Ontario Antimicrobial Stewardship Project Evidence-Based Summaries for Short-Course

Ontario Antimicrobial
Stewardship Project
Evidence-Based Summaries
for Short-Course
Antimicrobial Therapy
Draft 2009
Institute for Safe Medication Practices Canada
4711 Yonge Street, Suite 501, Toronto, ON M2N 6K8 • 416-733-3131 • 1-866-544-7672
Ontario Antimicrobial Stewardship Project
Evidence-Based Summaries for Short-Course Antimicrobial Therapy
With the increasing incidence of Clostridium difficile- Infection, and the continued emergence of multidrug resistant organisms, the appropriate use of antibiotics is a priority issue for healthcare providers
and patients. As part of the Ontario Antimicrobial Stewardship Project a series of 1-2 page evidencebased summaries for short-course antimicrobial therapy has been developed for selected infection
syndromes in order to assist healthcare facilities and practitioners in optimizing antimicrobial therapy.
The following documents are drafts of the first series of these documents which we are including for
your information and consideration as a possible intervention for antimicrobial stewardship.
These documents will undergo external expert review prior to circulation. Your comments or
suggestions are also welcome. Please forward any comments to Dr. Linda Dresser at
[email protected]
Ontario Antimicrobial Stewardship Project
Evidence-Based Summary for Short-Course Antimicrobial Therapy:
Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
1. In patients who require antibiotics for mild to moderate AECOPD, the duration of therapy should
be limited to a short-course of treatment of 5 days.
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is defined as a sustained
worsening of dyspnea, cough or sputum production leading to an increase in the use of
maintenance medications and/or supplementation with additional medications.1 Antibiotic therapy
has been shown to be effective and is indicated in AECOPD when at least 2 out of the 3 following
signs are present: increased dyspnea, increased sputum volume, increased sputum purulence
(Type 1 and 2 exacerbations).1,2 Recent evidence suggests that short-courses of antibiotic therapy
(≤ 5 days) are as effective as conventional longer treatment in patients with acute exacerbations
of chronic bronchitis and COPD, without respiratory failure, the majority of whom were treated as
outpatients .3,4
El Moussaoui and colleagues conducted a meta-analysis of 21 randomized clinical trials with a
total of 10,698 subjects, most of whom were outpatients.3 The mean duration of treatment was 4.9
days in the short treatment groups and 8.3 days in the long treatment groups. The summary Odds
Ratio (OR) for early clinical cure was 0.99 (95% CI 0.90-1.08) indicating no difference between
short-course versus conventional treatment duration. Similarly, when grouped by antibiotic class
the observed OR also indicated no difference in early clinical cure for short-term antibiotic use
compared to long-term use: cephalosporins OR 1.04 (95% CI 0.87-1.04), macrolides OR 0.96
(95% CI 0.80-1.16), fluoroquinolones OR 0.94 (95% CI 0.81-1.09). Further, trials with the same
antibiotic in both arms showed no difference in outcomes between short-course and conventional
duration of therapy (OR 0.93, 95% CI 0.78-1.11). The clinical cure rates as well as bacteriological
cure rates at both early and late follow-up were comparable for both treatment strategies.
A second meta-analysis of 7 randomized trials (3083 outpatients) examining short- versus longduration of antibiotics for AECOPD was conducted comparing regimens of the same antibiotic in
both treatment arms.4 Short-duration of antibiotic therapy lasted 5 days while long-duration
treatment lasted 7 or 10 days. No difference in treatment success was observed between patients
with AECOPD receiving the same antimicrobial for short versus long periods in both the Intentionto-Treat (RR 0.99, 95% CI 0.95-1.03) or clinically evaluable (RR 0.99 95% CI 0.96-1.02) groups.
Patients who received short- compared to long-duration antimicrobial therapy experienced fewer
adverse events (RR 0.84, 95% CI 0.72-0.97). There was no difference between the compared
groups regarding the eradication of H. influenzae (RR 1.00 95% CI 0.91-1.09), M. catarrhalis (RR
0.94, 95% CI 0.83-1.06) and S. pneumoniae (RR 1.01, 95% CI 0.86-1.19).
On the basis of the pooled results presented in each of these meta-analyses, short-course
treatment with antibiotics (5 days) is equally efficacious as longer courses (7-10 days), both in
terms of achieving clinical cure and eradication of bacteria from sputum. The results are the same
in trials in which short and longer courses of the same antibiotic were included and when
antibiotics were grouped by class. Shorter treatment durations confer the added benefit of fewer
side effects, better patient compliance and reduced risk of antibiotic resistance development.
Short-course antibiotic therapy can be used in those patients with mild to moderate exacerbations,
i.e. those patients not in respiratory failure requiring hospitalization.
Short Course Therapy for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
References
1. O’Donnell DE, Hernandez P, Kaplan A, et al. Canadian Thoracic Society recommendations for
the management of chronic obstructive pulmonary disease – 2008 update – highlights for
primary care. Can Respir J. 2008;15(Suppl A):1A-8A
2. Anthonisen NR, Marfreda J, Warren CPW, et al. Antibiotic therapy in exacerbations of chronic
obstructive pulmonary disease. Ann Intern Med 1987;106:196-204
3. El Moussaoui R, Roede BM, Speelman P, et al. Short-course antibiotic treatment in acute
exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies.
Thorax 2008;63:415-22
4. Falagas ME, Avgeri SG, Mathaiou DK, et al. Short-versus long-duration antimicrobial
treatment for exacerbations of chronic bronchitis: a meta-analysis. J Antimicrob Chemother
2008;62:442-50
Acknowledgements:
ISMP Canada gratefully acknowledges the input provided by Rene Breault BScPhm, Pharm D
(student) and the expert review by (to be determined). Page 2 of 2
Ontario Antimicrobial Stewardship Project
Evidence-Based Summary for Short-Course Antimicrobial Therapy:
Community-Acquired Pneumonia
1. A minimum treatment duration of 5 days of appropriate antibiotic therapy is recommended for
treatment of patients with mild-moderate community acquired pneumonia (CAP), provided
patients meet the criteria set out in the IDSA guidelines for clinical stability. For patients admitted
to a medical unit (not ICU) with CAP treatment duration of 5-7 days is appropriate provided the
patient is afebrile for 48h and meets criteria for clinical stability.
The 2007 IDSA Consensus Guidelines for the management of CAP in adults recommend that
treatment should continue for a minimum of 5 days, with the conditions that the patient be afebrile
for 48-72 hours and should have no more than 1 parameter that does not meet the CAPassociated criteria for clinical stability(4). These criteria include a temperature of ≤37.8°C, a heart
rate of ≤100 beats per minute, a respiratory rate of ≤24 breaths per minute, a systolic blood
pressure of ≥90mmHg, arterial O2 saturation of ≥90% or pO2 ≥60mmHg on room air, able to
maintain oral intake and normal mental status.
A meta-analysis compared the clinical efficacy of a short-course (7 days or less) antibiotic
monotherapy regimen versus an extended course (>7 days) regimen (4). Among the 15
randomized controlled trials included which had enrolled patients with radiographically confirmed
pneumonia, short-course regimens compared contained primarily azithromycin, and also betalactams, fluoroquinolones, and ketolides(4). Overall there was no difference in the risk of clinical
failure between the short and extended-course regimens. Additionally there were no differences
in the risk of mortality. A key consideration in the application of this data was that the majority of
included studies excluded patients with severe disease.
There is evidence supporting shorter treatment duration than 7 days for several individual classes
of antibiotics.
Amoxicillin
A randomized, double blind study in the Netherlands of 121 adults with mild to moderate CAP
treated for 3 days with amoxicillin compared continuation with 5 days of active therapy versus
placebo in initial responders. Clinical success rate, defined as resolution or improvement of
symptoms and clinical signs related to pneumonia without the need for additional or alternative
antibiotic therapy, was similar in both groups at days 10 and 28. Radiographic resolution, a
secondary endpoint, was also found to be similar between groups. The group excluded from initial
randomization due to lack of clinical improvement at 3 days was found to have higher rates of P.
aeruginosa, E. coli, and S. aureus positive cultures. If a shorter course is selected, close
monitoring is recommended within the first 3 days for response and appropriateness of antibiotic
should be evaluated based on culture results. (5)
Levofloxacin
Due to its concentration-dependent bactericidal activity, using the higher dose of 750mg of
levofloxicin maximizes its activity, enabling a shorter treatment duration.(6) A multicenter,
randomized, double-blind study compared levofloxacin 750mg per day for 5 days with 500mg per
day for 10 days in 528 patients with mild to moderate CAP. (6) Clinical cure was similar between
groups, among patients that were clinically evaluable (~92% in both groups), at the 7-14 day post
therapy visit. There was no difference in rates of adverse events between groups.
Short Course Therapy for Community Acquired Pneumonia
A similar randomized controlled trial was performed using gemifloxacin, comparing 5 and 7 day
courses of therapy in 469 outpatients with mild-moderate CAP. Results also demonstrated the
shorter course (5 days) to be non-inferior with respect to clinical cure and radiological success. (7)
Azithromycin
The efficacy of azithromycin short-course therapy has also been examined. A randomized, multicentre study compared azithromycin 500mg once daily for 3 days to clarithromycin 250mg twice
daily for 10 days in 203 outpatients with mild-moderate CAP. (8) No difference between groups
was found with respect to clinical cure or bacteriological response at the end of therapy (between
days 12-16). It should be noted that due to the long half life of azithromycin (~70 hours); a 3 day
course of therapy has a similar duration of exposure as a longer course of other alternatives.
Based on a review of available literature, it is recommended that if patients with mild-moderate
CAP are clinically stable (as defined by IDSA guidelines (4)), they should be treated for a
minimum of 5 days of appropriate antibiotic therapy. This shortened duration of exposure to
antibiotics may decrease the risk of CDAD.
References
1. Valiquette L, Cossette B, Garant M, et al. Impact of a Reduction in the Use of High-Risk
Antibiotics on the Course of an Epidemic of Clostridium difficile-Associated Disease Caused
by the Hypervirulent NAP1/027 Strain. CID. 2007;45:S112-121.
2. Bignardi GE. Risk factors for Clostridium difficile infection. J Hosp Infect. 1998;40:1-15
3. Pepin J, Saheb N, Coulombe MA et al. Emergence of Fluoroquinolones as the predominant
risk factor for Clostridium difficile-Associdated Diarrhea: a Cohort Study during an Epidemic in
Quebec. CID. 2005;41(9):1254-60.
4. Mandell L, Wunderink R, Anueto A, et al. IDSA/ATS Guidelines on the Management of
Community-Acquired Pneumonia in Adults. CID. 2007;44:S27-72.
5. Li J, Winston L, Moore D et al. Efficacy of Short-Course Antibiotic Regimens for Community –
Acquired Pneumonia: A meta-analysis. The American Journal of Medicine. 2007;120:783-790.
6. el Moussaoul R, de Borgie C, van den Broek P, et al. Effectiveness of discontinuing antibiotic
treatment after three days versus eight days in mild to moderate-severe community acquired
pneumonia: randomised, double blind study. BMJ 2006;332:1355-42.
7. Dunbar L, Wunderink R, Habib M, et al. High-Dose, Short-Course Levofloxacin for
Community-Acquired Pneumonia: A New Treatment Paradigm. CID 2003;37:752-761.
8. File T, Mandell L, Tillotson G, et al. Gemifloxacin once daily for 5 days versus 7 days for the
treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study.
Journal of Antimicrobial Chemotherapy. 2007;60:112-120.
9. O’Doherty B, Muller O, et al. Randomized, Multicentre Study of the Efficacy and Tolerance of
Azithromycin versus Clarithromycin in the Treatment of Adults with Mild to Moderate
Community-Acquired Pneumonia. Eur J Clin Microbiol Infect Dis. 1998;17:828-833.
10. D’Ignazio J, Camere M, Lewis D, et al. Novel, Single-Dose Microsphere Formulation of
Azithromycin versus 7-Day Levofloxacin Therapy for Treatment of Mild to Moderate
Community–Acquired Pneumonia in Adults. Antimicrobial Agents and Chemotherapy.
2005;49(10):4035-4041.
11. Scalera N, File T. How long should we treat community-acquired pneumonia? Curr Opin
Infect Dis. 2007;20:177-181.
Acknowledgements:
ISMP Canada gratefully acknowledges the input provided by Laura Murphy, Pharm D and the expert
review by (to be determined).
Page 2 of 2
Ontario Antimicrobial Stewardship Project
Evidence-Based Summary for Short-Course Antimicrobial Therapy:
Ventilator-associated Pneumonia (VAP)
1. Treatment with a total of 8 days of adequate antimicrobial therapy for proven VAP is appropriate.
Because of higher rates of relapse with infections due to P. aeruginosa or mdr- Acinetobacter spp.
consider extending duration to 15 days.
A randomized controlled trial in 197 patients with VAP compared 8 days versus 15 days of
antibiotic treatment. (2) Patients were included if they were intubated with mechanical ventilation
for >48 hours, had positive cultures (distal pulmonary secretion samples, BAL or protected
specimens), a diagnosis of VAP (new infiltrate on chest radiograph and either purulent tracheal
secretions, a temperature of >38.3°C or a leukocyte count >10000/uL), and were started on
appropriate empirical antibiotic therapy.(2) Exclusion criteria were pregnancy, a SAPS II score
>65 points, neutropenia, AIDS, had received stage 3 immunosuppression or long term steroids,
concomitant extra pulmonary infection, bacteremia or shock.(2) Empirical antibiotic selection was
left to the discretion of the treating physician, but the preferred regimen was initially an
aminoglycoside or fluoroquinolone plus a broad spectrum beta-lactam, then targeted therapy after
48-72 hours. Overall at day 28 of follow-up, 8 days of therapy was found to be non-inferior to 15
days of therapy for all cause mortality and microbiologically documented infection recurrence
rate.(2) Secondary endpoints also demonstrated no significant differences in 60 day mortality,
length of stay in the ICU or hospital, or number of days ventilated.(2) For primary infections
caused by non fermenting gram-negative bacilli i.e. Pseudomonas aeruginosa or Acinetobacter
spp., a higher percentage of patients in the group treated with 8 days developed pulmonary
infection recurrence. It would therefore be prudent to continue therapy for a total duration of 15
days in patients when these are isolated.
2. Patients with suspected VAP should be reassessed at 96h and their antibiotics discontinued if
CPIS score is <6. Other early discontinuation strategies for patients with suspected VAP may be
effective.
Evidence-based clinical practice guidelines for ventilator-associated pneumonia(1), developed by
the Canadian Critical Care Trials Group recommend the use of an antibiotic discontinuation
strategy based on clinical criteria, concluding that this shortens the duration of antibiotic therapy
with no adverse effects on clinical outcome.
An antibiotic discontinuation strategy such as the clinical pulmonary infection score (CPIS) was
demonstrated to shorten the duration of antibiotics.(3) The clinical CPIS includes criteria of
temperature, blood leukocytes, tracheal secretions, oxygenation, pulmonary radiography,
progression of pulmonary infiltrate, and culture of tracheal aspirate.(Appendix) A randomized
controlled trial allocated 81 patients to either an intervention group who received IV ciprofloxacin
and evaluation at 3 days with the CPIS score, where if the CPIS score was ≤6 the antibiotic was
stopped, or a control group who received therapy with physician-directed antibiotics.(3) There was
no significant difference between the groups with respect to mortality.(3) Patients in the
intervention group did have statistically fewer days on antibiotics, shorter ICU stays, and lower
incidence of antimicrobial resistance or super infections.(3)
Short Course Therapy for VAP
3. Appropriate single agent therapy is recommended for each potential pathogen as empiric therapy
for VAP, when appropriate for local resistance patterns.
The guidelines developed by the Critical Care Trials Group (1) also recommend appropriate single
agent therapy for each potential pathogen as empiric therapy for VAP. Based on 5 trials, they
were able to conclude that empiric broad-spectrum combination therapy had no advantage over
monotherapy with respect to differences in mortality or clinical response rates (1). This use of
monotherapy as recommended is another strategy for efficient use of antimicrobial therapy.
References
1. Muscedere J, Dodek P, Keenan S, Fowler R, et al. Comprehensive evidence-based clinical
practice guidelines for ventilator-associated pneumonia: Diagnosis and Treatment. Journal of
Critical Care. 2008;23:138-47.
2. Chastre J, Wolff M, Fagon JY et al. Comparison of 8 vs. 15 Days of Antibiotic Therapy for
Ventilator-Associated Pneumonia in Adults: A Randomized Trial.
3. Singh N, Rogers P, Atwood C, et al. Short-course Empiric Antibiotic Therapy for Patients with
Pulmonary Infiltrates in the Intensive Care Unit. Am J Respir Crit Care Med. 2000;162:505511.
Acknowledgements:
ISMP Canada gratefully acknowledges the input provided by Laura Murphy, Pharm D and the expert
review by (to be determined).
Page 2 of 3
Short Course Therapy for VAP
Appendix
Clinical Pulmonary Infection Score Calculation (3)
Temperature (ºC)
≥ 36.5 and ≤ 38.4 = 0 points
≥ 38.5 and ≤ 38.9 = 1 points
≥ 39 and ≤ 36 = 2 points
Blood leukocytes,mm3
≥4000 and ≤ 11000 = 0 points
<4000 and > 11000 = 1 point + band forms ≥50% = add 1 point
Tracheal secretions
Absence of tracheal secretions = 0 points
Presence of nonpurulent tracheal secretions = 1 point
Presence of purulent tracheal secretions = 2 points
Oxygenation: Pa02/Fi02 mmHg
>240 or ARDS (ARDS defined as Pa02/Fi02 >200, pulmonary arterial wedge pressure
18mmHg and acute bilateral infiltrates) = 0 point
≤ 240 and no ARDS = 2 points
≤
Pulmonary radiography
No infiltrate = 0 point
Diffuse (or patchy) infiltrate = 1 point
Localized infiltrate = 2 points
Progression of pulmonary infiltrate
No radiographic progression = 0 points
Radiographic progression (after CHF and ARDS excluded) = 2 points
Culture of tracheal aspirate
Pathogenic bacteria* cultured in rare or light quantity or no growth = 0 point
Pathogenic bacteria cultured in moderate or heavy quantity = 1 point
Same pathogenic bacteria seen on Gram stain, add 1 point
Definition of abbreviations: ARDS = acute respiratory distress syndrome; CHF = congestive heart
failure; Pa02/Fi02 = ratio of arterial oxygen pressure to fraction of inspired oxygen.
*Predominant organism in the culture
Page 3 of 3
Ontario Antimicrobial Stewardship Project
Evidence-Based Summary for Short-Course Antimicrobial Therapy:
Intra-abdominal Infection
1. In patients with acute intra-abdominal infections requiring surgery appropriate duration of
antibiotic therapy ranges from 1 day (e.g. simple appendectomy, diverticulitis, cholecystitis, early
bowel trauma) to 5 days (e.g. perforated appendix, gastroduodenal perforation).
A study stratified 163 patients who underwent emergency abdominal surgery for suspected intraabdominal infection into four groups based on postoperative findings (1). Group 1 (n=60) received
only a single dose of prophylaxis antibiotics for ‘simple’ acute appendicitis, cholecystitis or
diverticulitis, ‘early’ (i.e. less than 12 h) traumatic bowel lesions and gastroduodenal perforations,
or ischaemic/strangulated ‘dead’ bowel without frank perforation. Group 2 (n=32) received 24 hour
treatment for gangrenous appendicitis, gallbladder necrosis or empyema, and presented with no
free pus. Group 3 (n=48) received 48 hour treatment for intra-abdominal infection from diverse
sources with localized pus formation, ‘late’ (i.e. more than 12 h) traumatic bowel lesions and
gastroduodenal perforations. Finally, Group 4 (n=23) received 3-5 day treatment for diffuse
"established" purulent peritonitis from all sources. Patients were treated with ampicillin 1 g plus
gentamicin 120 mg plus metronidazole 500 mg, or ceftriaxone 1 g plus metronidazole 500 mg in
patients with raised urea or creatinine level. Exclusions included patients with negative
laparotomy findings, intestinal obstruction with viable bowel and the need for planned
relaparotomy or laparostomy (postoperative or diffuse faecal intraabdominal infection and
pancreatitis-related infection). These patients had a mean APACHE II score of 7 (range 0-16) and
mean age 42 (range 24-84). Persistent or recurrent intra-abdominal infection occurred in two
patients (anastomotic leakage in one; subhepatic abscess drained percutaneously in the other),
and occurred in groups 3 and 4 (one in each). Additional antibiotic therapy was required in 17
patients (10 %), most often due to pneumonia and other causes un-related to intra-abdominal
infection. One patient died in each of groups 2, 3 and 4 (overall 2% in study) following
relaparotomy for an anastomotic leak, a myocardial infarction and aspiration pneumonia. In the
groups described above, duration of antibiotic therapy for less than 5 days was sufficient in most
cases.
2. In patients with perforated appendicitis, gastroduodenal perforation, small bowel necrosis or
peritonitis (from any source), it is appropriate to treat with 5 days of antibiotic therapy:
A study stratified 381 patients to different durations of prophylactic antimicrobial treatment in
emergency abdominal surgery, based on diagnosis (2). Patients with acute appendicitis received
only perio-perative antibiotics (n=55). Patients with gangrenous appendicitis (n=92), gangrenous
cholecystitis (n=18) and small/large bowel obstruction (n=52) received antibiotic treatment for 24
hours. Patients with perforated appendicitis (n=53), gastroduodenal perforations (n=17), small
bowel necrosis (n=3) and peritonitis (from any source, n=84) received antibiotics for 5 days.
Patients were treated with gentamicin 160 mg, and then 80 mg q8h combined with metronidazole
500 mg q8h or fosfomycin 4 g q6h with metronidazole 500 mg q8h. Success rates in the patients
treated for 24 hours were 98-100% in patients with acute appendicitis or gangrenous
appendicitis/cholecystitis. Success rate was 90% in patients with small/large bowel obstructions.
Success rates in perforated appendicitis were 94%, gastroduodenal perforation 88%, small bowel
necrosis 100%, and peritonitis 93%. The study , although not a randomized controlled trial and
consisting of a small sample size, is one of the few studies to examine duration, and confirm that
less-complicated intra-abdominal infections require treatment for 24 hours. More complicated
infections that carry an increased risk for septic complications such as perforated appendicitis,
can be successfully treated with total duration of 5 days.
Short Course Therapy for Intra-abdominal Infection
References:
1. Schein M, Assalia A, Bachus H. Minimal antibiotic therapy after emergency abdominal
surgery: a prospective study. Br J Surg 1994;81:989–991
2. Andäker L, Höjer H, Kihlström E, et al. Stratified duration of prophylactic antimicrobial
treatment in emergency abdominal surgery. Metronidazole-fosfomycin vs. metronidazolegentamicin in 381 patients. Acta Chir Scand 1987;153:185–192.
3. Mazuski JE, Sawyer RG, Nathens AB, et al. The Surgical Infection Society Guidelines on
Antimicrobial Therapy for Intra-Abdominal Infections: Evidence for the Recommendations.
Surgical Infections; Volume 3, Number 3, 2002.
Acknowledgements:
ISMP Canada gratefully acknowledges the input provided Alina Varghese Pharm D and the expert
review by (to be determined).
Page 2 of 2
Ontario Antimicrobial Stewardship Project
Evidence-Based Summary for Short-Course Antimicrobial Therapy:
Surgical Prophylaxis
1. A single dose of prophylactic IV antibiotic should be delivered 15 – 60 minutes pre-operatively.
For prolonged surgeries (> 4 hours) re-dosing may be needed to maintain adequate tissue
concentrations. Post-operative antibiotic prophylaxis is not beneficial and is not recommended.
In a systematic review of randomized trials in major surgeries, there was no difference in the rate
of surgical site infection (SSI) with single dose compared to multiple dose regimens given for less
than or more than 24 hours (combined odds ratio 1.04, 95% CI 0.86-1.27) [1]. The majority of
published evidence demonstrates that antimicrobial prophylaxis after incision closure is
unnecessary [2,3]. In addition to the lack of benefit of additional doses, prolonged use of
prophylactic antimicrobials is associated with the emergence of resistant bacterial strains [2]. The
prophylactic antimicrobial should be administered as near to the incision time as possible to
achieve low SSI rates [2]. A prospective study demonstrated that administering prophylactic
antibiotics within two hours before surgery was associated with the lowest risk of SSI [4]. Based
on the available evidence, infusion of the first antimicrobial dose should begin within 60 minutes
before incision [2]. If the procedure is prolonged (> 4 hours), re-dosing every 1-2 half-lives of the
antimicrobial should provide adequate drug concentrations during the procedure [2].
2. The appropriate prophylactic antimicrobials targeting the most likely offending organisms should
be selected for the type of surgery, taking into consideration the current recommendations in the
literature, issues of resistance and patient allergies.
An effective prophylactic regimen should be directed against the most likely infecting pathogens.
There is little evidence to suggest that the newer antimicrobials with broader antibacterial activity
result in lower rates of SSI [5]. For most procedures, a first-generation cephalosporin such as
cefazolin is active against the predominant staphylococci and streptococci pathogens. For
procedures involving exposure to bowel anaerobes such as Bacteroides fragilis, addition of an
agent with activities against bowel anaerobes is recommended. In patients with life-threatening
allergies to beta-lactam antibiotics, vancomycin or clindamycin can be used as alternatives.
Aminoglycosides or fluoroquinolones may be added for activities against gram-negative
organisms [6]. The choice of antibiotic should take into account local resistance patterns [2, 5, 6].
Guidelines for the selection of appropriate prophylactic antimicrobials for various procedures are
available [5-9].
References
1. McDonald M, Grabsch E, Marshall C, Forbes A. Single- versus multiple-dose antimicrobial
prophylaxis for major surgery: a systematic review. Aust N Z J Surg 1998;68:388-396.
2. Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the
National Surgical Infection Prevention Project. Clin Infect Dis 2004;38:1706-15.
3. Scher KS. Studies on the duration of antibiotic administration for surgical prophylaxis. Am
Surg 1997;63:59-62.
Short Course Therapy for Surgical Prophylaxis
4. Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP. The timing of
prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J
Med 1992; 326:281–6.
5. American Society of Health-System Pharmacists. ASHP therapeutic guidelines on
antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 1999; 56:1839–88.
6. Antimicrobial prophylaxis for surgery. Treat Guide Med Lett 2006;4:83-88.
7. Engelman R, Shahian D, Shemin R, Guy TS, Bratzler D, Edwards F, Jacobs M, Fernando H,
Bridges C, Workforce on Evidence-Based Medicine, Society of Thoracic Surgeons. The
Society of Thoracic Surgeons practice guideline series: Antibiotic prophylaxis in cardiac
surgery, part II: Antibiotic choice. Ann Thorac Surg 2007;83:1569-76.
8. American Academy of Orthopaedic Surgeons. Recommendations for the Use of intravenous
Antibiotic Prophylaxis in Primary Total Joint Arthroplasty 2004. Available at:
http://www.aaos.org/. Accessed on Sep 20, 2008.
9. ACOG Practice Bulletin No. 74: Antibiotic Prophylaxis for Gynecologic Procedures. Obstet
Gynecol 2006; 108:225.
Acknowledgements:
ISMP Canada gratefully acknowledges the input provided by Monica Lee Pharm D, MSc and the
expert review by (to be determined).
Page 2 of 2
Ontario Antimicrobial Stewardship Project
Evidence-Based Summary for Short-Course Antimicrobial Therapy:
Uncomplicated Urinary Tract Infection
A 3-day course of antibiotics is appropriate in adult women with acute lower uncomplicated UTI.
Treatment of asymptomatic bacteriuria in non-pregnant women is not required.
Evidence indicates 3 days of antibiotics for acute lower (bladder and ureters) uncomplicated (not
catheterized or obstructed) UTI in females has similar clinical outcomes to 5 or more days of
antibiotics. Currently, ISDA guidelines support the use of 3-day antibiotic treatment in uncomplicated
UTI in women <65 years of age1. Single-dose treatment is no longer used as analyses indicate this
ultra-short duration is associated with higher rates of bacteriological recurrence2. Males generally
experience complicated UTIs and there is insufficient data to support short-course treatment in this
population.
A 2005 Cochrane Collaboration meta-analysis3 comparing effectiveness of various antibiotics used
for 3 days with 5 or more days of antibiotic in females 16 to 65 years of age included data from >
9000 patients enrolled in 32 trials (between 1980 and 2000). No difference between 3-day and > 5day treatment was found for short-term symptomatic or bacteriologic failure (RR = 1.06, 95% CI =
0.88 – 1.28, RR = 0.92, 95% CI = 0.80 – 1.06 respectively) by intention-to-treat (ITT) analysis. Also,
there was no significant difference between 3-day and > 5-day regimens with respect to recurrence
rates at 8 weeks (RR 1.90, 95% CI = 0.94-1.27). When separate classes of antibiotics were
compared, the lack of difference in failure rates remained in the short-term symptomatic failure
analysis.
Recently, a prospective, randomized open-label trial in 455 pre-menopausal women over 18 years of
age compared ciprofloxacin 250mg po q12h x 3 days to TMP/SMX 160/800mg po q12h x 7 days to
norfloxacin 400mg po q12h x 7 days4. Results indicated short-term symptomatic and bacteriological
failure rates were similar between the 3 groups at 5-9 days after antibiotics, as were late recurrence
rates of symptoms or bacteriuria at 6-8 weeks after antibiotics.
The Cochrane Collaboration performed a meta-analysis comparing the effectiveness of various
antibiotics used for 3-6 days with 7 or more days of antibiotic in females over 60 years of age5.
Endpoints examined failure rates in terms of clinical symptoms and bacteriuria.
Results included data from 15 trials eligible for inclusion published between 1981 and 2005. The
authors do not state the number of total number of subjects in these trials but it appears to be >1000.
The analysis concluded: Clinically symptomatic failure rates were no different between the short and
long-course groups. RR = 0.98, 95% CI=0.62-1.54 and bacteriologic failure rates were not
significantly different between the two different duration groups at 2 weeks (RR = 0.85, 95% CI= 0.292.47) or longer (RR = 0.85, 95% CI=0.54-1.32).
Asymptomatic bacteriuria with pyuria is not an indication for antibiotic treatment according to ISDA
guidelines. The only exceptions are pregnancy and perhaps short-term catheterization where
bacteriuria has persisted for more than 48 hours after catheter removal6.
Short Course Therapy for Uncomplicated Urinary Tract Infection
References:
1. Warren JW et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis
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Acknowledgements:
ISMP Canada gratefully acknowledges the input provided by Katrina Mulherin PharmD and the expert
review by (to be determined).
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