Feb 7, 2009
Penicillins belong to the b-lactam family of antibiotics, so named because of the b-lactam molecular ring in their chemical composition. Because of the differing uses, it is instructive to consider them by categories.
Penicillins G and V are highly active against Streptococcus pyogenes (b-hemolytic group A), Streptococcus pneumoniae (most strains), actinomycosis, and a dwindling proportion of oral anaerobic organisms. They are inactivated by penicillinase produced by Staphylococcus aureus and other enzymes produced by a variety of gram-negative organisms, such as Haemophilus influenzae, Moraxella catarrhalis, and oral anaerobic organisms. These enzymes are collectively called b-lactamases, and they render many of the penicillin and cephalosporin agents inactive. Through a different mechanism, related to protein binding rather than enzymes, S. pneumoniae is becoming increasingly resistant to the penicillins and cephalosporins. Intermediate-level resistance may yet allow effective treatment with high doses of amoxicillin or second- and third-generation cephalosporins, but highly or multiply resistant strains are resistant to all penicillins, most cephalosporins, macrolides, tetracyclines, clindamycin, and chloramphenicol. Because gastric acid exerts an adverse effect on penicillins G and V, they are best administered on an empty stomach (1 hour before a meal).
Rashes occur among 5% of persons who take penicillin. They do not entirely preclude future use of penicillin because rashes recur among only 50% of these patients. When they are retreated with penicillin, these patients usually need little more than antihistamine treatment. Anaphylaxis is a different reaction, and it does not necessarily occur among patients with previous rash reactions. Because it is life threatening, anaphylaxis is considered a lifelong contraindication to future use of penicillin. All penicillins carry the same risk of causing anaphylaxis.
Antistaphylococcal penicillins resist penicillinase. Methicillin, oxacillin, cloxacillin, dicloxacillin, and nafcillin are agents in this category. Dicloxacillin attains the highest blood levels of any of the orally administered antistaphylococcal penicillins. Nafcillin is preferred for intravenous use, especially to treat patients with renal impairment, because it can be excreted through the liver. These agents are highly effective against Staph. aureus, even penicillin-resistant strains, except for a troublesome newcomer called methicillin-resistant staphylococcus, the prevalence of which reaches 10% of the staphylococcal strains in some hospitals. This organism is resistant to all penicillins and all cephalosporins. Except for methicillin, antistaphylococcal penicillins are active against streptococcal and most pneumococcal infections.
Aminopenicillins, such as ampicillin and amoxicillin, extend the activity spectrum to gram-negative organisms such as Proteus organisms, Escherichia coli, and H. influenzae, but Staph. aureus is resistant to drugs in this category. Furthermore, b-lactamase enzymes produced by 20% to 30% of H. influenzae strains and most strains of M. catarrhalis cause resistance to these agents. Aminopenicillins produce rashes more commonly than do other penicillins, especially if the patient has infectious mononucleosis (50% incidence of rash). Amoxicillin attains higher levels in the serum and middle ear fluid than does ampicillin, and it is well absorbed orally at meal times.
Augmented penicillins are those in which the penicillin is combined with an agent that inactivates resistance-producing b-lactamase enzymes. For the management of infection by staphylococci, H. influenzae, M. catarrhalis, anaerobic organisms, and others, amoxicillin is combined with potassium clavulanate (Augmentin, oral), and ampicillin is combined with sulbactam (Unasyn, parenteral). For the management of Pseudomonas aeruginosa infection and a broad spectrum of other infections, ticarcillin is combined with potassium clavulanate (Timentin, parenteral).
Antipseudomonal penicillins are active against most gram-negative bacteria but not gram-positive organisms, such as Staph. aureus. The activity of these agents against P. aeruginosa separates them from most other antibiotics. They are administered parenterally. Ticarcillin is more active than is carbenicillin. Piperacillin is the most active of all drugs in this category. In the management of serious pseudomonal infection, these drugs often are used in combination with an aminoglycoside, such as gentamicin, for a synergistic effect.
Cephalosporins also belong to the b-lactam family of drugs. This chemical relation probably means that patients with a history of penicillin anaphylaxis should avoid cephalosporins; however, cephalosporins are commonly and safely used by patients with a history of penicillin rashes. These drugs are categorized into first, second, and third generations. In general, first-generation agents are most active against gram-positive bacteria, and third-generation agents are highly active against gram-negative bacteria. Second-generation agents occupy an intermediate position. It is easiest to be familiar with one oral agent and one or two parenteral agents in each generation. For information about other agents, see the Pocket Guide to Antimicrobial Therapy (2).
First-generation oral cephalexin (Keflex) is highly effective against gram-positive organisms such as streptococci, pneumococci except for penicillin-resistant strains, and staphylococci except the methicillin-resistant strains. It is also active against a few gram-negative bacteria, but Staph. aureus is the organism against which it is most commonly used. For parenteral use, cefazolin (Ancef, Kefzol) produces the longest duration of action of the first-generation agents. Its antistaphylococcal activity is widely used in prophylaxis against surgical infections after operations in which a skin incision is made.
Second-generation cefuroxime is available for both parenteral (Zinacef) and oral (Ceftin) use. Both are highly active against gram-positive cocci, but more important, they are effective against H. influenzae and M. catarrhalis, including the ampicillin-resistant strains. Pneumococci resistant to penicillin (intermediate level) can be controlled with cefuroxime or similar agents, such as cefprozil (Cefzil) or cefpodoxime (Vantin), but these agents are ineffective against high-level resistant pneumococci. Cefpodoxime and loracarbef (Lorabid) are so similar to cefuroxime in activity and use that for simplicity they can be considered second-generation equivalents. As oral preparations, these agents are useful in managing acute sinusitis and otitis media. For intracranial complications of acute sinusitis or otitis media, cefuroxime penetrates the blood-brain barrier fairly well.
Third-generation cephalosporins include three of special importance in the management of infections of the ear, nose, throat, head, or neck. Cefixime (Suprax) is an oral agent highly active against H. influenzae and M. catarrhalis, even the ampicillin-resistant strains. Acute sinusitis and otitis media caused by these organisms can be managed effectively with once-daily dosing in a tablet or suspension preparation. If treatment fails, the infection probably is pneumococcal, against which this third-generation agent is less effective than are the first- and second-generation agents. Ceftibutn (Cedax) is roughly equivalent to cefixime.
Ceftriaxone (Rocephin) is a parenteral agent effective against H. influenzae, M. catarrhalis, S. pneumoniae, including most penicillin-resistant strains, Neisseria meningitidis, and Neisseria gonorrhoeae. Because it penetrates into the cerebrospinal fluid and because it has a broad spectrum of activity against organisms that cause upper respiratory infections, ceftriaxone usually is the first choice for treating patients with intracranial and orbital complications of acute sinusitis and otitis media. It is also the first choice for treating patients with oral gonococcal infections. Ceftriaxone has been found useful for single-dose injection therapy for acute and subacute otitis media. In many respects, cefotaxime (Claforan) is an equivalent agent. Ceftazidime (Fortaz) is a parenteral agent highly active against P. aeruginosa. It is also active against other gram-negative bacteria, including H. influenzae and N. gonorrhoeae, and it penetrates well into the cerebrospinal fluid. In general, third-generation cephalosporins are less active against gram-positive bacteria, such as Staph. aureus, than are their first-generation counterparts. Anaerobic bacteria, such as Bacteroides fragilis, also are relatively resistant.
Other b-Lactam Antibiotics
Imipenem (combined with cilastatin in Primaxin) and meropenem (Merrem) are parenteral agents that exert a broad spectrum of antimicrobial activity. They are active against S. pyogenes, most S. pneumoniae organisms, Staph. aureus (except methicillin-resistant strains), H. influenzae, B. fragilis and most anaerobic organisms, and the coliforms, including P. aeruginosa. Because of its broad spectrum, imipenem or meropenem can be used as a single agent against infection by unidentified organisms, but cerebrospinal fluid penetration is not assured. Because resistance can appear during therapy for pseudomonal infections, a b-lactam agent should not be used as a single agent. Patients with penicillin allergies may be allergic to imipenem. Aztreonam (Azactam) is a parenteral agent active against aerobic gram-negative organisms such as P. aeruginosa. Its distinguishing feature is its safety in the treatment of patients with penicillin allergies.
Erythromycins are effective therapy for respiratory infections due to streptococci, most pneumococci, mycoplasmata, and chlamydiae, legionellosis, diphtheria, and pertussis. Most Staph. aureus infections are susceptible to erythromycins, but resistance can develop during therapy. Management of H. influenzae infection with erythromycins is effective if a sulfonamide is added to the regimen (the combination Pediazole). Pneumococci resistant to penicillin are likely resistant to macrolides as well.
Preparations have been devised to minimize the degree of nausea and vomiting that accompanies use of erythromycin. The ethylsuccinate preparation can be taken with meals. Others need enteric coatings. Newer macrolides such as azithromycin (Zithromax) and clarithromycin (Biaxin) are more tolerable in terms of gastrointestinal effects. More important, they extend their antimicrobial activity to include H. influenzae and M. catarrhalis. Erythromycins and clarithromycin elevate theophylline levels with stimulating side effects if the drugs are taken concomitantly.
Clindamycin (Cleocin, oral or parenteral) is highly active against gram-positive cocci, including many but not all strains of penicillin-resistant pneumococci. Clindamycin is especially effective in the management of Staph. aureus infection, including infection with many methicillin-resistant strains. It is also highly effective against anaerobic infections of the aerodigestive tract, particularly with B. fragilis, which causes infection deep in the neck and draining ears and causes septic shock. Osteomyelitis is successfully managed with clindamycin because the organism is concentrated in bone. The combination of clindamycin and gentamicin is effective prophylaxis against all the common contaminants of surgical wounds, such as Staph. aureus, P. aeruginosa, and anaerobic organisms.
Nausea or diarrhea is sometimes intolerable after oral administration. Pseudomembranous colitis due to overgrowth of enteric Clostridium difficile is a serious complication attributed to clindamycin, but it also can complicate therapy with many other broad-spectrum agents. Treatment requires oral metronidazole or vancomycin. Patients who need clindamycin may be pretreated for several days with metronidazole to prevent colitis.
Tetracyclines are effective against Mycoplasma, Chlamydia, and Legionella infections. Most streptococcal, staphylococcal, and H. influenzae infections are resistant to tetracyclines, which means these drugs should be recommended only after culture studies show susceptibility of the infecting organisms. Because tetracyclines stain enamel in forming teeth, use of these agents is avoided in the care of children younger than 10 years and of women who may be pregnant. Tetracyclines predispose users to sunburn. Milk products and antacids (calcium, magnesium) interfere with absorption.
Chloramphenicol (Chloromycetin, oral and intravenous) exerts broad-spectrum activity against gram-positive cocci, including most penicillin-resistant Staph. aureus, and most gram-negative bacteria, including H. influenzae and the anaerobic organisms of the aerodigestive tract. Pseudomonas organisms, however, are resistant, as are penicillin-resistant strains of pneumococci. Chloramphenicol penetrates readily into the cerebrospinal fluid. Fatal bone marrow depression occurs among 1 of 24,000 patients who take chloramphenicol. This limits its use to management of life-threatening infection when other effective agents are unavailable, as in intracranial extension of sinusitis or otitis media in a patient with a history of anaphylactic reaction to b-lactam agents, such as penicillin.
The quinolone-fluoroquinolone group of antibiotics has a broad spectrum of effectiveness. They are useful in the management of infections that are resistant to several drugs. They have the additional advantage of being structurally unrelated to other classes of antibiotics, so they may be used to treat patients who are allergic to penicillins, sulfonamides, erythromycin, or cephalosporins.
Ciprofloxacin (Cipro) and ofloxacin (Floxin) are called antipseudomonas quinolones. They are important because of their effectiveness in controlling P. aeruginosa infection when given orally. Ciprofloxacin has greater therapeutic potency and causes fewer adverse side effects than does ofloxacin. Both agents elevate theophylline levels if such drugs are taken concomitantly. Ciprofloxacin has been effective in the treatment of patients with cystic fibrosis who have bronchitis, of those with pseudomonal sinusitis, and of those with malignant necrotizing otitis externa.
Levofloxacin (Levaquin), trovafloxacin (Trovan), gatifloxacin (Tequin), moxifloxacin (Avelox), and gemifloxacin (Factive) are classified as respiratory quinolones and are useful in the management of respiratory and pharyngeal infections. They are effective against b-hemolytic S. pyogenes, S. pneumoniae, including penicillin-resistant strains, and Staph. aureus, including methicillin-resistant strains. They also are active against H. influenzae and M. catarrhalis, including b-lactamase-producing strains, and against atypical pathogens such as Mycoplasma, Chlamydia, Legionella, and Bordetella pertussis organisms. They have the advantage of being long acting, so once-a-day dosing is effective. They are best absorbed if taken 1 hour before milk, antacids, or vitamin preparations that contain minerals.
Gatifloxacin, moxifloxacin, and trovafloxacin are the more potent antibiotics in this group. They are also active against anaerobic organisms such as Bacteroides and Peptostreptococcus. Because of reported adverse reactions, including liver damage, trovafloxacin preparations have been removed from the market. Intravenous trovafloxacin is used primarily in cases of severe or life-threatening infections, such as meningitis, when there are no other good options.
Vancomycin (Vancocin, parenteral) is highly active against gram-positive cocci, including methicillin-resistant strains of Staph. aureus, penicillin-resistant strains of pneumococci, enterococci, and gonococci. Because it is unrelated to any other class of antibiotics, vancomycin is useful in the treatment of patients with penicillin allergies. High concentrations in the serum of patients with renal impairment can cause ototoxicity. Vancomycin does not cross the blood-brain barrier effectively, so when resistant pneumococcal infections extend intracranially, vancomycin therapy should be combined with ceftriaxone or trovafloxacin. Because vancomycin may be the last remaining agent still effective against highly resistant strains of staphylococci, pneumococci, and enterococci, this drug should be reserved for such serious infections and not used against bacteria that can be effectively controlled with other antimicrobial agents.
Metronidazole (Flagyl, oral or parenteral) is highly active against anaerobic bacteria, including B. fragilis. It is useful in management of oral infections. All aerobic bacteria are resistant to this agent, but combination therapy (metronidazole plus any of the penicillins, cephalosporins, or quinolones) can be recommended to manage deep neck abscesses, chronic sinusitis, draining cholesteatoma, and intracranial extension of these infections. Metronidazole penetrates the blood-brain barrier well. Against antibiotic-induced pseudomembranous enterocolitis, metronidazole is much less expensive than vancomycin and is the preferred choice. Alcohol should not be consumed by patients taking metronidazole lest a reaction such as that to disulfiram (Antabuse) occurs.
Systemic aminoglycosides are administered by the parenteral route only. Gentamicin, tobramycin, and amikacin are used against P. aeruginosa and other hospital-acquired infections, such as Serratia infection. Gentamicin (generic) is inexpensive and usually is used as the first-choice agent in this category unless resistance is expected and the infection is progressing rapidly. Resistance to gentamicin does not necessarily imply resistance to tobramycin and amikacin, which are used as alternatives. For serious pseudomonal infection, treatment is improved if aminoglycosides are combined with antipseudomonal penicillins, such as tobramycin plus ticarcillin. These combinations produce a synergistic effect that reduces resistance or retards its emergence.
Anaerobic infections are almost universally resistant to aminoglycosides, as are 10% or more of Staph. aureus infections. A combination of gentamicin with clindamycin eliminates this problem. This combination is highly effective in the management of head and neck wounds with mixed infections and deep neck infections, and it provides excellent prophylaxis against surgical wound infections.
Ototoxicity of these agents places constraints on parenteral use, particularly of streptomycin, kanamycin, and neomycin. The incidence of aminoglycoside ototoxicity for gentamicin, tobramycin, and amikacin is commonly stated as approximately 10%, but it is worse among patients with impaired renal function, which allows toxic serum levels to accumulate. Careful monitoring indicates the dosages needed to avoid ototoxicity (2).
Rifampin is an important oral agent for managing the nasopharyngeal carrier state of H. influenzae and meningococcus. In combination with other antistaphylococcal drugs, such as ciprofloxacin, it controls resistant Staph. aureus and resistant pneumococci. It is sometimes combined with clindamycin or a second-generation cephalosporin. Mupirocin (Bactroban) ointment plus oral rifampin is useful in the management of chronic staphylococcal infection of the nostrils.
Sulfonamides are older agents effective in the management of H. influenzae infection but not of pneumococcal, streptococcal, and staphylococcal infections; however, sulfonamides may be used in combination with penicillin, cephalexin, macrolides (erythromycins), or even clindamycin to broaden the antimicrobial spectrum of coverage of these agents. Sulfonamides commonly cause rashes and photosensitivity (sunburn). Sulfamethoxazole plus trimethoprim (Bactrim, Septra) in combination is more potent than either agent alone.
The physician’s choice of antimicrobial agent is influenced by the following factors: (a) probable infecting organism, site of infection, and community prevalence, (b) probability of resistance to agent, (c) patient intolerance or allergy to agent, and (d) cost of agent. For example, amoxicillin may be an inexpensive first choice to manage acute otitis media, but it is not for the approximately 10% of patients with infections by organisms resistant to the drug. For physicians or patients who would be highly dissatisfied with the possibility of a treatment failure, one of the more expensive alternatives may be a better first choice. Physician and patient preferences and special situations may take precedence over the general recommendations listed in Table 5.1. Most well-established acute infections necessitate 10 days of therapy. Treatment begun very soon after the onset of infection may be of shorter duration. Chronic infection may necessitate several weeks or months of treatment and may not clear without surgical drainage.
Acute otitis media is caused by S. pneumoniae, H. influenzae, or M. catarrhalis, also known as Branhamella catarrhalis. Amoxicillin controls most strains of S. pneumoniae, but more than 20% of strains of H. influenzae are resistant, as are more than 80% of strains of M. catarrhalis. Erythromycin plus sulfonamide is slightly more expensive than amoxicillin, but it is more likely to clear the infection because it covers all the pathogens except penicillin-resistant pneumococci. Amoxicillin with clavulanate also is used to control the common pathogens, as are cefuroxime, cefprozil, and cefpodoxime. Cefixime can be administered once a day in a pleasant-tasting suspension for management of H. influenzae and M. catarrhalis infection, but failures are probable caused by pneumococcal resistance. Ceftibuten is similar to cefixime.
Penicillin-resistant pneumococci are prevalent pathogens among children who have received prolonged low-dose antimicrobial prophylaxis and those exposed to other children in large day-care centers. They pose special treatment problems. In a study conducted in New York City, investigators found pneumococcus in 26% (31 of 115) of middle ear aspirates from children with otitis media (4). Nonsusceptible strains were identified in 16% of the pneumococcal infections, and only cefuroxime had consistent activity against the moderately resistant strains. Another set of investigators (5) emphasized the growing prevalence of penicillin-resistant S. pneumoniae and its association with the use of two or more antibiotics to manage pediatric upper respiratory tract infections. The authors emphasized the need for continuing education of primary care physicians.
Intermediate-level resistance usually responds to amoxicillin with or without clavulanate, especially if dosages are high. An alternative is to administer ceftriaxone by means of injection. High-level resistance necessitates vancomycin therapy or possibly a quinolone frequently used to manage respiratory tract infection—levofloxacin, gatifloxacin, moxifloxacin, or gemifloxacin. Chronic otitis media with effusion is caused by the same pathogens as acute otitis media and is managed with the same antimicrobial agents.
Acute sinusitis is caused by the same bacteria as acute otitis media. Drug choices are the same; however, if sinusitis extends intracranially, pneumococcal infection is suspected, and agents must be selected that penetrate the blood-brain barrier, such as ceftriaxone, cefuroxime, or trovafloxacin. Orbital extension implies impending central nervous system extension, and it is similarly managed. Chronic sinusitis is caused by a mixture of various anaerobes that frequently includes Staph. aureus. Clindamycin or amoxicillin-clavulanate is a rational choice. Various fungi and Pseudomonas organisms in extensive polyposis also may be causative. Itraconazole (Sporanox) controls fungi. Ciprofloxacin controls Pseudomonas infection.
Pharyngitis is caused by S. pyogenes among 30% of persons with sore throats during the winter months as ascertained with throat culture studies; however, N. gonorrhoeae, Mycoplasma, Chlamydia, and Haemophilus organisms are other important causes of sore throat that can be controlled with antimicrobial therapy. Other likely agents are the anaerobic organisms involved in tonsillitis. Diphtheria is rare. All of these organisms produce negative “strep” cultures of the throat, which illustrates the folly of routinely withholding antibiotic therapy until strep culture results prove positive. Clinical judgment is required. Factors that favor bacterial infection and the need for antibiotic treatment include (a) a history of bacterial infection in the household, (b) prolonged or severe sore throat, (c) severe erythema, exudate, or lymphadenopathy, (d) absence of hoarseness, which indicates viral laryngitis.
Tonsilloadenoiditis is most frequently caused by S. pyogenes, but a variety of anaerobic organisms often are present in a mixed infection. These commonly produce b-lactamase enzymes that render penicillin ineffective even against the streptococci. Therefore, clindamycin often is more effective. Augmented amoxicillin also is effective, but if mononucleosis is the principal infection, amoxicillin has a 50% probability of producing a severe rash. Clindamycin, cephalexin, or penicillin plus metronidazole can avoid that problem. Extensive exudate on the tonsils suggests mononucleosis among adolescents and children. Antibiotic therapy may not control Epstein-Barr virus, but it does control secondary bacterial invaders.
Acute laryngitis usually is a viral infection that resolves with a few days of voice rest. Prolonged hoarseness suggests a secondary bacterial infection to be controlled with erythromycin or another macrolide plus sulfonamide or a quinolone commonly used to manage respiratory tract infection.
Epiglottitis is most frequently caused by H. influenzae. Parenterally administered sulbactam-ampicillin, cefuroxime, or ceftriaxone is a rational choice. Trovafloxacin administered intravenously can be used to treat patients with a history of penicillin anaphylaxis. Airway management takes priority.
Croup (subglottic) usually is a viral infection, but 10% of patients have secondary infections with Staph. aureus or H. influenzae. If thick yellow secretions are encountered, administer the same agents as used for epiglottitis.
Deep neck abscesses and wounds subjected to mucosal infection or chronic intracranial infection of ear or sinus origins are caused by mixed bacterial flora with anaerobic organisms predominating. Clindamycin covers Staph. aureus, all cocci, and anaerobic organisms, but when pseudomonal infection is suspected, gentamicin should be added. Neither of these agents, however, reliably penetrates into central nervous system tissues, for which nafcillin plus metronidazole is needed. If Haemophilus or pseudomonal infection is anticipated, ceftazidime can be administered. Trovafloxacin administered intravenously and vancomycin are contingency drugs for patients with a history of penicillin anaphylaxis.
Management of acute mastoiditis with subperiosteal abscess requires coverage of the same microbial possibilities as acute otitis media. Pneumococci and H. influenzae tend to intracranial extension. Ceftriaxone is the initial choice. Chronic suppurative otomastoiditis, including cholesteatoma, adds Staph. aureus, Proteus organisms, B. fragilis, and other anaerobic organisms to the infectious polymicrobial mix. Smelly pus suggests the presence of anaerobic bacteria. Pseudomonas also is a frequent contaminant. Intracranial extension necessitates use of combinations that penetrate the central nervous system, such as ceftazidime plus augmented ampicillin or ceftazidime plus metronidazole plus nafcillin.
Ototopical therapy is only as effective as the cleanings the physician provides, because infection advances in the opposite direction as the drainage flows. The draining ear of acute otitis externa or suppurative otitis media necessitates combination drug therapy—polymyxin for the pseudomonal infection and neomycin for the Staph. aureus, Proteus organisms, and others. Either of these agents alone is likely to produce treatment failure; Cortisporin or Coly-Mycin S includes both. Some Pseudomonas organisms are resistant to polymyxin, but gentamicin drops can be added to or alternated with the Neosporin-polymyxin preparation. Quinolone otic drops such as ciprofloxacin and ofloxacin are highly effective, and they are particularly indicated in the treatment of patients with a tympanic membrane that is not intact. In a study involving 381 patients with chronic suppurative otitis media, investigators found that Pseudomonas organisms (27%) and Staph. aureus (24%) were the important organisms isolated. Topical aural preparations of ciprofloxacin and gentamicin were the most effective agents (6).
Otomycosis due to Aspergillus infection usually is managed with acidifying ear drops that contain acetic or boric acid, such as Acetasol and Domeboro. Other antiseptics, such as Merthiolate, gentian violet, and iodine, sometimes are used. Topical antifungal agents, such as clotrimazole (Lotrimin) work for candidiasis. Tom (7) reported that according to results of studies of animals, clotrimazole, miconazole, and tolnaftate appear to be safe in terms of ototoxicity, but entian violet can cause severe damage. The residue left by the nystatin preparation is cause for concern and a reminder that both the active ingredient and the vehicle must be considered in terms of safety.
If cellular tissue levels of properly selective antibiotics are high at the moment of contamination, such as incision, surgical wound infections and sepsis are remarkably reduced. Prophylaxis for surgical wound infections requires administration of the initial dose an hour or so before incision time and continuation for 24 hours or until the period of wound contamination, such as suture line leakage, has passed. For incisions through the skin, staphylococcal infection must be addressed, and cefazolin is the most commonly used agent. Incisions through mucous membranes, especially pharyngeal membranes, can cause contamination by anaerobic organisms. Wound breakdown among hospitalized patients carries risk of pseudomonal infection. Gentamicin plus clindamycin covers all these contingencies. This prophylaxis yields excellent results in head and neck tumor surgery. Postoperative infection associated in uninfected nasal or otologic operations are so uncommon that statistical proof of the efficacy of prophylaxis is unlikely. If prophylaxis is justified, it is by inference from its effectiveness in surgical procedures in general. If the risk of a serious or poor outcome outweighs the risk or cost of administration of antibiotics, treatment may be advisable.