Post on 08-Jan-2017
Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery
By : Somayyeh Nasiripour ,Pharm.D-Ph.D Assistant professor of clinical pharmacy
at IUMS
These guidelines were developed jointly by :
• the American Society of Health-System Pharmacists (ASHP),
• the Infectious Diseases Society of America (IDSA),
• the Surgical Infection Society (SIS),• the Society for Healthcare Epidemiology of
America (SHEA).
Preoperative-dose timing.
optimal time for administration of preoperative doses is within 60 minutes before surgical incision
fluoroquinolones and vancomycin within 120 minutes before surgical incision Because these drugs have long half-lives, this early administration should not compromise serum levels of these agents during most surgical procedures
• For all patients, intraoperative redosing is needed to ensure adequate serum and tis- sue concentrations of the antimicrobial if the duration of the procedure exceeds two half-lives of the drug or there is excessive blood loss during the procedure
• Cefazolin : 2 gr• Ceftriaxone : 2 gr• Ciprofloxacin : 400 mg• Metronidazole : 500 mg• Piperacillin– tazobactam : 3.75• Ampicillin–sulbactam : 3 gr (2+ 1) • Clindamycin: 900 mg
Fixed
dose
• Vancomycin : 15 mg /kg • Gentamicing : 5 mg /kg
Mg /kg
gentamicin will be used in combination with a parenteral antimicrobial
with activity against anaerobic agents for prophylaxis,
use 4.5–5 mg/kg as a single dose (IBW)
This dose of gentamicin has been found safe and effective in a large
body of literature examining the use of single daily doses of gentamicin
for therapeutic indications.
When used as a single dose for prophylaxis, the risk of toxicity from
gentamicin is very low.
How we calculate dose in obese patients
pharmacokinetics of drugs may be altered in obese patients, so dosage
adjustments based on body weight may be warranted in these patients.
Distribution (VD)
• The volume of distribution (Vd) is a theoretical volume in which a drug amount uniformly distributes to produce the desired plasma concentration.
• Vd = dose / C Dose = Vd* C
• Vd is affected by the medication properties including lipophilicity, hydrophilicity, plasma protein binding, and molecular weight,size of body , blood circulation
• Obesity increases Vd, especially for lipophilic antibiotics, because of increased lean body mass and increased adipose tissue which can lead to lower than expected plasma antibiotic concentrations
• In general Vd of hydrophilic drug related to LBW lipophilic drug related to TBW
• Vd is nessassary for LD LD= Vd *C/ F
AG
• Vd in obesity will be increased to 9-58%
• IBW underestimate Vd • TBW overestimate Vd• ABW= IBW + [ 0.4 * (TBW- IBW)]
Better to use ABW
gentamicin for surgical antibiotic prophylaxis should be limited to a single dose given
preoperatively.
Dosing is based on the patient’s actual body weight.
If the patient’s actual weight is more than 20% above ideal body weight (IBW), the dosing
weight (DW) can be determined as follows:
DW = IBW + 0.4(actual weight – IBW).
Vancomycin
• Vd in obesity will be increased to 13-49%• Cl will be increase in obese person to 131-
156%• clinical trials are shown using TBW is a better
predictor for Vd & CL
• In obesity interval q 8 hr • Obesity + GFR < 60 TDM
cefazoline
• Use fixed dose 3 gr if W >/ 120 kg
does Dose adjustment need for
prophylaxis ?????
No
patients with renal or hepatic dysfunction, antimicrobial prophylaxis often
does not need to be modified for these patients when given as a single
preoperative dose before surgi cal incision.
Redosing during surgeryif the duration of the procedure exceeds two half-lives of the antimicrobial or
there is excessive blood loss (i.e., >1500 mL).
Eg: cefazolin q 4 hr When vancomycin is used almost always single dose due to its long half-life.
The redosing interval should be measured from the time of administration of the
preoperative dose, not from the beginning of the procedure
Redosing may also be warranted if there are factors that shorten the half-life of the antimicrobial agent
(e.g., extensive burns).
Redosing may not be warranted in patients in whom the half-life of the antimicrobial agent is prolonged
(e.g., patients with renal insufficiency or renal failure)
Duration of prophylaxis
single dose or continuation for less
than 24 hours
The use of standardized antimicrobial order sets, automatic stop-order
programs, and edu cational initiatives has been shown to facilitate the
adoption of guidelines for surgical antimicrobial prophylaxis
Cardiothoracic proc dures for which a prophylaxis duration of up to 48 hours has been accepted without
evidence to support the practice is an area that remains controversial
fluoroquinolones have
been associated with an
increased risk of
tendinitis/tendon rupture
in all ages, use of these
agents for single-dose
prophylaxis is generally
safe.
Which AB mostly used
cefazolin
exception
AppendectomySmall intestine obstructed
ColorectalHead and neck
OphtalmicUrologic
Liver trasplantation
Local resistance patterns should also be considered in selecting
antimicrobial agents and are discussed in the colonization and
resistance patterns section of the Common Principles section.
Although antimicrobial prophylaxis plays an important role in reducing the rate of SSIs, other
factors such as attention to basic infection-control strategies, the surgeon’s experience and
technique, the duration of the procedure, hospital and operating-room environments,
instrument- sterilization issues, preoperative preparation (e.g., surgical scrub, skin antisepsis,
appropriate hair removal), perioperative management (temperature and glycemic control), and
the underlying medical condition of the patient may have a strong impact on SSI rates.
but do not include a discussion of or any recommendations regarding these issues beyond the
optimal use of prophylactic antimicrobial agents.
Patient-related factors associated with an increased risk of SSI
• extremes of age, • nutritional status,• obesity, • diabetes mellitus, • tobacco use,• coexistent remote body-site infections, • altered immune response, corticosteroid therapy,• recent surgical procedure,• length of preoperative hospitaliza- • immunocompromised (e.g., malnourished, neutropenic,
receiving immunosuppressive agents).
Antimicrobial prophylaxis may be beneficial in surgical procedures associated
with a high rate of infection (i.e., clean-contaminated or contaminated
procedures) and clean procedures where there are severe consequences of
infection (e.g., prosthetic implants), even if infection is unlikely.
The use of antimicrobial agents for dirty procedures or established infections is
classified as treatment of presumed infection, not prophylaxis.
Ideally, an antimicrobial agent for surgical prophylaxis
• (1) prevent SSI,• (2) prevent SSI-related morbidity and mortality, • (3) reduce the duration and cost of health care • (4) produce no adverse effects, • (5) have no adverse consequences for the microbial flora of
the patient or the hospital. To achieve these goals, an antimicrobial agent should be
(1) active against the pathogens most likely to contaminate the surgical site,
(2) given in an appropriate dosage and at a time that ensures adequate serum and tissue
concentrations during the period of potential contamination,
(3) safe
(4) administered for the shortest effective period to minimize adverse effects, the development
of resistance, and costs
For most procedures, cefazolin is the drug of choice
for prophylaxis
most widely studied antimicrobial agent, with proven
eficacy,desirable duration of action, spectrum of activity against
organisms commonly encountered in surgery, reasonable safety, and
low cost.
There is little evidence to suggest that broad-spectrum antimicrobial agents) result in lower
rates of postoperative SSI compared with older antimicrobial agents with a narrower
spectrum of activity
Common Surgical Pathogens • The predominant organisms causing SSIs after clean
procedures are skin flora, including S. aureus and coagulase-negative staphylococci (e.g., Staphylococcus epidermidis).
• In clean-contaminated procedures, including abdominal procedures and heart, kidney, and liver transplantations, the predominant organisms gramnegative rods and enterococci in addition to skin flora.
• S. aureus was the most common pathogen, • proportion of SSIs caused by S. aureus increased to 30%, with
MRSA comprising 49.2% of these isolates. • MRSA infections were associated with higher mortality rates,
longer hospital stays, and higher hospital costs compared with other infections.
Vancomycin
• Routine use of vancomycin prophylaxis is not recommended for any procedure • Vancomycin prophylaxis should be considered for patients with known MRSA
colonization or at high risk for MRSA colonization in the absence of surveillance data (e.g., patients with recent hospitalization, nursing-home residents, hemodialysis patients
Although vancomycin is commonly used when the risk for MRSA is high,
data suggest that vancomycin is less effective than cefazolin for
preventing SSIs caused by methicillin-susceptible S. aureus (MSSA)
For this reason, vancomycin is used in combination with cefazolin at
some institutions with both MSSA and MRSA SSIs
When vancomycin is used almost always single dose due to its long half-life.
prophylaxis in a patient with past infection or colonization with a resistant AB
• logical to provide prophylaxis with active against MRSA • specific prophylaxis for a resistant gr - pathogen in a patient with past
infection or colonization with such a pathogen may not be necessary for a purely cutaneous procedure.
• a patient colonized with vancomycin-resistant enterococci (VRE) should receive prophylaxis effective against VRE when undergoing liver transplantation but probably not when undergoing an umbilical hernia repair without mesh placement
For procedures in which pathogens other than staphylococci and streptococci are likely, an additional agent with
activity against those pathogens should be considered.
For example, if there gram-negative organisms are a cause of SSIs : vancomycin +cefazolin
vancomycin +aminoglycoside or single-dose fluoroquinolone if the patient has a β-lactam allergy)
Patients receiving therapeutic antimicrobials
• also be given antimicrobial prophylaxis before surgery to ensure adequate serum and tissue levels of antimicrobials with activity against likely pathogens for the duration of the operation
• If the agents used therapeutically are appropriate for surgical prophylaxis, administering an extra dose within 60 minutes before surgical incision is sufficient
For patients with indwelling tubes or drains,
• consideration may be given to using prophylactic agents active against pathogens found in these devices before the procedure
• even though therapeutic treatment for pathogens in drains is not indicated at other times
chronic renal failure receiving vancomycin,
• a preoperative dose of cefazolin should be considered instead of an extra dose of vancomycin, particularly if the probable pathogens associated with the procedure are gram-negative
• In most circumstances, elective surgery should be postponed when the patient has an infection at a remote site.
Allergy to β-Lactam Antimicrobials.
• Because the predominant organisms in SSIs after clean procedures are gram- positive, the inclusion of vancomycin may be appropriate for a patient with a life-threatening allergy IgE mediated to β-lactam.
• Type 1 anaphylactic reactions to antimicrobials usually occur 30–60 minutes after administration
• Cephalosporins and carbapenems can safely be used in patients with an allergic reaction to penicillins that is not an IgE-mediated reaction (e.g. urticaria, bronchospasm) or exfoliative dermatitis (Stevens-Johnson syndrome, toxic epidermal necrolysis)
Preoperative Screening and Decolonization
• S. aureus is the most common pathogen causing SSIs (30% ) so screening is useful
• Anterior nasal swab cultures are most commonly used for preoperative surveillance, but screening additional sites (pharynx, groin, wounds, rectum) can increase detection rates
• When properly used, all of these techniques can identify MSSA and MRSA
• Screening has been advocated to both identify candidates for S. aureus decolonization and inform the selection of optimal prophyactic antimicrobials, such as the addition of vancomycin for those colonized with MRSA.
intranasal mupirocin
• FDA has approved intranasal mupirocin to eradicate MRSA nasal colonization in adult patients and health care workers.
• the use of intranasal mupirocin in nasal carriers of S. aureus decreases the rate of S. aureus infections esp in cardiac and orthopedic surgery patients.
• used for five days before the operation TDS . Most studies conclude that the use of preoperative intranasal mupirocin in colonized
patients is safe and potentially beneficial as an adjuvant to i.v. antimicrobial prophylaxis to
decrease the occurrence of SSIs.
While S. aureus resistance to mupirocin has been detected, raising concerns about the
potential for widespread problems with resistance from routine use of this agent, resistance
has only rarely been seen in the preoperative setting.
when decolonization therapy (e.g., mupirocin) is used
as an adjunctive measure to prevent S. aureus SSI,
surveillance of susceptibility of S. aureus isolated
from SSIs to mupirocin is recommended.
While universal use of mupirocin is discouraged,
specific recommendations for the drug’s use can be
found in the cardiac and orthopedic.
Thoracic Procedures
• in addition to SSIs, postoperative nosocomial pneumonia and empyema are of concern after thoracic procedures
• independent risk factors for pneumonia after thoracic procedures: extent of lung resection, intraoperative bronchial colonization,COPD, BMI of >25 kg/m2, induction therapy (chemotherapy, radiotherapy, or chemoradiotherapy), ad- vanced age (≥75 years old), and stage III or IV cancer.
• S. aureus and S. epidermidis.
• a single dose of cefazolin or ampicillin– sulbactam is recommended • Vancomycin should be used for prophylaxis in patients known to be colonized with MRSA
• risk of gram-negative contamination of the surgical site, practitioners should combine clindamycin or vancomycin with another agent (cefazolin )
single dose of cefazolin or ampicillin– sulbactam is recommended
Gastroduodenal Procedures
• Patients who are at highest risk :
• those with achlorhydria, including : pharmacotherapy with H2 blocker / PPI, gastroduodenal perforation, decreased gastric motility, gastric outlet obstruction, morbid obesity, gastric bleeding, or cancer
• long procedure duration• emergency proce dures• greater than normal blood loss• late administration of antimicrobials.
• Antimicrobial prophylaxis in gastroduodenal procedures should be considered for patients at highest risk :including risk factors such as increased gastric pH (e.g., patients receiving acid- suppression therapy), gastroduodenal perforation, decreased gastric motility, gastric outlet obstruction, gastric bleeding, morbid obesity,, and cancer.
• A single dose of cefazolin
Biliary Tract Procedures
• Antimicrobial prophylaxis is not necessary in low-risk patients undergoing elective laparoscopic cholecystectomies.
• Antimicrobial prophylaxis is recommended in patients undergoing laparoscopic cholecystectomy who have an increased risk of infectious complications
Risk fac- tors include performance of emergency procedures, diabe- tes, anticipated procedure duration exceeding 120 minutes,
risk of intraoperative gallbladder rupture, age of >70 years, open cholecystectomy, risk of conversion of laparoscopic to open
cholecystectomy, ASA classification of ≥3, episode of biliary colic within 30 days before the procedure, reintervenion in less than
a month for noninfectious complications of prior biliary operation, acute cholecystitis, anticipated bile spillage, jaundice,
pregnancy, nonfunctioning gallbladder, and immunosuppression.
because some of these risk factors cannot be determined before the surgical
intervention, it may be reasonable to give a single dose of antimicrobial
prophylaxis to all patients undergoing laparoscopic cholecystectomy
Appendectomy Procedures
• anaerobic and aerobic gram-negative enteric organisms. Bacteroides fragilis is the most commonly cultured anaerobe, and E. coli is the most frequent aerobe,
For uncomplicated appendicitis, the recommended regimen is a single dose
of a cephalosporin with anaerobic activity (cefoxitin or cefotetan) or a single
dose of a first-generation cephalosporin (cefazolin) plus metroni- dazole
Small Intestine Procedures
• For small intestine procedures with no evidence of obstruction, a first-generation cephalosporin (cefazolin) is recommended.
• For patients with small intestine obstruction, a first-generation cephalosporin with metronidazole or a second-generation cephalosporin with anaerobic activity (cefoxitin or cefotetan) is the recommended agen
Hernia Repair Procedures
• single dose of a first-generation cephalosporin (cefazolin)
• For patients known to be colonized with MRSA, it is reasonable to add a single preoperative dose of vancomycin to the recommended agent.
Colorectal Procedures
• B. fragilis and other obligate anaerobes are the most frequently
• E. coli is the most common aerobe A single dose of second-generation cephalosporin with both aerobic and anaerobic
activities (cefoxitin or cefotetan) or cefazolin plus metronidazole is recommended
for colon procedures
In institutions where there is increasing resistance to first- and second- generation cephalosporins among gram-negative isolates from SSIs, the expert panel recommends a single dose of ceftriaxone plus metronidazole over routine use of car bapenems
alternative regimen is ampicillin–sulbactam
Oral regimens
• studies only when used with mechanical bowel preparation (MBP).
Erythromycin : 1 gr Metronidazol : 1 gr
Neomycin : 1 gr
Head and Neck Procedures
•thyroidectomy•lymph node excisions
Clean pro- cedures
• all procedures in volving an incision through the oral or pharyngeal mucosa, ranging from parotidectomy, submandibular gland excision, tonsillectomy, adenoidectomy, and rhinoplasty to compli cated tumor-debulking and mandibular fracture repair procedures requiring reconstruction.
Clean-contaminated
•No prophylaxis•if there is placement of prosthetic material, a preoperative dose of cefazolin or cefuroxime is reasonable,
Clean procedures
•cefazolin or cefuroxime plus metronidazole and•ampicillinsulbac- tam
Clean-contaminated procedures