ACTA FAC. MED. NAISS. 2003; 20 (2): 143-149

Review article

 

Antimicrobial  Prophylaxis  in  Surgical  Patients

 

Marjanović Vesna¹, Milićević Ružica¹, Marjanović Goran², Budić Ivana¹, Novaković Dejan¹, Marjanović Bojan³.

1 Department of Child Surgery and Orthopedics CC Nis

2 Department of Hematology CC Nis

3 Department of General Surgery CC Nis

Authors address

26/7 Sinđelicev trg, 18000 Nis

tel:  510160

 

e-mail: goranves@eunet.yu

 

 

            Summary

Nowadays antimicrobial prophylaxis represents a unique approach for reducing the incidence of wound infection associated with surgical procedures.  Recommendations for antimicrobial prophylaxis may be specific according to type of the procedure, causative agents, schedules and drug doses. It is important to note optimal timing of drug administration, and the optimal duration of prophylaxis in order to adjust maximal drug concentration in tissues that probably might be contaminated during the surgery. Currently it is recommended to receive antimicrobial prophylaxis at anesthesia induction as a short course that should have duration from 12-24 hours, while postoperative prophylaxis proved to be infective. The best route of administration is parenteral, while other routes are not so common. It is important to weigh costs of treatment of patients with developed postoperative wound infection who did not receive any prophylaxis, against cost and morbidity of patients who had received antimicrobial prophylaxis.

key words:  infection, antimicrobial prophylaxis, procedure.

            Introduction

The main objective of antimicrobial prophylaxis is to reduce the incidence of wound infection and not to minimize the importance of other measures designed to reduce bacterial contamination.

Attempts have been made to reduce appearance of postoperative infection particularly in clean-procedures in which contamination takes place. Incidence of postoperative infections reach 5% of all patients  undergoing surgery, with causative agents having exogenous origin (vascular access, catheters, ventilators, hospital air, hospital staff,  cleaning devices etc - all being easily eliminated following the principles of aseptic work) or endogenous pathogens, most commonly associated from the region of the body being operated upon. Significance of antimicrobial prophylaxis for surgical wound prevention is in reduction of endogenous and exogenous sources of contamination at the preoperative period.

 

Table 1. Clean contaminated procedures- part II

 

TYPE OF SURGERY	LIKELY PATHOGENS	RECOMMENDED ANTIMICROBIAL REGIMEN	COMMENTS
Appendectomy	Anaerobic organisms (especially B. fragilis) and gram negative enteric organisms (predominantly E. coli) Staphylococcus, Enterococcus and Pseudomonas species have also been reported.	Uncomplicated: Cefmetazole 1-2 gm IV preop. Complicated(adult): ampicillin 1-2 gm IV preop and gentamicin and metronidazole (for doses see bove)Complicated(children): ampicillin 50 mg/kg IV preop and gentamicin 2 mg/kg IV preop and clindamycin 10 mg/kg IV preop	The incidence of infectious complications following appendectomy is dependent on the condition of the appendix at the time of surgery. Gentamicin levels need to be monitored.
Hysterectomy   Vaginal	Staphylococci, streptococci, enterococci, lactobacilli, diph theroids, E. coli, peptostrepto cocci, Prevotella (Bacteroides), Porphyromonas(Bacteroides) and Fusobacterium species.	Cefazolin 1 gm IV at induction of anesthesia or Cefmetazole 1-2 gm IV	Postoperative infections are usually polymicrobial with enterococci, aerobic gram negative bacilli, and Bacteroides species isolated most frequently. For procedures greater than 4 hours, cefazolin may be administered. Highest risk hysterectomy procedure. Longer procedures may predispose patient to higher infection rates without prophylaxis. A bowel prep may be necessary, see the informat ion under colorectomy surgery. Increased risk factors such as length of surgery, blood loss, replacement, malignancy, prior radiation therapy, obesity and presence of drains postop.
Abdominal	Bacterial contamination associated with this procedure minimal.	Same as above.
Radical	Same as abdominal.	Same as above.
Cesarean section	Vaginal organisms as above if membranes ruptured. Post Cesarean infections include Staph aureus other staphylococci, streptococci and enterobacteriaceae.	Cefazolin 2 gm IV or Cefmetazole 2 gm IV	Highest risk factor is ruptured membranes which allows vaginal organisms to be drawn into the uterus between contractions. Prophylactic antibiotics should not be administered until the cord is clamped to decrease the risk to fetus. Cefmetazole is needed for Bacteroides fragilis coverage if the uterus may be contaminated by vaginal contents.

 

 

The standard should be implemented for antimicrobial prophylaxis in order to reduce rate of postoperative wound infection in conjunction with limitation on the cost of excessive use of antibiotics. (1,2). Current research is focused on determining the optimal antibiotic and optimal schedule and duration of prophylaxis necessary to reduce incidence of postoperative infections.

 

            Type of procedures and risk of infection

 

Today, conditions accepted for use of antimicrobial prophylaxis, depending of type of surgical procedure could be grouped as follows: clean, clean-contaminated, neurosurgical, orthopedic, urologic and dirty procedures. Cardiothoracic and vascular could be placed among clean procedures (table 2). Clean-contaminated procedures are head and neck, major head and neck surgical cases in which mouth or pharynx is entered, cholecystectomy, upper gastroduodenal, colorectal, appendectomy, hysterectomy (vaginal, abdominal, radical) "cesarean section" (table1). Neurosurgery procedures in this group are craniotomy and cerebrospinal fluid shunt (table 3). Among orthopedic procedures where antimicrobial prophylaxis is mandatory are: total joint replacement, hip fracture repair as well as other clean orthopedic procedures (table 3). Among urological procedures with antimicrobial prophylaxis one of the most important is transurethral prostatic resection -TURP (table 3). Dirty procedures are those with ruptured abdominal organs and surgery in traumatology (12) (table 2).

 

Table 2.  Antimicrobial prophylaxis of clean and dirty surgical procedures

 

TYPE OF SURGERY	LIKELY PATHOGENS	RECOMMENDED ANTIMICROBIAL REGIMEN	COMMENTS
Clean
Cardiothoracic	Staphylococcus epidermidis, Staph aureus, Corynebacterium, enteric gram-negative bacilli.	Cefuroxime 1.5 gm Add vancomycin 1 gm preop ( single dose) if prosthetic valve or prosthetic vascular graft is being implanted .	Advent of CABG and resultant increased cardiothoracic procedures has shifted the organism spectrum to include gram negative pathogens
Vascular	Staph. aureus (predominant), also gram negative bacilli, coagulase-negative staphylococci and enterococci.		For penicillin allergic patients. If surgery involves the placement of a prosthetic device      ( Staphylococcus epidermidis becomes the problem organism) then give 1 gm IV 1h  preop.
Dirty
Ruptured viscus	Enteric gram negative bacilli, anaerobes ( Bacteroides fragilis) and enterococci.	Ampicillin 1-2 gm Q6H and Gentamicin 3-5 mg/kg divided dose Q12H and Metronidazole 500 mg Q8H (5-7 days). Vancomycin2 replaces ampicillin in penicillin sensitive patients 15 mg/kg or 1 gm IV
Traumatic wound	Staph aureus Group A streptococci, clostridia	Cefazolin 1 gm IV Q8H or cefuroxime 1.5 gm Q12H	Organisms may vary depending on source of injury. If wound has been massively contaminated by soil, manure or dirty water, a regimen with activity against P. aeruginosa, S. aureus, and other gram-negative bacilli is recommended.

 

 

Prophylaxis is recommended in abdominal surgery when surgery involves esophagus, stomach, intestines, biliary tract, large intestine and appendix. The high-risk procedures include operations for cancer, gastric ulcer, bleeding, obstruction (including pyloric stenosis) and perforation as well as surgery involving patients who have received effective acid reducing therapy, either medical (H₂ blockers, proton pump inhibitors) or surgical (1,2). Elective surgery for duodenal ulcer disease has low endogenous bacterial density due to highly acidic environment and thus, the rate of postoperative infection is low. Antimicrobial prophylaxis is beneficial in operations entailing entry of the gastrointestinal tract, with consequent exposure of the surgical wound to endogenous intestinal bacteria. The biliary tract is normally sterile, with only low rate of colonization when elective operations for stone-related disease are undertaken in young patients accordingly, antimicrobial prophylaxis in biliary surgery has been recommended only for high-risk patients defined as those who are over 60 years old or who have had common duct stones, bile duct obstruction, recent acute cholecystitis or prior operation on the biliary tract. (1, 2). Prophylaxis is desirable even in "minimally invasive" surgery such as laparoscopic cholecystectomy and laparoscopic assisted bowel resection. For elective surgical procedures on the colon, rates of infection are high when antimicrobial prophylaxis is not used. In most surgical procedures antimicrobial prophylaxis should be parenteral, and in colon procedures both oral and parenteral. The most common practice in the United States is oral antibiotic administration along with mechanical bowel cleansing the evening before the operation and parenteral antibiotic administration in the operating room just before the incision. (3, 4). Selective gastrointestinal decontamination may be used too. Intestinal tract is the place with largest bacterial colonization in organism. Selective decontamination reduces number of potentially pathogenic bacteria - gram-negative aerobic bacteria and fungi, favoring predomination of anaerobic microorganism. Most common gastrointestinal infections are caused by gram-negative bacteria. They could be the cause of severe infection and sepsis with endotoxemia, further activating immune system leading to systemic inflammatory response and septic shock. Anaerobic bacteria are rarely a cause of infection limiting the spread of colonization of other bacteria and fungi. (11).

Clean urologic procedures encompass urinary tract surgery that do not involve urinary tract entry, with sterile urine. Sterilization of urine is preferable before beginning of elective procedure on the genitourinary tract. If urine is infected, antimicrobial therapy targeting the responsible pathogens isolated in culture samples, should be initiated before the procedure, and continued until the urinary tract infection is resolved (2). Antimicrobial prophylaxis of TURP is still controversial. Urological procedures that involve the intestinal tract are covered by the guidelines listed for general surgical procedures. Like hysterectomies, gynecological procedures entailing entry of the vagina probably all merit prophylaxis.

Other surgical procedures that do not require entry into the gastrointestinal tract, but are associated with high rate of infection (eg. lower extremity vascular procedures, hysterectomy and primary cesarean section), with devastating consequences of infection (eg joint replacement or other prosthetic hardware placement, cardiac procedures, and aortic vascular grafting) or with both (craniotomy) have been widely accepted as indications for antimicrobial prophylaxis. (1). In so called "clean" low risk procedures such as hernia repair, breast operations and skin surgery, antibiotics are given only in a setting of increased probability of postoperative wound infection. Prophylaxis is recommended also in head and neck surgery with entry to oropharynx as well as in newborns. Broad spectrum antibiotics are treatment of choice in children under 30 days old.

 

 

Increased risk of postoperative wound infection is particular in patients with weight loss over 10 %, accompanied with two or more organ system failures, in patients with hypoproteinemia and compromised immunity, extremely obese and diabetics. Increase of postoperative wound infection risk is in proportion with the duration of surgical procedure (10).

 

Antimicrobial prophylaxis - decision, schedule, dosage and duration

 

Chosen agent should be effective against the pathogens most often recovered from infections occurring after that specific procedure and against the endogenous flora of the region of the body being operated upon. Operations involving distal ileum, colon or appendix require the use of an agent or combination of agents with activity against normal endogenous enteral flora such is Enterococcus and large number of enteric anaerobic microorganism such as B. fragilis soy (2, 5). Regimens active against Enterococci are ampicillin, amoxicillin or vancomycin combined with gentamycin. are recommended for prophylaxis of endocarditic when a patient undergoes genitourinary or gastrointestinal tract procedures. Infections developed after gynecological operations (hysterectomy) are usually caused by aerobic bacteria with decreased effectiveness of antibiotics targeting anaerobic bacteria proved no benefit in comparison to cefazolin (6). It is established that cefotetan or cefoxitin should be used for operations involving distal ileum, colon and appendix while cefazolin should be used in all other cases (1).  New generation drugs have still not proved their benefit over cefazolin, cefoxitin and cefotetan in prophylaxis. Vancomycin might be given instead of cefazolin in patient allergic to cephalosporins as well as in conditions with the presence of methicillin resistant Staphylococcus aurous at site of infection (MRSA).  Since vancomycin provides no activity against facultative gram-negative bacilli, which may be involved in settings such as upper gastrointestinal surgery or hysterectomy, another agent with gram -negative activity should be added to regimen under these circumstances. If allergy to cephalosporins is the concern, aztreonam or an aminoglycoside can be administrated with clindamycin. An aminoglycoside can be combined with either clindamycin or metronidazole. Aztreonam should not be used in a two-drug combination with metronidazole because this combination lacks activity against gram-positive cocci and may permit a higher rate of infection caused by Staphylococcus aurous. If this combination is used an agent with activity against gram-positive cocci must be included as well.

The goal in prophylaxis is to achieve inhibitory antimicrobial levels before incision and to maintain adequate levels for the duration of the procedure. It is considered that success of antimicrobial prophylaxis greatly depends on timing of drug administration, with pharmacokinetic data indicating the desirability of administration as close to the time of incision. Having in mind differences in tissue distribution of antibiotics resulting from pharmacokinetic features of specific drug, some medications might be given before entering the operation hall while other could be given at anesthesia induction. Agents used for preoperative parenteral prophylaxis should be administered intravenously during the interval beginning 60 minutes before incision, at anesthesia induction (7). If a drug with shorter half-life is given 120 minutes before incision, its levels may be very low during most of the procedure. For cesarean section, antimicrobial prophylaxis should be delayed until umbilical cord is clamped and than should be initiated immediately. Postoperative initiation is still most popular in practice (8), but is not recommended nor is the administration of the first dose after incision desirable (caesarian section as exception)

The optimal duration of perioperative antimicrobial prophylaxis is not known. Antimicrobial prophylaxis should last 12-24 hours. It should be discontinued 24 hours after finishing the "clean" procedures. Prophylaxis in colorectal surgery should last from 24 -48 hours. Long lasting prophylaxis longer than 48 hours (sometimes over two weeks) is useful only for peripheral vein surgery and cardio-surgical procedures of patients with proven endocarditic that increases the risks of postoperative wound infection (9).

The prophylactic dose should never be smaller than standard therapeutic dose that is in adults for cefazolin, cefoxitin and cefotetan 1-2 gr, and 30-40 mg/kg for children. Many studies stated that single dose was enough, with occasional reports advocating addition of two more administrations. Additional intra-operative doses of an antimicrobial agent should be given at intervals of one or two times the half-life of the drug so the adequate levels are maintained throughout the operation. Long lasting antibiotic administration for prophylactic purposes is both expensive and harmful, favoring appearance of resistant microorganisms (especially if it is given longer than 48 hours). Tree antibiotic doses administrated in timely intervals are considered adequate for prophylaxis of the largest number of surgical procedures. A single dose is adequate for smaller and shorter procedures.

Antimicrobial prophylaxis of surgical procedures is widely accepted method for prevention and minimizing the incidence of postoperative infection. Further achievements should try to adjust prophylactic regimen to bacteriological environment, type of surgical procedure, as well as to patient’ condition and his immunological competence.

 

 

LITERATURE:

 

1.      Page CP, Bohnen JMA, Fletcher JR. Antimicrobial Prophylaxis for Surgical Wounds: guidelines for clinical care. Arch Surg 1993;128: 79-88.

2.      ASHP Commission on Therapeutics. ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery. Clin Pharm 1992; 11: 483-513.

3.      Gorbach SL: Antimicrobial prophylaxis for appendectomy and colorectal surgery. Rev Infect Dis 1991; 13(suppl 110): S815-20.

4.      Solla JA, Rothenberger DA. Preoperative bowel preparation: a survey of colon and rectal surgeons. Dis Colon Rectum 1990; 33: 154-9.

5.      Dellinger EP, Gross PA, Barrett TL, Krause PJ, Martone WJ, McGowan JE, Sweet RL, Wenzel RP. Quality Standard for Antimicrobial Prophylaxis in Surgical Procedures. Clin Infect Dis 1994; 18: 422-7.

6.      HemsellDL: Prophylactic antibiotics in gynecologic and obstetric surgery. Rev Infect Dis 1991; 13(supp110): S821-41.

7.       Galandiuk S, Polk HC, Jagelman DG, Fazio VW. Re-emphasis of priorities in surgical antibiotic prophylaxis. Surg Gynecol Obstet 1989; 169:219-22.

8.      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.

9.      Bencini PL, Galimherti M, Signorini M, Crosti C. Antibiotic prophylaxis of wound infections in skin surgery. Arch Dermatol 1991; 127: 1357-60.

10.    Windsor JA, Hill GL. Protein depletion and surgical risk. Aust NZJ Surg 1988; 58: 711-5.

11.    Ramsay G. The role of selective decontamination of digestive tract. In: Taylor E.(Ed) Infection in surgical practice. Oxford University Press, London, 1991.

12.     Antimicrobial Use Guidelines. Eighth Edition. Ssurgical prophylaxis. University of Wisconsin Hospital, 1996.