patients respond to a first treatment, and 20 to 25 % of patients will

experience a recurrence TREATMENT OF CLOSTRIDIUM DIFFICILE- ASSOCIATED DIARRHEA OR COLITIS

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ANTIBIOTIC THERAPY IN CHILDREN

If the child cannot be treated orally, refer him/her to a specialist.

* In the event of a complete ileus, consider adding rectal instillation of vancomycin (maximum : 2 g/day).

Repeat initial treatment

Vancomycin* : 40 mg/kg/day divided into 4 doses x 7 days (max. : 125 mg QID) 20 mg/kg/day divided into 2 doses x 7 days (max. : 125 mg BID) 10 mg/kg/day as 1 dose x 7 days (max. : 125 mg daily)

10 mg/kg/day as 1 dose every 2 days x 7 days (max. : 125 mg every 2 days) 10 mg/kg/day as 1 dose every 3 days x 14 days (max. : 125 mg every 3 days)

If additional recurrence, refer patient to a specialist

1^st recurrence > 1 recurrence

RECURRENCE

Mild infection

Mild infection that does not

respond to withdrawal of the causative antibiotic Discontinue

causative

antibiotic Metronidazole 30 mg/kg/day PO divided into 3 or 4

doses x 10 to 14 days (maximum

1.5 g/day)

Vancomycin 40 mg/kg/day divided into 4 oral

doses x 10 to 14 days (maximum

125 mg PO QID) if intolerance,

allergy or contraindication to metronidazole Follow-up and

reevaluation

Follow-up and reevaluation

and

and Vancomycin 40 mg/kg/day

divided into 4 doses or by

nasogastric tube, plus IV metronidazole

30 mg/kg/day divided into 4 doses x 10 to 14 days* (maximum :

500 mg QID) Vancomycin

40 mg/kg/day PO divided into 4 doses x 10 to 14 days (maximum : 125 mg PO QID)

Refer patient to a specialist

Refer patient to a specialist Severe

infection Complicated

infection

1

^ER

ÉPISODE

if deterioration or no response to treatment with

metronidazole after 3 to 5 days.

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MAIN REFERENCES

Allen UD and Canadian Paediatric Society Infectious Diseases and Immunization Committee. Clostridium difficile in paediatric populations. Paediatr Child Health 2014;19(1):43-8.

Cohen SH et al. Clinical practice guidelines for Clostridium difficile infection in adults : 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infection Control and Hospital Epidemiology, 2010, 31(5) : 431-455.

Dubberke ER et al. Strategies to prevent Clostridium difficile infections in acute care hospitals : 2014 Update, Infection control and hospital epidemiology. 2014, 35(6):

628-645.

Fitzpatrick F. Surveillance, diagnosis and management of Clostridium difficile infection in Ireland - National Clinical Guideline No. 3. National Clinical Effectiveness Commit- tee (NCEC), June 2014. 151 pages.

Trubiano JA et al. Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand. Royal Australasian College of Physicians. 2016 : 479-493.

Agence de la santé publique du Canada. Clostridium difficile - Fiche technique santé - sécurité : agents pathogens. Sept. 2014, 3 pages.

CADTH. Proton Pump Inhibitors and C. Difficile : A Review of the Clinical Evidence. Sept. 2014, 30 pages.

It should be noted that other references were consulted.