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