ICMR Antimicrobial guidelines for prophylaxis and treatment of Surgical Site Infections

Surgical site infections (SSIs) are one of the most common health care associated infections (HCAIs) and represent a substantial cause of morbidity with 2-11-fold higher mortality. Patients developing SSIs are 60% more likely to be admitted to an ICU, are more than five times more likely to be readmitted to the hospital, and are twice as likely to die as similar patients without SSIs. SSIs complicate 3,00,000-5,00,000 surgeries per year in the USA alone, and are believed to result in US$5-10 billion of excess health expenditures, with 7- 10 days of increased length of hospital stay. SSI rates have become a universal measure of quality in hospital-based surgical practice, since they are probably the most preventable type of HCAI.

Peri-operative antimicrobials administered as prophylaxis for SSIs account for the majority of in-hospital antimicrobial prescriptions. Usually, long courses of antibiotic prophylaxis are administered, which are often associated with increasing antimicrobial resistance, super-infection with resistant pathogens, toxicity and unnecessary cost. Rampant and unnecessary administration of antibiotics is one of the major contributors for development of drug resistance.

In a systematic review on antibiotic prophylaxis for surgery for proximal femoral and other closed long bone fractures, a single dose antibiotic prophylaxis was found to significantly reduce the risk of deep surgical site infections. Several studies have justified the use of short courses of a single cephalosporin for clean surgeries, since these act on the most likely organisms causing SSIs.

Indian Council of Medical Research, Department of Health Research has issued the ICMR Antimicrobial guidelines for prophylaxis and treatment of Surgical Site Infections. Following are the major recommendations :

Case definitions

Surgical Wound Classification

• Class I/Clean: uninfected operative wound in which no inflammation is encountered & respiratory, alimentary, genital, or uninfected urinary tract is not entered. Operative incisional wounds following blunt trauma are included here.


• Class II/ Clean-Contaminated: Operative wound in which the respiratory, alimentary, genital, or urinary tracts are entered under controlled conditions and without unusual contamination.


• Class III/Contaminated: Open, fresh, accidental wounds. Operations with major breaks in sterile technique or gross spillage from the GIT.


• Class IV/Dirty-Infected: Old traumatic wounds with retained devitalized tissue and those that involve existing clinical infection or perforated viscera.

Table 1 Criteria for Defining a Surgical Site Infection (SSI)CDC ; ref 1

Superficial Incisional SSI Infection occurs within 30 days after the operation and infection involves only skin or subcutaneous tissue of the incision and at least one of the following: Purulent drainage, with or without laboratory confirmation, from the superficial incision. Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision. At least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or heat and superficial incision is deliberately opened by surgeon, unless incision is culture-negative. Diagnosis of superficial incisional SSI by the surgeon or attending physician. Do not report the following conditions as SSI: Stitch abscess (minimal inflammation and discharge confined to the points of suture penetration). Infection of an episiotomy or newborn circumcision site. Infected burn wound. Incisional SSI that extends into the fascial and muscle layers (see deep incisional SSI). Note: Specific criteria are used for identifying infected episiotomy and circumcision sites and burn wounds. Deep incisional SSI Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is in place and the infection appears to be related to the operation and infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision and at least one of the following: Purulent drainage from the deep incision but not from the organ/space component of the surgical site. A deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has at least one of the following signs or symptoms: fever (>38ºC), localized pain, or tenderness, unless site is culture-negative. An abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation, or by histopathologic or radiologic examination. Diagnosis of a deep incisional SSI by a surgeon or attending physician. Notes: Report infection that involves both superficial and deep incision sites as deep incisional SSI. Report an organ/space SSI that drains through the incision as a deep incisional SSI Organ/space SSI Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is in place and the infection appears to be related to the operation and infection involves any part of the anatomy (e.g., organs or spaces), other than the incision, which was opened or manipulated during an operation and at least one of the following: Purulent drainage from a drain that is placed through a stab wound into the organ/space. Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space. An abscess or other evidence of infection involving the organ/space that is found on direct examination, during reoperation, or by histopathologic or radiologic examination. Diagnosis of an organ/space SSI by a surgeon or attending physician.

Table 2 Operations and Likely Surgical Site Infection (SSI) Pathogens

Operations	Likely Pathogens
Placement of all grafts, prostheses, or implants	Staphylococcus aureus; Coagulase negative Staphylococci (CoNS)
Cardiac	Staphylococcus aureus; CoNS
Neurosurgery	Staphylococcus aureus; CoNS
Breast	Staphylococcus aureus; CoNS
Ophthalmic	S. aureus; CoNS; streptococci; gram negative bacilli (GNBs)
Orthopedic: Total joint replacement, closed fractures/use of nails, bone plates, other internal fixation devices, functional repair without implant/device, Trauma	Staphylococcus aureus; CoNS; gram-negative bacilli
Noncardiac thoracic, Thoracic (lobectomy, pneumonectomy wedge resection, other noncardiac mediastinal procedures), closed tube thoracostomy	Staphylococcus aureus; CoNS; Streptococcus pneumoniae; gram-negative bacilli
Vascular	Staphylococcus aureus; CoNS
Appendectomy	Gram-negative bacilli; anaerobes
Biliary tract	Gram-negative bacilli; anaerobes
Colorectal	Gram-negative bacilli; anaerobes
Gastroduodenal	GNBs; streptococci; oropharyngeal anaerobes (e.g.,peptostreptococci)
Head and neck (major procedures with incision through oropharyngeal mucosa)	Staphylococcus aureus; streptococci; oropharyngeal anaerobes (e.g., peptostreptococci)
Obstetric and gynecologic	GNBs; enterococci; group B streptococci; anaerobes
Urologic	Gram-negative bacilli

Investigations

Samples:

• Pus in sterile, wide mouth screw cap containers (if deep seated abscess, collect samples in anaerobic vials also)


• If pus is not available, wound swabs (deep swabbing)

Samples should be taken from the depth of the wound or the advancing edge, avoiding contamination from surrounding skin.

Transport: Immediate transport to the lab

Culture:

• Aerobic: Blood agar, Mac Conkey agar, 37 0 C in air


• Anaerobic: Brain Heart Infusion agar with hemin and vitamin K (anaerobic incubation): 37 0 C, under anaerobic conditions


• Fungal culture (if needed as in obvious contamination with soil etc): SDA with appropriate antibiotics/ BHI-BA with appropriate antibiotics and incubation temperatures (25 and/or 37 degrees)

Resistance pattern of common pathogens (ICMR Data)

Following is the Indian data of AMR from soft tissue infections/SSI

Table 3 Staphylococcus aureus ICMR AMR Data 2014

*The 4 numbers listed as Vancomycin Resistant (R) are VISA isolates; No VRSA was isolated during the year 2014 at JIPMER.; Cefoxitin : Surrogate marker for Methicillin.

Table 1Enterobacteriaceae isolates from skin and soft tissue. ICMR data 2014.

Note: Ec: Escherichia coli; Ks : Klebsiella spp; Es : Enterobacter spp.

Table 2 Pseueudomonas aeruginosa ICMR AMR data 2014

AMA	PGIMER, Chandigarh 'n' 75 R (%)	AIIMS, New Delhi 'n' 102 R (%)	JIPMER, Puducherry 'n' 113 R (%)	CMC, Vellore 'n' 84 R (%)	National 'n' 374 R %
Amikacin	27	49	38	21	35
Aztreonam		62	55	30	48
Cefepime		52	57	20	41
Cefoparazon e-sulbactam		39	41	30	38
Ceftazidime	64	51	51	23	47
Colistin		34		2	10
Imipenem	17	54	48	25	37
Levofloxacin		44	42	23	36
Meropenem		74	41	23	47
Netilmicin		66	45	22	45
Piperacillin-tazobactam	44	67		25	46
Tobramycin		56	43	18	33

Perioperative prophylaxis

Choosing prophylactic antibiotics

• Antibiotics should be chosen on the basis of their effectiveness against the pathogens most likely to be encountered rather than against every possible pathogen. Skin florae (eg, Staphylococcus organisms) are the usual target, so first-generation cephalosporins are recommended (cephalexin, cephalothin) in most studies. Few studies also recommend cefuroxime.


• Patients with a history of anaphylaxis or urticaria after penicillin therapy should not receive prophylaxis with a beta-lactam antibiotic. Vancomycin or clindamycin should be used as alternative.

Timing of prophylactic antibiotics

• Give first dose before incision


• Antibiotics should be administered before an incision is made to ensure that antimicrobial levels in the tissue are adequate and maintained for the duration of the procedure.


• Prophylaxis should be started preoperatively in most circumstances, ideally within 30-60 minutes before incision, except for Vancomy

Route of administration

• Prophylactic antibiotics for surgical procedures should be administered intravenously

Dose selection

• The dose of an antibiotic for prophylaxis is same as for therapy of infection.

Duration

• Continue no longer than 24 hours postoperatively (Except cardiac surgery where data is conflicting)


• Most studies have demonstrated efficacy of postoperative antibiotic prophylaxis for only 12 hours or less. Whenever short and long courses are compared, the shorter course has proven equally effective. A single dose is as effective as multiple doses, and antimicrobial prophylaxis after wound closure is unnecessary.


• Prolonged antibiotic prophylaxis beyond 24 hours is not only ineffective in reducing infections but increases antimicrobial resistance and the risk of colitis due to Clostridium difficile.

Redose for longer surgeries

• Patients undergoing surgery that extends beyond two half-lives of an antibiotic should be re-dosed intraoperatively.


• An additional dose of prophylactic agent is not indicated in adults, unless there is blood loss of up to 1500 ml during surgery or haemodilution of up to 15 ml/kg.

Table 3 Pathogen-specific antimicrobial therapy according to the pathogen isolated

Surgical Wound Classification	Common Organisms	Antimicrobial prophylaxis
Class I/Clean	Gram Positive cocci (S. aureus, CoNS)	None or single perioperative dose of cefuroxime/ cephalexin (Ideally 2 grams)
Class II/ Clean-Contaminated	Gram Negative Bacilli Anaerobes S. aureus	1stLine: Cefazolin or Ampicillinsulbactam or Ceftriaxone (in patients of acute cholecystitis or acute biliary tract infections) Alternative: In case of allergies; if mixture of GP and GN is suspected: Ceftriaxone only if not ESBL clindamycin or vancomycin with cefazolin, aztreonam, gentamicin, or single-dose fluoroquinolone in blactam allergic
Class III/Contaminated	Gram Negative Bacilli Anaerobes	1st line: Cefazolin + Metronidazole 2nd Line: Metronidazole+ Aminoglycoside/ Fluoroquinolone
Class IV/Dirty-Infected	Gram Negative Bacilli Anaerobes May be mixed with Gram positive bacteria	1st Line: Cefazolin + metronidazole, Treatment for infected surgical wounds Ertapenem + Clindamycin + aminoglycoside/aztreonam Or fluoroquinolone+ metronidazole + aminoglycoside/fluoroquinolone

Table 4 Antibiotics for Treatment of Incisional Surgical Site Infections In culture confirmed cases of SSI/ soft tissue infections, antimicrobials should be based on Lab AST reports

Surgery	Common organisms	Peri-op antimicrobial prophylaxis
Surgery of Intestinal or Genitourinary Tract	Gram Negative Bacilli, anaerobes	1st Line: Piperacillin-tazobactam 3.375 g every 6 h or 4.5 g every 8 h IV Or Imipenem-cilastatin 500 mg every 6 h IV 2nd Line (as in case of non ESBL organisms) : Ceftriaxone 1 g every 24 h + metronidazole 500 mg every 8 h IV
Surgery of trunk or extremity away from axilla or perineum	S. aureus, CoNS	1st Line: Oxacillin/ nafcillin 2 g every 6 h IV Or Cefazolin 0.5–1 g every 8 h IV 2nd Line: Cefotaxime 500 mg every 6 h IV
Surgery of axilla or perineum	S.aureus, GNBs, anaerobes	1st Line: Metronidazole 500 mg every 8 h IV plus Levofloxacin 750 mg every 24 h 2nd Line: Metronidazole 500 mg every 8 h IV plus Ceftriaxone 1 g every 24 h

Table 5 Antimicrobial guidelines for treatment of Skin and Soft Tissue Infections

Clinical Syndrome/ condition	Most likely pathogens	Antibiotic	Comments
Impetigo and skin soft-tissue infections	Staphylococci & Streptococci	1st Line Clindamycin 300-400 mg qid PO Alternative: Amoxicillin-clavulanate 875/125 mg bid po	Local: Mupirocin ointment Apply to lesions bid
Erysipelas, Cellulits, Necrotising fasciitis	Streptococci (usually GAS)	Penicillin 2–4 million units X 4–6 h IV or Alternative Clindamycin 600–900 mg X 8 h IV	In penicillin allergic patients: Clindamycin, vancomycin or linezolid,
Cutaneous anthrax	Bacillus anthracis	1st Penicillin G8–12 MU/day IV in divided doses every 4-6 h or Erythromycin 250 mg PO every 6 hours
Necrotizing infections of the skin, fascia, and muscle	Mixed infections	1st Line Piperacillin-tazobactam + Vancomycin 3.37 g every 6–8 h IV+ 30 mg/kg/d in 2 divided doses Alternative Carbapenems
Water related injuries (water sports etc)	Aeromonas hydrophila Vibrio vulnificus	Doxycycline100 mg every 12 h IV+ ciprofloxacin500 mg every 12 h IV or Ceftriaxone1 to 2 g every 24 h IV
Bubonic plague Diabetic Foot Infections	Yersinia pestis	1st Line Streptomycin 1 g IM twice per day or Gentamicin 2 mg/kg loading dose, then 1.7 mg/kg/day in 3 divided doses IV Alternative Tetracycline 500 mg po every 6 h
Mild (treated with oral agents)	MSSA; Streptococcus spp	Cloxacillin/ cephalexin
	MRSA	Linezolid, Daptomycin, Vancomycin
Moderate (treated with oral or initial parenteral agent) or severe (treated with parenteral agents)	MSSA; Streptococcus spp; Enterobacteriac eae; obligate anaerobes	Ceftriaxone, Ampicillin/sulbactam, Moxifloxacin, Ertapenem, Tigecycline

Table 6 Standard Doses of Antimicrobial Agents Active Against Multidrug Resistant Organisms

Antimicrobial	IV Dose	Comments
Vancomycin	30–60 mg/kg/d in 2–4 divided doses	Target serum trough concentrations of 15–20 μg/mL in severe infections
Daptomycin	4–6 mg/kg/d	Covers VRE, strains nonsusceptible to vancomycin may be cross-resistant to daptomycin
Linezolid	600 mg every 12 h	100% oral bioavailability; so oral dose same as IV dose. Covers VRE and MRSA
Colistin	5 mg/kg load, then 2.5 mg/kg every 12 h	Nephrotoxic; does not cover gram-positives or anaerobes, Proteus, Serratia, Burkholderia

Guidelines by Indian Council of Medical Research :

Dr Soumya Swaminathan, Director General, Indian Council of Medical Research Secretary, Department of Health Research