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Antimicrobial therapy for surgical patients
Billie Fernsebner, RN
Antimicrobial therapy for surgical patients
“But the rotten stuffe like meale, which is gathered out of old wood, and stocks of trees, being layd upon them, doth cleanse ulcers and bring them to cicatrix.”l
The ancient Greek physician Dioscorides was describing the state of the a r t of antimicrobial therapy as i t existed close to 2,000 years ago. There was no concern for concentration and appropriate dose, no peak and trough blood levels drawn, and no need to ob-
Billie Fernsebner, R N , MSN, CNOR, is a surgical clinical specialist at Mount Auburn Hospital, Cambridge, Mass. A diploma graduate of Newton-Wellesley Hospital School of Nursing, Newton, Mass, she received a BSN from the Union for Experimenting Colleges and Universities,Yellow Springs,Ohio, and an MSN from Boston University. This article won first place in the Applied Fiberoptics writer’s contest. The annual contest is open to AORN members for manuscriptswritten on any aspect of operating room
nursing.
serve for allergic reactions, for antidotes were unknown. Simply take the rotten wood, apply it to an open sore, and let one organism kill another. Today, antimicrobial therapy is no longer a province of folk medicine, but a precise discipline that has been structured by pharmacists and chemists. It is not enough that specific drugs are prescribed to combat specific organisms; these drugs must also be given at specific times for a specific duration. Just as more virulent organisms (resistant to the old antimicrobials) have survived in the hospital setting, so, too, have more potent antimicrobials emerged from the pharmacist’s flasks. These carry not only more killing power, but also more risks and side effects for the patient. To deliver safe, competent care, the operating room nurse must know which antimicrobial is prescribed for which organisms, what adverse reactions may occur, the proper dosage and duration of therapy, and potential drug interactions. She must also be knowledgeable of an antimicrobial’s heritage, as chemists have altered the structure of many to produce synthetic second- and third-generation drugs with strange sounding names. This article will present specific aspects of antimicrobial therapy, including several commonly prescribed categories of antimicrobials, their mechanisms of action, and implications for
AORN Journal, September 1982, Vol36, NO 3
479
nursing care. The advent of modern antimicrobial therapy came in 1938 with Florey's therapeutic evaluation of penicillin. The appearance since then of many effective antimicrobial agents has completely altered medical practice. By the strictest definition, an antimicrobial is a living organism that destroys or inhibits growth of other organisms, but the definition has been expanded to include the many new synthetic and semisynthetic compounds. The goal of all antimicrobial therapy is to destroy or suppress the growth of infecting microorganisms so host defense mechanisms can gain control. Most bacteria, many fungi, and a few viruses and parasites can be controlled with antimicrobials. Mechanisms of action.Antimicrobials are classified into four groups according to what aspect of the bacterium they affect: the cell wall, the cell membrane, the process of protein synthesis a t the ribosome, or the process of nucleic acid synthesis (see Table 1). The drugs are, by definition, chemicals that poison operations of the living cell. Were it not for their selective toxicity, they would kill both pathogen and patient. Some antimicrobials affect structures found only in bacteria, such as the cell wall, while others attack structures that are found in both man and bacteria but are chemically dissimilar, such as the ribosome. Drugs that attack chemically similar structures such as the cell membrane often produce many side effects. Drugs whose action interferes with the cell wall must be used while the cells are actively growing and multiplying. They cannot act on already synthesized cell walls. When the cell wall is broken down, water moves into the cell, causing it to swell and ultimately burste2 Drugs that alter the permeability of the cell membrane cause a leakage of important chemicals in both directions
480
Table 7
Antimicrobial agent mechanisms of action Inhibit cell wall synthesis penicillins cephalosporins vancomycin bacitracin cycloserine Alter cell membrane permeability amphotericin B nystatin polymixin B colistin Inhibit protein synthesis chloramphenicol tetracycline erythromycin aminogylcoside antibiotics rifampin Inhibit nucleic acid synthesis nalidixic acid griseofulvin novobiocin From Betty S Bergersen, Pharmacologyin Nursing, 14th ed (St Louis: C V Mosby, 1979) 475; Lucille Arking, Louis Saravolatz, "Antimicrobial treatment," Nursing Clinics of North America 15 (December 1980) 692.
and eventual cell lysis. Because human cell membranes are similar t o those of bacterial cells, toxicity may occur in areas of the body where the antimicrobial concentrates.3 Drugs that inhibit protein synthesis at the ribosome interfere with the messenger RNA by binding to a specific receptor protein. This results in abnormal protein synthesis and cell death. Drugs that inhibit the process of nucleic acid synthesis do so by interrupting the transmission of genetic information so the cell cannot repli~ate.~
AORN Journal, September 1982, Vol36, No 3
Table 2
Commonly used penicillins Resistant Drug
to penicillinase
Penicillin G Penicillin V
no no
Methicillin Oxacillin Cloxacillin
Yes Yes Yes
Dicloxacillin
Yes
Comments Highly effective against gram-positivebacteria Use only for penicillinase-producing staphylococci Available only for oral use More active against penicillinase-producing S aureus than oxacillin or cloxacillin Effective against staphylococci, pneumococci, group A beta-hemolytic streptococci More active than methicillin Like penicillin G but more active against gram-negative;broad spectrum Produces higher blood level of antibiotic than am piciflin Used synergistically with aminoglycoside
Nafcillin
Ampicillin
no
Amoxicillin
no
Carbenicillin
no
From Betty S Bergersen, Pharmacology in Nursing, 14th ed (St Louis: C V Mosby, 1979) 495. ~~~
~
Categories of antimicrobials Penicillins. The first agent to earn the name “miracle drug” was penicillin, and the name is still well deserved. The only natural penicillin now in common use is penicillin G, the others are synthetics or semisynthetic derivatives. As miraculous as the penicillins are, they have several disadvantages. One is that many are rendered inactive by penicillinase, an enzyme secreted by certain bacteria, most notably, Staphylococcus aureus. Several synthetic penicillins have been produced that are resistant to penicillinase. Table 2 identifies the most commonly used pencillins and indicates those resistant to penicillinase. A second disadvantage is a relatively high incidence of allergic reactions, ranging from contact dermatitis to anaphylaxis. Among the antimi-
crobials, the penicillins are most often responsible for anaphylaxis. It is generally accepted that a person who is sensitive to penicillin should be considered sensitive to all the derivative^.^ Cephalosporins. These are similar to penicillin in chemical structure and are effective against a similar bacterial spectrum. They are resistant to penicillinase and thus can be used against S aureus. Persons sensitive to the penicillins should be considered sensitive to the cephalosporins, as there is a crosssensitivity risk. Among the commonly prescribed cephalosporins are cephalothin sodium and cefazolin sodium from the “first generation.” Second generation cephalosporins are drugs that have been chemically designed to have antibacterial spectra different from the original drugs.
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W
idespread use has resulted in some resistant strains.
Second generation drugs commonly prescribed are cefamandole nafate and cefoxitin sodium. The first of the third generation cephalosporins, cefotaxime sodium, was approved for use in the fall of 198L6 This was followed quickly by the approval of moxalactam. Moxalactam was developed by chemists using the basic structure of the cephalosporins with the sulfur removed and an oxygen atom added. They then linked parts of two penicillins and a cephalosporin to form a new antimicrobial molecule with properties different from those of its ancestors. Although these drugs are expensive and not yet in wide use, they are expected t o be effective against organisms that have previously been sensitive only t o t h e toxic aminoglycosides.7 Aminoglycosides. These antimicrobials are among the most widely used in hospitals today.8 They comprise a group of drugs sharing chemical, antimicrobial, pharmacologic, and toxic characteristics. Used to treat infections caused by gram-negative organisms, these toxic drugs are often held in abeyance until needed by patients with life-threatening infections (many times nosocomial) that may lead to bacteremia and septic shock. They are active against Proteus, Pseudomonas, and Klebsiella species; Serratia marcescens; and Escherichia coli. The three drugs now in use are gentamicin, tobramycin, 482
and amikacin. All the aminoglycosides have doserelated toxic effects and are nephrotoxic and ototoxic. Gentamicin and tobramycin appear to be somewhat less nephrotoxic than amikacin, which is reserved for organisms resistant to tobramycin and gentamicin. The widespread use of aminoglycosides has resulted in some resistant strains of bacteria, which can be a problem because cross-resistance will develop to structurally similar drugs. Thus, organisms resistant to tobramycin will also be resistant to g e n t a m i ~ i n . ~ The aminoglycosides act upon the bacterial ribosome to induce misreading of the genetic code and ultimate cell death. For this reason, they may be used with other antimicrobials to achieve a synergistic effect. For example, one of the penicillins (commonly carbenicillin or ticarcillin) is used t o inhibit cell wall synthesis, providing easier access to the cell nucleus by the aminoglycoside. Drug combinations commonly used are carbenicillin and gentamicin against Pseudomonas organisms, a cephalosporin and gentamicin against Klebsiella organisms, and a penicillin and gentamicin against S uiridans or enterococci. Prophylaxis Perioperative antimicrobial prophylaxis appears most warranted when: (1)the incidence and consequences of infection
AORN Journal, September 1982, Vol36, N o 3
are great, (2) the offending organisms are predictable and susceptible to antimicrobials, and (3) the period of exposure to possible infection is brief. When these criteria are met, timing is still the most critical factor in prophylaxis, as the period when therapy will be effective is extremely narrow. The physiological response to contamination is inflammation with small vessels leaking plasma. About two hours later, leukocytes emerge from the vessels and begin phagocytosis. This exudative phase parallels the “decisive period” in infection. During this period, if the combination of phagocytosis and antimicrobials kills the invading organisms, the patient will escape serious wound infection and tissue damage. It is only in this period that antimicrobials effectively prevent wound suppuration. If given later, they will have no prophylactic effect.1° Thus, the term prophylactic therapy applies t o administration of drugs shortly before, during, or shortly after bacterial contamination. Significant tissue concentration of antimicrobials must be attained during the decisive period. If given several hours later, this constitutes early treatment, which follows different guiding principles. Studies have shown that adequate tissue levels during the decisive period can be obtained by a single dose administered shortly before surgery. With the exception of prolonged surgery, additional doses earlier or later are unnecessary, for once a wound is closed, significant contamination ceases.” In clean surgery, there is little need for prophylaxis, because the cost and risk exceed the benefits. Exceptions are procedures in which prostheses such as heart valves, joints, or vascular grafts are inserted, for while the risk of infection may be low, the consequences of infection are great. Knowing the usual pathogens har-
bored at surgical sites guides the physician in choosing a n antibiotic for prophylaxis. Other considerations include the antimicrobial’s cost and toxicity. The cephalosporins are frequently used because of their low toxicity and broad spectrum of effectiveness. Most a r e equally effective, although low doses of cefazolin produce high serum levels and a prolonged half-life. It is relatively painless when given intramuscularly and is less expensive than others. Depending on the drug ordered and the surgery scheduled, most prophylactic antimicrobials can be administered intramuscularly on call to the operating room or intravenously with anesthesia induction. Table 3 lists antimicrobials recommended for prophylaxis. Nursing implications. It is important for the OR nurse to know how a prophylactic antimicrobial is to be administered. If it is ordered IV “on call” to the operating room and there is an unanticipated delay in the schedule, the antimicrobial may reach its peak level while the patient is in the holding area. A patient who requires a lengthy preparation prior to the actual surgery may also not be getting the peak effect at the right time. To assure peak levels during the decisive period, antimicrobials should be given IV with anesthesia induction. This requires, however, that the nurse be observant for allergic reactions at a time when she is already busy with the many functions related to the start of surgery. In addition t o prophylaxis, antimicrobials may be given to the surgical patient for treatment. The OR nurse may be the person responsible for giving the next dose of a drug for treatment of an infection, or she may be responsible for administering the first dose to a patient with multiple trauma o r ruptured viscus. The goal of the therapy is to provide adequate and safe tissue levels
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183
Table 3
Antimicrobials for prophylaxis Clean surgery
neomycin and erythromycin (1gm of each, orally three times a day) 0 cefoxitin (1 gm IV) or clindamycin (600 mg 0
heart valve 0 penicillinase-resistant penicillin (1 gm IV) 0 cephalosporin (1 gm IM/IV) 0 vancomycin (1 gm IV) bypass graft 0 cephalosporin (1 gm IM/IV) joint replacement penicillinase-resistant penicillin (1 gm IV) 0 cephalosporin (1 gm IM/IV) internal fixation of femur 0 penicillin (1 gm IV) 0 cephalosporin (1 gm IM/IV) 0 vancomycin (1 gm IV) Clean contaminated surgery
head and neck entering oral cavity or pharynx 0 cephalosporin (1 gm IM/IV) 0 aqueous penicillin G (1 million units IV) gastroduodenal (for high-risk patients only) 0 cephalosporin (1 gm IM/IV) biliary tract (for high-risk patients only) 0 cephalosporin (1 gm IM/IV) colorectal
IV) with
gentamicin (1.5 mg/kg IM/IV) or tobramycin (1.5 mg/kg IM/IV) vaginal or abdominal hysterectomy 0 cephalosporin (1 gm IM/IV) cesarean section (for high risk patients only) 0 cephalosporin (1 gm IV after cord is clamped) Dirty surgery
Therapeutic courses of antimicrobials are generally required, as criteria for prophylaxis have not been met. ruptured viscus 0 clindamycin and gentamicin 0 tobramycin 0 cefoxitin traumatic wounds 0 penicillinase-resistant penicillin 0 cephalosporin
From “Antimicrobialprophylaxis,” The Medical Lefter on Drugs and Therapeutics 23 (Sept 4, 1981) 80.
of the antimicrobial. Whether initiating or maintaining the therapy, the nurse has a critical role in avoiding potential drug interactions or toxic reactions. Proper doses Dosages of the penicillins and cephalosporins vary widely and are determined by the sensitivity of the organism, severity of infection, and clinical response. Dosages for children under 12 years of age are based on body weight. An example of the wide variation in dosages may be seen with penicillin G potassium, which may be administered a t 5 million units per day for a streptococcal infection and 20 million units 484
per day for a clostridial infection. Nursing responsibilities include accurate assessment of the patient for a history of penicillin sensitivities and observing for any sensitivity or untoward reaction when the drug is administered for the first time. When oral penicillins are administered they should be given one hour before or after meals, as they are bound to food. It is also recommended they not be given with acid h i t juices. Patients receiving intravenous penicillin therapy should be observed for signs and symptoms of hyperkalemia and hypernatremia, since most penicillins are sodium or potassium salts. (Twenty million units of penicillin
AORN Journal, September 1982, Vol36, No 3
he goal is providing safe tissue levels of the antimicrobial.
T
G potassium contain 32 mEq of potassium.>12 The aminoglycosides have the greatest potential for problems. If doses are administered too early, excessive blood levels and toxicity may occur. Given too late, the patient may have periods with subtherapeutic levels. Loading orprirning dose is the term applied to the dose given when therapy is initiated. It is calculated to achieve a rapid, therapeutic concentration of drug in the serum. The dose is based on the peak level of the drug desired and the patient's weight. Because the aminoglycosides do not distribute into the body fat, ideal body weight should be used for obese patients.13 The termpeak refers to the maximum concentration of the drug in plasma. The aminoglycosides reach their peak level 30 to 60 minutes after a dose is given. The recommended peak for tobramycin and gentamicin is 4 to 8 pg/ml. For amikacin, it is 10 to 30 pg/ml. Peaks higher than recommended may lead to eighth cranial nerve damage. To obtain accurate peak levels, serum must be drawn minutes after completion of an IV dose. Dosages for tobramycin and gentamicin are calculated at 3 to 5 mg/kg/ day for adults, with administration divided into three equal doses. In children, the doses are calculated a t 6 to 7.5 mg/kg/day, and in infants, 7.5 mg/kg/ day. Doses for amikacin are 15 mg/kg/
day for adults, children, and older infants, with administration in two or three equal doses. Newborns should receive 10 mg/kg for a loading dose and then 7.5 mg/kg every 12 hours. Trough levels, which are t h e minimum concentrations of a drug in the serum, are just as critical to monitor as peaks. The recommended trough level is 1to 2 pglml for gentamicin and tobramycin and under 10 pg/ml for amikacin. Troughs greater than the recommended level increase the risk of nephrotoxicity because the drug concentration in the kidney does not fall. Amikacin is considered the most ototoxic and nephrotoxic of the three. With all of the aminoglycosides, the dose is excreted unchanged in the urine. Because of this, they are highly effective in treating serious urinary tract infections.l* When administered intravenously, aminoglycosides are usually diluted in 100 ml of 5% dextrose in water or normal saline. This should be given over a 30 to 40 minute period, as a faster rate can cause transient peak levels higher than recommended. Likewise, too slow a rate will not provide a therapeutic level. The aminoglycosides coprecipitate when mixed with heparin. If the drugs are to be given through a heparin lock, the heparin must be flushed out before each administration. Because they are an acid, aminoglycosides are also in-
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compatible w i t h some o f the cephalosporins and penicillins, which are bases. They should either be given a t separate times or through separate lines. One particular caution i s that neuromuscular blockade leading t o respiratory arrest i s a possible adverse effect when aminoglycosides are used concurr e n t l y w i t h neuromuscular b l o c k i n g agents or anesthetic agents.15 Summary. The operating room nurse plays a critical role in the administrat i o n o f antimicrobial therapy for prophylaxis and for treatment. W h e n aminoglycosides are given, the fine line between a therapeutic and toxic dose presents an additional challenge. Timing i s equally critical in administering a prophylactic dose of a cephalosporin; too early and it w i l l be ineffective and too late, it may necessitate a full course of treatment r a t h e r t h a n t h e one dose. Armed with the proper knowledge and skills, the operating room nurse w i l l be able t o provide the safe competent care that patients receiving antimicrobials should expect. 0 Notes 1. lago Galdston, The lmpact of Antibiotics (New York: International Universities Press, 1958) 19. 2. Lucille Arking, Louis Saravolatz, "Antimicrobial treatment," Nursing Clinics of North America 15 (December 1980) 694-696. 3. Ibid. 4. Ibid, 695-696. 5. Betty S Bergersen, Pharmacology in Nursing, 14th ed (St Louis: C V Mosby, 1979) 482. 6. "New cephalosporin approved as prophylactic," AORN Journal 35 (February 1982) 179. 7. Temple W Williams, Daniel Jackson, "New antibiotics-uses and dangers," Heart & Lung 9 (November-December 1980) 1094. 8. Julie Langslet, Maureen L Habel, "The aminoglycoside antibiotics," American Journal of Nursing 81 (June 1981) 1144. 9. Williams, Jackson, "New antibiotics," 1095. 10. Jay Hirschmann, "Rational antibiotic prophylaxis," Hospital Practice (November 1981) 106. 11. Ibid, 107. 12. Bergersen, Pharmacology in Nursing, 486-
486
487. 13. Langslet, Habel, "The aminoglycoside antibiotics," 1145. 14. Ibid. 15. Bergersen, Pharmacology in Nursing, 494.
No pump failure in diabetic deaths Looking into 11 deaths in 1981 of diabetic patients using insulin infusion pumps, a national panel has found no evidence of pump malfunctionor failure. The patientswere using pumps from more tnan one manufacturer. Although none of the deaths was due to the infusion pumps, the panel suggested some of the deaths may have been due to the intensive glycemia control used as a therapeutic goal, according to a report in the Feb 26 Morbidity and Mortality Weekly Report. About 4,000 pumps are in use among the nation's 250,000 to 750,000 insulin-dependentdiabetics. The device administers insulin subcutaneously at a constant low level and delivers additional amounts before meals. Until more is learned, the panel recommends that physicians and patients exercise prudence in selecting goals of therapy, appropriately monitoring blood-glucoselevels, and regulating insulin dosage. The group included representatives of the National Institutes of Health, the US Food and Drug Administration, the National Diabetes Advisory Board, and other diabetes experts. The panel also decided that a better description is needed of the characteristics of the population using the device along with information about complications encountered by a comparable group of diabetics that does not use the device.
AORN Journal, September 1982, Vol36, N o 3
Antimicrobial therapy for surgical patients
“But the rotten stuffe like meale, which is gathered out of old wood, and stocks of trees, being layd upon them, doth cleanse ulcers and bring them to cicatrix.”l
The ancient Greek physician Dioscorides was describing the state of the a r t of antimicrobial therapy as i t existed close to 2,000 years ago. There was no concern for concentration and appropriate dose, no peak and trough blood levels drawn, and no need to ob-
Billie Fernsebner, R N , MSN, CNOR, is a surgical clinical specialist at Mount Auburn Hospital, Cambridge, Mass. A diploma graduate of Newton-Wellesley Hospital School of Nursing, Newton, Mass, she received a BSN from the Union for Experimenting Colleges and Universities,Yellow Springs,Ohio, and an MSN from Boston University. This article won first place in the Applied Fiberoptics writer’s contest. The annual contest is open to AORN members for manuscriptswritten on any aspect of operating room
nursing.
serve for allergic reactions, for antidotes were unknown. Simply take the rotten wood, apply it to an open sore, and let one organism kill another. Today, antimicrobial therapy is no longer a province of folk medicine, but a precise discipline that has been structured by pharmacists and chemists. It is not enough that specific drugs are prescribed to combat specific organisms; these drugs must also be given at specific times for a specific duration. Just as more virulent organisms (resistant to the old antimicrobials) have survived in the hospital setting, so, too, have more potent antimicrobials emerged from the pharmacist’s flasks. These carry not only more killing power, but also more risks and side effects for the patient. To deliver safe, competent care, the operating room nurse must know which antimicrobial is prescribed for which organisms, what adverse reactions may occur, the proper dosage and duration of therapy, and potential drug interactions. She must also be knowledgeable of an antimicrobial’s heritage, as chemists have altered the structure of many to produce synthetic second- and third-generation drugs with strange sounding names. This article will present specific aspects of antimicrobial therapy, including several commonly prescribed categories of antimicrobials, their mechanisms of action, and implications for
AORN Journal, September 1982, Vol36, NO 3
479
nursing care. The advent of modern antimicrobial therapy came in 1938 with Florey's therapeutic evaluation of penicillin. The appearance since then of many effective antimicrobial agents has completely altered medical practice. By the strictest definition, an antimicrobial is a living organism that destroys or inhibits growth of other organisms, but the definition has been expanded to include the many new synthetic and semisynthetic compounds. The goal of all antimicrobial therapy is to destroy or suppress the growth of infecting microorganisms so host defense mechanisms can gain control. Most bacteria, many fungi, and a few viruses and parasites can be controlled with antimicrobials. Mechanisms of action.Antimicrobials are classified into four groups according to what aspect of the bacterium they affect: the cell wall, the cell membrane, the process of protein synthesis a t the ribosome, or the process of nucleic acid synthesis (see Table 1). The drugs are, by definition, chemicals that poison operations of the living cell. Were it not for their selective toxicity, they would kill both pathogen and patient. Some antimicrobials affect structures found only in bacteria, such as the cell wall, while others attack structures that are found in both man and bacteria but are chemically dissimilar, such as the ribosome. Drugs that attack chemically similar structures such as the cell membrane often produce many side effects. Drugs whose action interferes with the cell wall must be used while the cells are actively growing and multiplying. They cannot act on already synthesized cell walls. When the cell wall is broken down, water moves into the cell, causing it to swell and ultimately burste2 Drugs that alter the permeability of the cell membrane cause a leakage of important chemicals in both directions
480
Table 7
Antimicrobial agent mechanisms of action Inhibit cell wall synthesis penicillins cephalosporins vancomycin bacitracin cycloserine Alter cell membrane permeability amphotericin B nystatin polymixin B colistin Inhibit protein synthesis chloramphenicol tetracycline erythromycin aminogylcoside antibiotics rifampin Inhibit nucleic acid synthesis nalidixic acid griseofulvin novobiocin From Betty S Bergersen, Pharmacologyin Nursing, 14th ed (St Louis: C V Mosby, 1979) 475; Lucille Arking, Louis Saravolatz, "Antimicrobial treatment," Nursing Clinics of North America 15 (December 1980) 692.
and eventual cell lysis. Because human cell membranes are similar t o those of bacterial cells, toxicity may occur in areas of the body where the antimicrobial concentrates.3 Drugs that inhibit protein synthesis at the ribosome interfere with the messenger RNA by binding to a specific receptor protein. This results in abnormal protein synthesis and cell death. Drugs that inhibit the process of nucleic acid synthesis do so by interrupting the transmission of genetic information so the cell cannot repli~ate.~
AORN Journal, September 1982, Vol36, No 3
Table 2
Commonly used penicillins Resistant Drug
to penicillinase
Penicillin G Penicillin V
no no
Methicillin Oxacillin Cloxacillin
Yes Yes Yes
Dicloxacillin
Yes
Comments Highly effective against gram-positivebacteria Use only for penicillinase-producing staphylococci Available only for oral use More active against penicillinase-producing S aureus than oxacillin or cloxacillin Effective against staphylococci, pneumococci, group A beta-hemolytic streptococci More active than methicillin Like penicillin G but more active against gram-negative;broad spectrum Produces higher blood level of antibiotic than am piciflin Used synergistically with aminoglycoside
Nafcillin
Ampicillin
no
Amoxicillin
no
Carbenicillin
no
From Betty S Bergersen, Pharmacology in Nursing, 14th ed (St Louis: C V Mosby, 1979) 495. ~~~
~
Categories of antimicrobials Penicillins. The first agent to earn the name “miracle drug” was penicillin, and the name is still well deserved. The only natural penicillin now in common use is penicillin G, the others are synthetics or semisynthetic derivatives. As miraculous as the penicillins are, they have several disadvantages. One is that many are rendered inactive by penicillinase, an enzyme secreted by certain bacteria, most notably, Staphylococcus aureus. Several synthetic penicillins have been produced that are resistant to penicillinase. Table 2 identifies the most commonly used pencillins and indicates those resistant to penicillinase. A second disadvantage is a relatively high incidence of allergic reactions, ranging from contact dermatitis to anaphylaxis. Among the antimi-
crobials, the penicillins are most often responsible for anaphylaxis. It is generally accepted that a person who is sensitive to penicillin should be considered sensitive to all the derivative^.^ Cephalosporins. These are similar to penicillin in chemical structure and are effective against a similar bacterial spectrum. They are resistant to penicillinase and thus can be used against S aureus. Persons sensitive to the penicillins should be considered sensitive to the cephalosporins, as there is a crosssensitivity risk. Among the commonly prescribed cephalosporins are cephalothin sodium and cefazolin sodium from the “first generation.” Second generation cephalosporins are drugs that have been chemically designed to have antibacterial spectra different from the original drugs.
AORN Journal, September 1982, Vol36, No 3
481
W
idespread use has resulted in some resistant strains.
Second generation drugs commonly prescribed are cefamandole nafate and cefoxitin sodium. The first of the third generation cephalosporins, cefotaxime sodium, was approved for use in the fall of 198L6 This was followed quickly by the approval of moxalactam. Moxalactam was developed by chemists using the basic structure of the cephalosporins with the sulfur removed and an oxygen atom added. They then linked parts of two penicillins and a cephalosporin to form a new antimicrobial molecule with properties different from those of its ancestors. Although these drugs are expensive and not yet in wide use, they are expected t o be effective against organisms that have previously been sensitive only t o t h e toxic aminoglycosides.7 Aminoglycosides. These antimicrobials are among the most widely used in hospitals today.8 They comprise a group of drugs sharing chemical, antimicrobial, pharmacologic, and toxic characteristics. Used to treat infections caused by gram-negative organisms, these toxic drugs are often held in abeyance until needed by patients with life-threatening infections (many times nosocomial) that may lead to bacteremia and septic shock. They are active against Proteus, Pseudomonas, and Klebsiella species; Serratia marcescens; and Escherichia coli. The three drugs now in use are gentamicin, tobramycin, 482
and amikacin. All the aminoglycosides have doserelated toxic effects and are nephrotoxic and ototoxic. Gentamicin and tobramycin appear to be somewhat less nephrotoxic than amikacin, which is reserved for organisms resistant to tobramycin and gentamicin. The widespread use of aminoglycosides has resulted in some resistant strains of bacteria, which can be a problem because cross-resistance will develop to structurally similar drugs. Thus, organisms resistant to tobramycin will also be resistant to g e n t a m i ~ i n . ~ The aminoglycosides act upon the bacterial ribosome to induce misreading of the genetic code and ultimate cell death. For this reason, they may be used with other antimicrobials to achieve a synergistic effect. For example, one of the penicillins (commonly carbenicillin or ticarcillin) is used t o inhibit cell wall synthesis, providing easier access to the cell nucleus by the aminoglycoside. Drug combinations commonly used are carbenicillin and gentamicin against Pseudomonas organisms, a cephalosporin and gentamicin against Klebsiella organisms, and a penicillin and gentamicin against S uiridans or enterococci. Prophylaxis Perioperative antimicrobial prophylaxis appears most warranted when: (1)the incidence and consequences of infection
AORN Journal, September 1982, Vol36, N o 3
are great, (2) the offending organisms are predictable and susceptible to antimicrobials, and (3) the period of exposure to possible infection is brief. When these criteria are met, timing is still the most critical factor in prophylaxis, as the period when therapy will be effective is extremely narrow. The physiological response to contamination is inflammation with small vessels leaking plasma. About two hours later, leukocytes emerge from the vessels and begin phagocytosis. This exudative phase parallels the “decisive period” in infection. During this period, if the combination of phagocytosis and antimicrobials kills the invading organisms, the patient will escape serious wound infection and tissue damage. It is only in this period that antimicrobials effectively prevent wound suppuration. If given later, they will have no prophylactic effect.1° Thus, the term prophylactic therapy applies t o administration of drugs shortly before, during, or shortly after bacterial contamination. Significant tissue concentration of antimicrobials must be attained during the decisive period. If given several hours later, this constitutes early treatment, which follows different guiding principles. Studies have shown that adequate tissue levels during the decisive period can be obtained by a single dose administered shortly before surgery. With the exception of prolonged surgery, additional doses earlier or later are unnecessary, for once a wound is closed, significant contamination ceases.” In clean surgery, there is little need for prophylaxis, because the cost and risk exceed the benefits. Exceptions are procedures in which prostheses such as heart valves, joints, or vascular grafts are inserted, for while the risk of infection may be low, the consequences of infection are great. Knowing the usual pathogens har-
bored at surgical sites guides the physician in choosing a n antibiotic for prophylaxis. Other considerations include the antimicrobial’s cost and toxicity. The cephalosporins are frequently used because of their low toxicity and broad spectrum of effectiveness. Most a r e equally effective, although low doses of cefazolin produce high serum levels and a prolonged half-life. It is relatively painless when given intramuscularly and is less expensive than others. Depending on the drug ordered and the surgery scheduled, most prophylactic antimicrobials can be administered intramuscularly on call to the operating room or intravenously with anesthesia induction. Table 3 lists antimicrobials recommended for prophylaxis. Nursing implications. It is important for the OR nurse to know how a prophylactic antimicrobial is to be administered. If it is ordered IV “on call” to the operating room and there is an unanticipated delay in the schedule, the antimicrobial may reach its peak level while the patient is in the holding area. A patient who requires a lengthy preparation prior to the actual surgery may also not be getting the peak effect at the right time. To assure peak levels during the decisive period, antimicrobials should be given IV with anesthesia induction. This requires, however, that the nurse be observant for allergic reactions at a time when she is already busy with the many functions related to the start of surgery. In addition t o prophylaxis, antimicrobials may be given to the surgical patient for treatment. The OR nurse may be the person responsible for giving the next dose of a drug for treatment of an infection, or she may be responsible for administering the first dose to a patient with multiple trauma o r ruptured viscus. The goal of the therapy is to provide adequate and safe tissue levels
AORN Journal, September 1982, V o l 3 6 , No 3
183
Table 3
Antimicrobials for prophylaxis Clean surgery
neomycin and erythromycin (1gm of each, orally three times a day) 0 cefoxitin (1 gm IV) or clindamycin (600 mg 0
heart valve 0 penicillinase-resistant penicillin (1 gm IV) 0 cephalosporin (1 gm IM/IV) 0 vancomycin (1 gm IV) bypass graft 0 cephalosporin (1 gm IM/IV) joint replacement penicillinase-resistant penicillin (1 gm IV) 0 cephalosporin (1 gm IM/IV) internal fixation of femur 0 penicillin (1 gm IV) 0 cephalosporin (1 gm IM/IV) 0 vancomycin (1 gm IV) Clean contaminated surgery
head and neck entering oral cavity or pharynx 0 cephalosporin (1 gm IM/IV) 0 aqueous penicillin G (1 million units IV) gastroduodenal (for high-risk patients only) 0 cephalosporin (1 gm IM/IV) biliary tract (for high-risk patients only) 0 cephalosporin (1 gm IM/IV) colorectal
IV) with
gentamicin (1.5 mg/kg IM/IV) or tobramycin (1.5 mg/kg IM/IV) vaginal or abdominal hysterectomy 0 cephalosporin (1 gm IM/IV) cesarean section (for high risk patients only) 0 cephalosporin (1 gm IV after cord is clamped) Dirty surgery
Therapeutic courses of antimicrobials are generally required, as criteria for prophylaxis have not been met. ruptured viscus 0 clindamycin and gentamicin 0 tobramycin 0 cefoxitin traumatic wounds 0 penicillinase-resistant penicillin 0 cephalosporin
From “Antimicrobialprophylaxis,” The Medical Lefter on Drugs and Therapeutics 23 (Sept 4, 1981) 80.
of the antimicrobial. Whether initiating or maintaining the therapy, the nurse has a critical role in avoiding potential drug interactions or toxic reactions. Proper doses Dosages of the penicillins and cephalosporins vary widely and are determined by the sensitivity of the organism, severity of infection, and clinical response. Dosages for children under 12 years of age are based on body weight. An example of the wide variation in dosages may be seen with penicillin G potassium, which may be administered a t 5 million units per day for a streptococcal infection and 20 million units 484
per day for a clostridial infection. Nursing responsibilities include accurate assessment of the patient for a history of penicillin sensitivities and observing for any sensitivity or untoward reaction when the drug is administered for the first time. When oral penicillins are administered they should be given one hour before or after meals, as they are bound to food. It is also recommended they not be given with acid h i t juices. Patients receiving intravenous penicillin therapy should be observed for signs and symptoms of hyperkalemia and hypernatremia, since most penicillins are sodium or potassium salts. (Twenty million units of penicillin
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he goal is providing safe tissue levels of the antimicrobial.
T
G potassium contain 32 mEq of potassium.>12 The aminoglycosides have the greatest potential for problems. If doses are administered too early, excessive blood levels and toxicity may occur. Given too late, the patient may have periods with subtherapeutic levels. Loading orprirning dose is the term applied to the dose given when therapy is initiated. It is calculated to achieve a rapid, therapeutic concentration of drug in the serum. The dose is based on the peak level of the drug desired and the patient's weight. Because the aminoglycosides do not distribute into the body fat, ideal body weight should be used for obese patients.13 The termpeak refers to the maximum concentration of the drug in plasma. The aminoglycosides reach their peak level 30 to 60 minutes after a dose is given. The recommended peak for tobramycin and gentamicin is 4 to 8 pg/ml. For amikacin, it is 10 to 30 pg/ml. Peaks higher than recommended may lead to eighth cranial nerve damage. To obtain accurate peak levels, serum must be drawn minutes after completion of an IV dose. Dosages for tobramycin and gentamicin are calculated at 3 to 5 mg/kg/ day for adults, with administration divided into three equal doses. In children, the doses are calculated a t 6 to 7.5 mg/kg/day, and in infants, 7.5 mg/kg/ day. Doses for amikacin are 15 mg/kg/
day for adults, children, and older infants, with administration in two or three equal doses. Newborns should receive 10 mg/kg for a loading dose and then 7.5 mg/kg every 12 hours. Trough levels, which are t h e minimum concentrations of a drug in the serum, are just as critical to monitor as peaks. The recommended trough level is 1to 2 pglml for gentamicin and tobramycin and under 10 pg/ml for amikacin. Troughs greater than the recommended level increase the risk of nephrotoxicity because the drug concentration in the kidney does not fall. Amikacin is considered the most ototoxic and nephrotoxic of the three. With all of the aminoglycosides, the dose is excreted unchanged in the urine. Because of this, they are highly effective in treating serious urinary tract infections.l* When administered intravenously, aminoglycosides are usually diluted in 100 ml of 5% dextrose in water or normal saline. This should be given over a 30 to 40 minute period, as a faster rate can cause transient peak levels higher than recommended. Likewise, too slow a rate will not provide a therapeutic level. The aminoglycosides coprecipitate when mixed with heparin. If the drugs are to be given through a heparin lock, the heparin must be flushed out before each administration. Because they are an acid, aminoglycosides are also in-
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compatible w i t h some o f the cephalosporins and penicillins, which are bases. They should either be given a t separate times or through separate lines. One particular caution i s that neuromuscular blockade leading t o respiratory arrest i s a possible adverse effect when aminoglycosides are used concurr e n t l y w i t h neuromuscular b l o c k i n g agents or anesthetic agents.15 Summary. The operating room nurse plays a critical role in the administrat i o n o f antimicrobial therapy for prophylaxis and for treatment. W h e n aminoglycosides are given, the fine line between a therapeutic and toxic dose presents an additional challenge. Timing i s equally critical in administering a prophylactic dose of a cephalosporin; too early and it w i l l be ineffective and too late, it may necessitate a full course of treatment r a t h e r t h a n t h e one dose. Armed with the proper knowledge and skills, the operating room nurse w i l l be able t o provide the safe competent care that patients receiving antimicrobials should expect. 0 Notes 1. lago Galdston, The lmpact of Antibiotics (New York: International Universities Press, 1958) 19. 2. Lucille Arking, Louis Saravolatz, "Antimicrobial treatment," Nursing Clinics of North America 15 (December 1980) 694-696. 3. Ibid. 4. Ibid, 695-696. 5. Betty S Bergersen, Pharmacology in Nursing, 14th ed (St Louis: C V Mosby, 1979) 482. 6. "New cephalosporin approved as prophylactic," AORN Journal 35 (February 1982) 179. 7. Temple W Williams, Daniel Jackson, "New antibiotics-uses and dangers," Heart & Lung 9 (November-December 1980) 1094. 8. Julie Langslet, Maureen L Habel, "The aminoglycoside antibiotics," American Journal of Nursing 81 (June 1981) 1144. 9. Williams, Jackson, "New antibiotics," 1095. 10. Jay Hirschmann, "Rational antibiotic prophylaxis," Hospital Practice (November 1981) 106. 11. Ibid, 107. 12. Bergersen, Pharmacology in Nursing, 486-
486
487. 13. Langslet, Habel, "The aminoglycoside antibiotics," 1145. 14. Ibid. 15. Bergersen, Pharmacology in Nursing, 494.
No pump failure in diabetic deaths Looking into 11 deaths in 1981 of diabetic patients using insulin infusion pumps, a national panel has found no evidence of pump malfunctionor failure. The patientswere using pumps from more tnan one manufacturer. Although none of the deaths was due to the infusion pumps, the panel suggested some of the deaths may have been due to the intensive glycemia control used as a therapeutic goal, according to a report in the Feb 26 Morbidity and Mortality Weekly Report. About 4,000 pumps are in use among the nation's 250,000 to 750,000 insulin-dependentdiabetics. The device administers insulin subcutaneously at a constant low level and delivers additional amounts before meals. Until more is learned, the panel recommends that physicians and patients exercise prudence in selecting goals of therapy, appropriately monitoring blood-glucoselevels, and regulating insulin dosage. The group included representatives of the National Institutes of Health, the US Food and Drug Administration, the National Diabetes Advisory Board, and other diabetes experts. The panel also decided that a better description is needed of the characteristics of the population using the device along with information about complications encountered by a comparable group of diabetics that does not use the device.
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