This action might not be possible to undo. Are you sure you want to continue?
Antibiotic selection in head and neck infections
Thomas R. Flynn, DMDa,b,*, Leslie R. Halpern, DDS, MD, MPH, PhDa,b
Department of Oral and Maxillofacial Surgery, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA b Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
Oral and maxillofacial surgeons see patients with infections as part of their everyday practice. It is imperative to understand the mechanisms of antimicrobial resistance, its potential problems, and the means of overcoming it. This situation raises several important questions with respect to antimicrobial therapy for odontogenic infections: 1. Is there a problem of antibiotic resistance? 2. How does antibiotic resistance arise? 3. Is antibiotic resistance the fault of the bacteria or the host or the result of treatment (ie, the medical and surgical community)? 4. What can be done to remedy the problem? The purpose of this article is to examine the problem of antimicrobial resistance in the oral cavity and make recommendations for antibiotic selection in the treatment of head and neck infections.
The acquisition of antibiotic resistance genes by bacteria allows such mechanisms to be implemented. There are four specific mechanisms by which bacteria acquire resistance genes: 1. Spontaneous mutation. This is the original source for all antibiotic resistance, because bacteria have maintained genes that encode for resistance of naturally occurring antibiotics of other species. For example, the DNA encoding of b-lactamases and penicillinbinding proteins have several homologous sequences . 2. Gene transfer. Bacteria can undergo conjugation with a transfer of genes as plasmids, which are a composition of cytoplasmic loops of DNA that encode for antibiotic resistance, and transposons, which are able to insert themselves into the genome of the recipient cell. An example of a plasmid-mediated genetic event is acquisition of the ability to produce b-lactamase by some species. 3. Bacteriophages. Viruses infect bacteria and can insert genetic material and take control of the host’s genetic and metabolic machinery, which may encode for antibiotic resistance mechanisms. 4. Mosaic genes. Bacteria can absorb directly the fragments of the virally altered genome of dead members of related species to form a ‘‘mosaic genome’’ of genetic material from varying sources. This type of gene derivation is responsible for the non – b-lactamase penicillin resistance in Streptococcus pneumoniae and meningococci and ampicillin resistance in Haemophilus influenzae and gonococci .
Molecular biology of antibiotic resistance Generally speaking, bacteria acquire antibiotic resistance in one of four ways: 1. 2. 3. 4. Alteration of a drug’s target site Inability of a drug to reach its target Inactivation of an antimicrobial agent Active elimination of an antibiotic from the cell
* Corresponding author. Department of Oral and Maxillofacial Surgery, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115. E-mail address: firstname.lastname@example.org (T.R. Flynn).
1042-3699/03/$ – see front matter D 2003, Elsevier Science (USA). All rights reserved. PII: S 1 0 4 2 - 3 6 9 9 ( 0 2 ) 0 0 0 8 2 - 1
T.R. Flynn, L.R. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38
Antibiotic resistance mechanisms Once the genetic machinery is in place, bacteria exert antibiotic resistance by various pathways that are broadly classified in four ways. Drug inactivation or modification. The destruction or inactivation of the antimicrobial agent is accomplished by the induction of specific drug-inactivating enzymes, such as those that inhibit b-lactams or aminoglycosides. Numerous gram-positive and gram-negative bacteria, such as Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, H. influenzae, Bacteroides, and many strains of Prevotella have this capability. Another method used by bacteria to withstand antimicrobial attack is the ability to synthesize neutralizing enzymes. The best examples are penicillinase and the methylation of erythromycin and clindamycin. Other antibiotics that are neutralized include vancomycin, sulfonamides, aminoglycosides and rifampin. Bacterial organisms with this capability include S. pneumoniae, S. aureus, Clostridium perfringens, Bacteroides fragilis, Campylobacter species, and Neisseria gonorrhoeae. Alteration of microbial membrane permeability. Alterations in membrane permeability can cause decreased uptake or increased efflux of the antibiotic. The types of antibiotics most often affected by this mechanism are the b-lactams, quinolones, tetracyclines, erythromycin, and the aminoglycosides. The gram-negative rods E. coli, P. aeruginosa, and Salmonella typhimurium also have this capability. Porins within the transmembrane protein matrix are specific for various antibiotics, and the loss of a specific porin confers resistance. Lack of the D2 porin, for example, confers imipenem resistance in P. aeruginosa. Increased efflux of the antibiotic before lethal damage occurs is seen in the Enterobacteriae with the mar, norA, and tetA genes, which convey resistance by pumping tetracycline out of the cells. E. coli and Staphylococcus epidermidis also can resist tetracyclines, macrolides and quinolones by this mechanism [1,2]. Alteration of target site. Enzymes responsible for cell wall synthesis, the transpeptidases, can be altered slightly to produce less affinity for penicillins. These altered penicillin-binding proteins are most often seen in S. aureus and S. pneumoniae . Alteration in the concentration of drug target receptors. Many of the gram-negative rods (ie, E. coli and Proteus, Enterobacter, and Klebsiella species) have the ability to alter the number of drug receptors that bind antibiotics. The sulfonamide family is affected by such a mechanism.
Strategies in the prevention of antibiotic resistance Extending surgical prophylaxis beyond 48 hours and inappropriately low dosing that encourages subpopulations of organisms to survive in increasing concentrations of antibiotics can select for resistant bacteria . Although culture and sensitivity studies are crucial and should not preclude empiric therapy when warranted, there is also the risk that the latter can produce bacterial resistance. A case series to examine the bacteriology of dentoalveolar abscesses in patients who received empiric antibiotic therapy suggested that the polymicrobial nature of the abscess and the administration of empiric therapy with ampicillin or cephalosporins often results in resistant strains . The predominant species were anaerobic (ie, Prevotella and Peptostreptococcus species, both resistant to the therapy initially given). Kuriyama et al  examined the relationship between past administration of b-lactamase antibiotics and an increase in b-lactamase – producing bacteria in patients with odontogenic infections. The algorithm of treatment derived from their study is a course of b-lactamase antibiotics for 1 to 2 days, but if the infection is unresolved by 3 days or more, one should assume the presence of b-lactamase – producing organisms, and treatment should involve a penicillinase-stable b-lactam or a non – b-lactam antibiotic. No definitive studies with large sample sizes clearly define ways to manage antibiotic resistance in odontogenic infections, however. The question of whether antibiotic resistance in patients with odontogenic infections who need hospitalization is caused by the therapeutic modality given, the characteristics of the patient population, or the ability to isolate and characterize more carefully the vector of disease is paramount because of the possibility that the increased incidence of antibiotic-resistant strains is an unavoidable direct effect of therapy. Retrospective studies that compared populations decades apart have shown that although no clinically significant differences exist between cohorts examined, there are differences in types of microorganisms in terms of their nomenclature [6,7]. Flynn et al  performed a prospective study of 34 hospitalized patients with odontogenic infections and found a 26% rate of clinical failure with penicillin therapy and a 60% rate of penicillin resistance. This finding is exemplified by data on treatment of upper respiratory tract infections. In a study of children with pharyngitis, Brook  found a 9% incidence of penicillin resistance in throat swab cultures at the initiation of treatment. After 1 week
The number declined to 27% in the subjects over the ensuing 3 months. Fortunately. corrodens should be considered a possible pathogen in treatment failure of odontogenic infections and routinely in animal bite wounds . This fact suggests the selection of the penicillins over other . Odontogenic infections are generally characterized by a combination of facultative streptococci and oral anaerobes. hypersensitivity reaction to clindamycin. other members of the viridans streptococci. Approximately 10% to 15% of penicillin-allergic patients are also sensitive to the cephalosporins. aeruginosa. Within the viridans group of facultative streptococci. The factors that must be considered can be categorized into host-specific and pharmacologic factors. metronidazole. The clinician must keep in mind the occasional pathogen that is resistant to the usual empiric antibiotic of choice. Eikenella corrodens is fairly resistant to the penicillins and completely resistant to clindamycin. All clinicians should be aware of the potential for cross-allergy between the penicillins and other members of the b-lactam group. alternatively. The penicillin-sensitive streptococci predominate during the first 3 days of clinical symptoms. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 19 of penicillin therapy. L. and macrolide (erythromycin family) intolerance and drug interactions are frequent. and S. The penicillins are the antibiotics most frequently prescribed for infections in the oral cavity. Although the peptostreptococci remain penicillin sensitive. constellatus. 46% of the subjects and 45% of the subjects’ parents and siblings harbored resistant strains. Klebsiella pneumoniae. Host factors in antibiotic selection Usual pathogens The type of infection that presents can be characterized by cause and location. the Streptococcus milleri group. and Clostridium difficile . The fluoroquinolones have become the antibiotic of choice for this pathogen. is a rare event. approximately 25% of strains of Prevotella and Porphyromonas are penicillin resistant . Between 1% and 10% of patients who initially take penicillin develop an allergic reaction. from the family. and Streptococcus salivarius. are more frequently found in endocarditis. subsequent skin testing proved that more than 60% of patients were not allergic to either penicillin or other b-lactams. Cross-sectional studies of penicillin allergy indicate that in many hospital chartings of penicillin allergy. Issues in antibiotic selection The selection of an appropriate antibiotic for a given case can be complex. Flynn. Another factor is the severity of the odontogenic infection. Streptococcus sanguis. but usually it is a straightforward process. The cross-allergic group tends to include persons who have had an anaphylactoid reaction to the penicillins. The usual flora of various types of head and neck infections are listed in Table 1. and the more resistant gram-negative obligate anaerobes appear in significant numbers thereafter. On the other hand. and they can be highly penicillin resistant—up to 58% in one study . Allergy or intolerance A history of antibiotic allergy is usually readily obtained from the conscious patient or. Among the anaerobes. S. This is fortunate because only approximately 3% of the strains of these species are resistant to the penicillins. or newer antibiotics may be prudent when anamnestic information is unavailable. little or no difference was found between the effectiveness of penicillin and various other antibiotics in outpatient odontogenic infections [11 – 14]. and persons who do not develop a reaction have less than a 1% chance of developing an allergy with reexposure . The choice of clindamycin. Several hospitals have substituted the cephalosporins for penicillin/b-lactamase inhibitor combinations.18]. E. antibiotics in early cases. P. which consists of S. On the other hand. such as Streptococcus mitis. Flynn et al  found a clinical failure rate of 26% for penicillin in hospitalized cases. It is not surprising that their use is associated with hypersensitivity reactions. anaerobic peptostreptococci and members of the genera Prevotella and Porphyromonas predominate.T.R. is most frequently associated with orofacial cellulitis and abscess. which in some cases has resulted in dramatic recovery of antibiotic susceptibility rates among pathogens such as Enterobacter cloacae. intermedius. with or without an aminoglycoside. and each has its own characteristic flora. In odontogenic infections and dog and cat bites. which warrants more careful vigilance by doctors who are recording medical histories and allergies of their patients [17. Penicillin allergy is common. The cephalosporins should be avoided in these patients.R. anginosus. It is judicious to clarify whether the person has a true allergy to penicillin. often substituted in penicillin-allergic patients.
HIV-infected individuals seem to be able to handle oral bacterial infections almost as well as noninfected persons.20 T. are prevalent in poorly controlled HIV-infected individuals. a bactericidal rather than bacteriostatic antibiotic should be selected whenever possible. This stratagem should result in a more rapid clinical response. Flynn. seem to be bacteriostatic at lower doses and bactericidal at higher doses. Escherichia coli) S. such as phototoxicity with the tetracyclines or antibioticassociated colitis with clindamycin. the monobactams (aztreonam) and the carbapenems (imipenem and meropenem). Immune system compromise Because the immunocompromised patient is less able to kill invading pathogens by host resistance mechanisms. or with nucleic acid synthesis. . Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 1 Major pathogens of head and neck infections Type of infection Odontogenic cellulitis/abscess Microorganisms Streptococcus milleri group Peptostreptococci Prevotella and Porphyromonas Fusobacteria Streptococcus pneumoniae Haemophilus influenzae Head and neck anaerobes (peptostreptococci. which arrests vital processes. L. would preclude its subsequent use unless strongly indicated. aureus and skin flora in trauma Salmonella in sickle cell disease Actinomyces species Group A b-hemolytic streptococci Regional flora (oral and sinus pathogens in head and neck) Candida species Histoplasma species Blastomyces species Aspergillus Rhizopus (mucor) Rhinosinusitis Acute Chronic Fungal Nosocomial (especially if intubated) Osteomyelitis of the jaws Acute Chronic Necrotizing fasciitis Fungal Mucosal or disseminated Soft tissue Sinus The newer b-lactam antibiotics. Resistance to these common infections remains fairly robust until the terminal stages of AIDS. which are resisted by cell-mediated immunity (T cells). A history of adverse reaction or intolerance of an antibiotic.R. Acinetobacter. The bacteriostatic antibiotics interfere with protein synthesis. (mucor) Enterobacteriaceae (especially Pseudomonas. such as clindamycin. Some antibiotics. which causes lysis.R. On the other hand. fungal and viral infections. fusobacteria) Group A b-hemolytic streptococci Staphylococcus aureus Moraxella catarrhalis Viruses Head and neck anaerobes Aspergillus Rhizopus sp. which is largely responsible for combating the extracellular bacterial pathogens of most head and neck infections. have much less frequent cross-sensitivity with the penicillin group. The bactericidal antibiotics generally interfere with either cell wall synthesis. arresting growth and multiplication. aureus Yeasts (Candida species) Odontogenic flora S. Prevotella. Porphyromonas. This ability is probably caused by the antibody-mediated immunity provided by the B-lymphocytes. when all types of lymphocytes are severely depleted.
and the fluoroquinolones. aminoglycosides. Studies of patients who are currently taking or recently have taken antibiotics consistently yield a higher incidence and proportion of organisms resistant to that antibiotic [10.T. is paramount in the treatment of infections that threaten the central nervous system. Table 3 describes the general spectrum of selected antibiotics. salivarius) is high—up to 58%  in persons with a history of prior endocarditis. Penicillin G in high doses reaches 5% to 10% of the serum concentration in the cerebrospinal fluid Table 2 lists common antibiotics by their ability to kill bacteria or merely suppress their growth. and Tables 4 and 5 especially can be used in selecting an appropriate antibiotic for organisms identified by culture. mitis. and S. The antibiotic that best penetrates an abscess is clindamycin.6 mg/mL and 20 mg/mL. On the other hand.20]. The antibiotics that best penetrate or even accumulate in bone are the tetracyclines. the clinician has the choice of changing the current antibiotic or increasing its dose.19]. Special conditions Certain temporary host conditions may affect antibiotic selection. and saquinavir. The antibiotics effective against the highly resistant organisms are also included in Table 4.R. Table 4 lists the bacteria and fungi most likely to be encountered and the antibiotics of choice for those pathogens. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 2 Bactericidal and bacteriostatic antibiotics Bactericidal b-lactams penicillins cephalosporins carbapenems monobactams Aminoglycosides Vancomycin Metronidazole Fluoroquinolones Bacteriostatic Macrolides erythromycin clarithromycin azithromycin Clindamycin Tetracyclines Sulfa antibiotics 21 They are discussed in the section on adverse antibiotic reactions. such as childhood and pregnancy. ethambutol. has not been tested in a clinical study. clindamycin. The previous use of different antibiotics during the course of an acute infection definitely clouds the bacteriologic picture. This fact may partially explain the usefulness of clindamycin in odontogenic infections. for which sensitivity data may not be available. These data. . In patients with a history of endocarditis. The antibiotics that do not penetrate the cerebrospinal fluid well are clindamycin. This approach. these effects persist for a considerable time after antibiotic therapy and may be permanent [19. however. the abscess concentration of clindamycin reaches 33% of the serum level . Cerebrospinal fluid penetration. peak serum blood levels are 5. Clindamycin resistance of these bacteria in such patients remains low. itraconazole. The penicillin resistance rate of the endocarditisassociated viridans streptococci (S. sanguis. the macrolides (including clarithromycin and azithromycin). The antibiotics that can attain therapeutic levels in cerebrospinal fluid when the meninges are inflamed are listed in Table 6. it may be advisable to use clindamycin rather than amoxicillin for endocarditis prophylaxis before oral procedures. respectively. or the ability of an antibiotic to cross the blood-brain barrier. especially in osteomyelitis. With penicillins V (oral) and G (intravenous).R. Tissue distribution of antibiotics Although abscess cavities are not vascular. Bone penetration of antibiotics is an important consideration. S. among others. amphotericin. In this situation. L. Pharmacologic factors in antibiotic selection Antimicrobial spectrum The most important pharmacologic consideration in antibiotic selection is whether it is effective against the likely pathogens. Flynn. and most other cephalosporins (except those listed in Table 6). perhaps by using the parenteral route. are used in constructing the recommendations for empiric antibiotics of choice for various head and neck infections. as in actual or impending cavernous sinus thrombosis. Table 5 lists the antibiotics to which selected highly resistant organisms have become resistant. The dramatic increase in efficacy afforded by the parenteral route of administration may be more advantageous than changing to another antibiotic that is less effective than the penicillins. some penetration of antibiotics into these spaces does occur. Previous antibiotic therapy All antibiotic therapy inherently selects for resistant organisms. cefazolin.
not MRSE H. plus S. aureus.R. aureus. not MRSA S. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 3 Spectrum of selected antibiotics Antibiotic category Natural penicillins Antibiotic Penicillin G and V Susceptible organisms Viridans streptococci Oral anaerobes Actinomyces sp. not MRSE As with natural penicillins. catarrhalis Oral anaerobes Actinomyces (ceftriaxone) Streptococci Actinomyces Peptostreptococci (azithromycin) Streptococci Oral anaerobes Actinomyces S.R. Flynn. not MRSA H. catarrhalis Klebsiella species E. plus S. plus M. epidermidis. not MRSA Enterobacteriaceae (most) (continued on next page) Semisynthetic penicillins b-lactam/b-lactamase inhibitors Ampicillin Amoxicillin Amoxicillin/clavulanate Ampicillin/sulbactam Penicillinase-resistant penicillins Antipseudomonal penicillins Oxacillin Dicloxacillin Ticarcillin/clavulanate Piperacillin/tazobactam Carbapenems Monobactam Cephalosporins Imipenem Meropenem Ertapenem Aztreonam First generation Cephalexin Cefazolin Second generation Cefaclor Cefuroxime Cefoxitin Third generation Cefotaxime Ceftriaxone Macrolides Erythromycin Clarithromycin Azithromycin Clindamycin Clindamycin Metronidazole Fluoroquinolones Ciprofloxacin . coli As with first generation. not MRSA S. aureus. aureus. epidermidis. catarrhalis Klebsiella species E. aureus. coli Bacteroides fragilis Enterobacteriaceae (most) Pseudomonas aeruginosa As with antipseudomonal penicillins.22 T. not MRSE H. (penicillin G only) Pasteurella multocida As with natural penicillins. influenzae M. plus M. influenzae Klebsiella E. coli Bacteroides fragilis S. catarrhalis (cefuroxime) Oral anaerobes B. influenzae M. not MRSA S. plus Actinomyces (imipenem) Enterobacteriaceae. epidermidis. aureus. L. fragilis (cefoxitin) As with first generation. except Salmonella (no data) and Acinetobacter (resistant) Streptococci S. not MRSA Obligate anaerobes S. plus enterococci Actinomyces As with amoxicillin.
5 hours. 50% of the remaining penicillin is eliminated from the serum. or 2. aureus. the remaining serum concentration of amoxicillin should have fallen below the MIC-90 of the viridans streptococci at approximately 2. including MRSE (vancomycin) Streptococci Staphylococci. such as the b-lactams and vancomycin. MRSE Legionella Streptococci S. Using the same analysis. In concentration-dependent antibiotics. MRSE Peptostreptococci Enterococci. the peak blood level achieved with amoxicillin. is concentration dependent.15 mg/mL. VRSE. usually 50% or 90%. The serum level will have fallen below the MIC-90 roughly for only the last 15% of the dosage interval. the addition of metronidazole (30% – 100% penetration) to ampicillin (13% – 14% penetration) is more efficacious than using penicillin G alone . 500 mg orally. vancomycin-intermediate S. including MRSA S. VRSE. VISA. including VISA. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 3 (continued ) Antibiotic category Antibiotic Moxifloxacin Susceptible organisms 23 Aminoglycosides Gentamicin Tobramycin Glycopeptides Vancomycin Teicoplanin Linezolid Oxazolidinones Pristinamycins Quinupristin/dalfopristin Ketolides Telithromycin Streptococci Oral anaerobes S. L. whereas with other antibiotics. Flynn. Intravenous penicillin G.R.R. MRSA. epidermidis. catarrhalis Legionella Abbreviations: MRSA. VRSE. Pharmacokinetics The effectiveness of some antibiotics. aureus. methicillin-resistant S. which is the concentration of the antibiotic required to kill a given percentage of the strains of a particular species. epidermidis. vancomycin-resistant S. aureus. aureus. should be highly effective against the viridans group of streptococci. Oral amoxicillin therapy may not kill 90% of all the . In time-dependent antibiotics. it is necessary to maintain the serum concentration above the MIC for at least 40% of the dosage interval.5 mg/mL. During each half hour. MRSE. The MIC-90 for the viridans streptococci is 2 mg/mL for amoxicillin. MRSA.5 hours. efficacy is determined by the ratio of the serum concentration of the antibiotic to the minimum inhibitory concentration (MIC). is 7. it is time dependent. For example.2 hours.2 mg/mL and because the peak serum level achieved with 2 million U of intravenous penicillin G is 20 mg/mL. including VISA. when the meninges are inflamed. which is only 31% of the dosage interval. influenzae M. the serum concentration of penicillin after 4 hours (eight half-lives) is approximately 0. epidermidis. aureus. the t/2 of penicillin G is 0. only approximately 3% of the peak serum level of penicillin remains. It is necessary with time-dependent antibiotics to know the serum elimination half-life (t/2) of the antibiotic to determine its proper dosage interval. not MRSA Enterococci (gentamicin synergistic with ampicillin) Enterobacteriaceae (many) Pseudomonas Streptococci S. and its t/2 is 1. methicillin-resistant S.5 hours. In odontogenic infections that threaten the central nervous system. Because the MIC-90 of the viridans streptococci (the concentration that kills 90% of the strains) is 0. By five half-lives. including VRE Streptococci Staphylococci. such as the fluoroquinolones and aminoglycosides. Using an 8-hour dosage interval. 2 million U every 4 hours.T. aureus (not MRSA?) H. not MRSA Actinomyces B. fragilis Enterobacteriaceae (most) S.
F Linezolid + quinupristin/dalfopristin F Teicoplanin + aminoglycoside choramphenicol F doxycycline (van B) For some strains: no effective regimen (I. not cefotetan (DOT) Ampicillin/sulbactam +. Flynn. A Ticarcillin/clavulanate Aztreonam Cephalosporins Imipenem TMP/SMX Tobramycin Fluoroquinolones À . aminoglycoside and vancomycin resistant) Escherichia coli Fusobacterium species Haemophilus influenzae (b-lactamase positive) Klebsiella pneumoniae Klebsiella pneumoniae (producing extended spectrum b-lactamases: ESBLs) Pasteurella multocida (eg. A Imipenem/cilastatin Meropenem Fluoroquinolones À . F Ampicillin F gentamicin Vancomycin (for endocarditis or meningitis Ampicillin/sulbactam Linezolid +. A Salmonella typhi À . AN Metronidazole Clindamycin Cefoxitin. AN Metronidazole p. F Amoxicillin/clavulanate Cefotaxime (if life threatening) Cefaclor Ciprofloxacin Azithro/clarithromycin TMP/SMX À . R. A Penicillin G Amoxicillin/Clavulanate Doxycline Cephalosporin (2nd)a TMP/SMX Clindamycin Doxycline Vancomycin PCN + metronidazole Amoxicillin Cefotetan Tobramycin Imipenem Ticarcillin/clavulanate Aztreonam + ceftazidime Piperacillin + tobramycin Cefepime + tobramycin Chloramphenicol Amoxicillin TMP/SMX (continued on next page) +. A First choice antibiotics Penicillin G or ampicillin Alternative antibiotics Bacteroides fragilis Clostridium species (except C. L. R. R.24 T. Bacitracin p. R. R. A Fluoroquinolones Ceftriaxone . À .o.o. C. R. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 4 Antibiotics of choice for head and neck pathogens Pathogen Actinomyces Type +. R.R. R.D. A Cephalosporin (3rd)* Tobramycin Fluoroquinolones Ticarcillin/clavulanate Imipenem/cilastatin À . R. dog and cat bites) Peptostreptococcus (and former Peptococcus) Black pigmented oral anaerobes (Prevotella and Porphyromonas) Proteus vulgaris (indole +) Doxycycline Clindamycin Erythromycin À . R. difficile) Clostridium difficile Eikenella corrodens Enterococcus faecalis (group D streptococcus) Enterococcus faecium (group D streptococcus: b-lactamase +. AN Penicillin G F clindamycin Metronidazole Doxycycline Cephalosporin (1st)a +. A Penicillin G or V Fluoroquinolones Amoxicillin TMP/SMX (avoid Amoxicillin/clavulanate clindamycin) +. A Cephalosporin (3rd) Fluoroquinolones Ciprofloxacin Tobramycin Pseudomonas aeruginosa À .o. R. C. R. Vancomycin p. AN Penicillin G or V Metronidazole Clindamycin À . consultation) Meropenem for central nervous system À .R. R. AN Clindamycin À . R. C. AN Penicillin G or V À . R.
. A (Pneumococcus) (multiantibiotic resistant. and thetaiotamicron group of B. 32nd edition. C. cefipime Imipenem New fluoroquinolonesb Clindamycin New fluoroquinolones (in vitro) Penicillin G or V (+ gentamicin if serious group B infection) Penicillin G or V Cephalosporin (1st)a Erythromycin Cephalosporin (1st)a Macrolides Itraconazole (if surface) Fluconazole (if surface) Nystatin (if surface) Clotrimazole (if surface) Ketoconazole (if surface) Itraconazole (if surface) Fluconazole Amphotericin B Itraconazole (immunocompetent) Itraconazole (immunocompromised) Control underlying systemic disease Amphotericin B (for systemic cases) Fluconazole Amphotericin B (for systemic cases) Itraconazole Amphotericin B (for systemic or immunocompromised cases) Amphotericin B Coccidioides immitis Histoplasma Mucormyces Fungus Fungus Fungus Abbreviations: A. ovatus. A (a-hemolytic streptococcus) Fungal organisms Blastomyces Fungus Candida Fungus Vancomycin (high dose) New fluoroquinolones?b (rapid resistance a problem) Cefuroxime. and TMP/SMX) Streptococcus pyogenes +. DOT. A Vancomycin TMP/SMX + ampicillin Cephalosporin (1st)a Vancomycin Clindamycin Teicoplanin Quinupristin-dalfopristin TMP/SMX (some strains) Linezolid Quinupristin/dalfopristin Linezolid Quinupristin/dalfopristin Staphylococcus aureus (methicillin and vanco mycin resistant) Staphylococcus epidermidis (methicillin resistant) +. + = gram positive. gemi-. C. lero-. Moellering RC Jr. C. C. trimethoprim-sulfamethoxazole. C. C. rod. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 4 (continued ) Pathogen Serratia marcescens Type First choice antibiotics Alternative antibiotics Gentamicin Aztreonam 25 Shigella Staphylococcus aureus (methicillin sensitive) Staphylococcus aureus (methicillin resistant) À . R. tetracycline. The Sanford guide to antimicrobial therapy 2002. A No effective regimen Try vancomycin F rifampin Vancomycin (+ rifampin + gentamicin for prosthetic valve endocarditis) Quinupristin/dalfopristin Linezolid Penicillin G or V Ceftriaxone Amoxicillin Vancomycin + Rifampin +. penicillin. C. aerobe. C. including high-level penicillin. fragilis species. A (Pneumococcus) (penicillin sensitive) Streptococcus pneumoniae +. a Number in parentheses after cephalosporins refers to generations within the cephalosporin family. C. Flynn. chloramphenicol. A Cephalosporin (3rd) Imipenem Meropenem Fluoroquinolones À . TMP-SMX. F. moxi-. erythromycin. anaerobe. À = gram negative. R. New Hyde Park (VT): Antimicrobial Therapy Inc. A (b-hemolytic streptococcus) Streptococcus viridans +.T. A Staphylococcus epidermidis +. Sande MA. AN. L. facultative. PCN. coccus. distasonis.R. sparfloxacin. C. Data from Gilbert DN. A Penicillinase-resistant penicillin +. A (methicillin and glycopeptide resistant) Streptococcus pneumoniae +.R. . R. 2002. A Fluoroquinolones Azithromycin +. b New fluoroquinoles are gati-.
vancomycinresistant methicillin-resistant S. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 5 Highly resistant organisms and the antibiotics to which they are resistant Organism Acinetobacter baumanii Resistant to Penicillins Third generation cephalosporins Antipseudomonal aminoglycosides Fluoroquinolones Imipenem Glycopeptides Streptomycin Gentamicin All b-lactams Glycopeptides Aminoglycosides Glycopeptides Streptomycin Gentamicin all b-lactams Glycopeptides Aminoglycosides Penicillins Third generation cephalosporins Aztreonam Penicillins Cephalosporins Carbapenems Methicillin Methicillin Vancomycin only Vancomycin and teicoplanin (both available glycopeptides) Methicillin Methicillin Glycopeptides Penicillin G Enterococcus faecalis b-lactamase negative Enterococcus faecalis b-lactamase positive Enterococcus faecium b-lactamase negative Enterococcus faecium b-lactamase positive Klebsiella pneumoniae ESBL positive strains of the viridans streptococci. 2002. The use of antibiotics in pregnancy almost always involves an evaluation of risk versus benefit. Special conditions Antibiotics that should be avoided in children include the tetracyclines (under the age of 8). Data from Gilbert DN. ticarcillin. cephalosporins. Flynn. Hyde Park (VT): Antimicrobial Therapy. and clindamycin. The cost saving of once-daily intravenous dosing makes this approach appealing. quinine. and antibiotic-associated colitis with the b-lactam/b-lactamase inhibitor combinations (eg. Pseudomonas aeruginosa Staphylococcus aureus MRSA S. Among the carbapenems. pneumoniae multi-antibiotic resistant Penicillins Cephalosporins Aztreonam Abbreviations: ESBL. methicillin-resistant S. The available well-designed studies indicate that this practice results in a modest increase in therapeutic advantage and possibly a decrease in toxicity. among others. Table 7 lists the major serious adverse reactions of the commonly used antibiotics. aureus. Unasyn). imipenem is not recommended because of the risk of seizures. GISA. antipseudomonal penicillins (eg. The antibiotics that must be avoided in pregnancy include the antimycobacterial agent. 32nd edition. because of permanent intrinsic dental staining. epidermidis VRMRSE Streptococcus pneumoniae penicillin intermediate or resistant S. Once-daily dosing for the aminoglycosides as a means of reducing their ototoxicity and nephrotoxicity recently has been evaluated in a systematic review .R. Inc. epidermidis.26 T. gastrointestinal intolerance of the erythromycins. piperacillin). L.R. the Streptococcus milleri group associated with odontogenic infections is highly sensitive to the penicillins. Moellering RC Jr. Caution is advised in patients with limited volumes of fluid distribution. however. Meropenem is an acceptable alternative. Adverse reactions The adverse reactions and toxicities of the antibiotics commonly used in head and neck infections are generally mild and uncommon. nephrotoxicity and ototoxicity of the aminoglycosides. Augmentin. The clinician especially should note allergic reactions to the penicillins and cephalosporins. Fortunately for oral and maxillofacial surgeons. and the fluoroquinolones. The pharmacokinetics of the clinically available antibiotics have been determined during drug development. Table 8 lists the pregnancy risk categories of selected antibiotics. because of chondrotoxicity in growing cartilage. and the antiparasitic agent. aureus VISA or GISA Staphylococcus epidermidis MRSE S. It is incumbent on the clinician to prescribe antibiotics within the accepted ranges for dose and interval. MRSE. . VRMRSE. extended-spectrum b-lactamase. Sande MA. glycopeptide-intermediate S.. The Sanford guide to antimicrobial therapy. for which the risk clearly outweighs the benefit. whereas the endocarditisassociated strains are less so. epidermidis. thalidomide.
2002. and the serum level of the estrogen is supported by enterohepatic recirculation. the gut flora breaks the estrogenglucuronide bond. In this process. It is important to note that antibiotics do not interfere with injectable or implantable contraceptives. Antibiotic interference with the effectiveness of oral contraceptive pills remains a controversial topic. life-threatening or fatal cardiac dysrhythmias. Enzymes within this system include CYP3A4. Currently. then the conjugated estrogen is not broken down. b Imipenem is avoided in meningitis because of seizure potential. 32nd edition. Inc. which involves the cytochrome P450 system. The cytochrome P450 system is a complex set of drug-metabolizing enzymes that is responsible for the breakdown of many classes of drugs.R. c Does not reach adequate cerebrospinal fluid levels for streptococci. and the antiviral protease inhibitors is less strong. Meropenem is preferred. In turn. which results in breakthrough menstrual bleeding or ovulation and unwanted pregnancy. The serum estrogen level falls. The evidence that implicates ampicillin. Sande MA. dapsone. . The metabolism of one or the other may be either increased or decreased as a result. A possible mechanism for this interaction stems from efforts to decrease the adverse effects. If an antibiotic kills enough of the gut flora. such as thromboembolism and activation of uterine and breast carcinomas associated with older contraceptive formulations that contained higher estrogen doses. The adverse affect is usually caused by an increased effect of the drug whose metabolism is inhibited. thus supporting the serum estrogen level. Therapeutic levels not achieved Data from Gilbert DN. trimethoprim/sulfamethoxazole.. but in some of the most serious cases. oral contraceptive preparations have minimally effective estrogen doses. and the estrogen-glucuronide complex stays in the intestine until it is excreted.R. These and other selected antibiotic drug interactions are listed in Table 9. have occurred. The most significant interactions involving the cytochrome P450 system are included in Table 9. a Levels effective for P. The Sanford guide to antimicrobial therapy. the liver conjugates absorbed estrogen with glucuronide. Drugs that share this metabolic pathway may interact. which allows the pure estrogen molecule to be reabsorbed by the gut. Flynn. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 6 Selected antibiotics and the blood-brain barrier Cerebrospinal fluid Therapeutic levels achieved Antibiotic Penicillins ampicillin nafcillin penicillin G. aeruginosa and coliforms may not be reached. and the estrogen-glucuronide complex is excreted in the bile. e High doses are needed for resistant streptococci. and CYP2D6. d Not adequately effective against Neisseria species and coliforms. The only antibiotic that has been shown conclusively to interfere with oral contraception is rifampin. high dose ticarcillina piperacillina Cephalosporins ceftazidime cefuroxime ceftriaxone Carbapenem meropenemb Fluoroquinolones levofloxacin ciprofloxacinc Other antibiotics metronidazole trimethoprim/ sulfamethoxazoled vancomycine Antifungal drugs fluconazole flucytosine Antiviral drugs acyclovir foscarnet ganciclovir zidovudine Cephalosporins cefazolin cephalexin Aminoglycosides Macrolides erythromycin clarithromycin azithromycin Clindamycin Antifungal drugs amphotericin itraconazole Antiviral drugs saquinavir zidovudine 27 Antibiotic drug interactions Two important categories of antibiotic drug interaction are interference with the effectiveness of oral contraceptives and interference with the metabolism of drugs.T. Hyde Park (VT): Antimicrobial Therapy. L. Only oral contraceptives are affected . amoxicillin. CYP2C19. such as ventricular fibrillation and torsade des pointes. Moellering RC Jr.
Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Adverse reactions Local. Cephalexin. The Sanford guide to antimicrobial therapy.R. . Moellering RC Jr. L. Flynn. Impenem Meropenem tobramycin cefazolin Cefuroxime Cefoxitin Cefotaxime Cefaclor T.28 Table 7 Major adverse reactions of selected antibiotics Ampicillin. Sande MA. 32nd edition. creatinine Headache Seizures Hypotension Ototoxicity Vestibular dysfunction Alcohol interaction ‘‘Red man’’ flushing Drug interactions Pregnancy risk C or D + + Data from Gilbert DN. phlebitis Hypersensitivity Rash Photosensitivity Anaphylaxis Serum sickness Anemia Nausea.R. vomiting Diarrhea Antibiotic-associated colitis (AAC) Renal: z BUN. Inc. Penicillin G amoxicillin F and V clavulanate + + + + + + + + + + + + + + + Ticarcillin F clavulanate Gentamicin. Hyde Park (VT): Antimicrobial Therapy.. 2002.
L. vomiting Diarrhea AAC Renal: z BUN.R. phlebitis Hypersensitivity Rash Photosensitivity Anaphylaxis Serum sickness Anemia Nausea.R. doxycycline Linezolid Telithromycin + + + + + + + + + + + + + + + + + + + + + + + + 29 . Flynn.T. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 7 (continued ) Erythromycin Local. azithromycin Clindamycin Metronidazole Ciprofloxacin Moxifloxacin Vancomycin + + + Tetracycline. creatinine Headache Seizures Hypotension Ototoxicity Vestibular dysfunction Alcohol interaction ‘‘Red man’’ flushing Drug interactions Pregnancy risk C or D Clarithromycin.
D = Evidence of human risk. Hyde Park (VT): Antimicrobial Therapy. Sande MA. The costs of oral antibiotic therapy can be compared based on the cost for a standard prescription for the antibiotics of interest. these costs are conservatively estimated at . Cost Although clinical effectiveness and reduction of the morbidity of infection and treatment are of paramount concern in the management of head and neck infections. Flynn. B = Animal studies no risk.. because there is no additional cost of administration.R. espe- cially by the intravenous route. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 8 Pregnancy risk categories of selected antibiotics Antibiotic Penicillins penicillin G and V ampicillin amoxicillin amoxicillin/clavulanate ticarcillin/clavulanate Cephalosporins cephalexin cefazolin cefaclor cefuroxime cefoxitin cefotaxime Carbapenems imipenem meropenem Macrolides erythromycin clarithromycin azithromycin Antianaerobic clindamycin metronidazole Fluoroquinolones ciprofloxacin moxifloxacin Aminoglycosides gentamicin tobramycin Other vancomycin tetracyclines doxycycline linezolid telithromycin Pregnancy risk category B B B B B B B B B B B C B B C B B B C C D D C D D C B Spontaneous abortions in rabbits Fetal toxicity in rodents and monkeys Ototoxicity in human fetuses Ototoxicity in human fetuses Potential ototoxicity in human fetuses Intrinsic dental staining Intrinsic dental staining Fetal toxicity in rodents Spontaneous abortions in monkeys Pregnancy risk Fetal defects in mice and monkeys Data from Gilbert DN. A = Studies in pregnancy. but benefit of use may outweigh risk. L.R. Table 11 compares the cost of intravenous antibiotics. professional labor. Moellering RC Jr. as there is with parenteral antibiotics. Table 10 compares the retail cost of a 1-week prescription of the antibiotics listed.In Table 11. cost is a factor that should be considered when other factors do not predominate. 2002. Each dose requires sterile intravenous administration supplies. C = Animal studies show toxicity. and hospital sterile processing and drug error prevention systems. no risk.30 T. but human studies inadequate or animal toxicity. The cost of administration assumes great importance. Inc. and human studies inadequate. X = Risk outweighs benefit. 32nd edition. but human studies no risk. The Sanford guide to antimicrobial therapy. but benefits may outweigh risk. The penicillin V cost ratio is calculated by dividing the retail cost of the standard 1-week prescription for the given antibiotic by that of penicillin V.
b Antibiotic Erythromycin. clarithromycin. tetracyclines Clindamycin Digoxin Erythromycin. clarithromycin. ketoconazole. hypotension Antibiotic inhibits cytochrome P450 metabolism of second drug Ataxia. itraconazole Lovastatin. oral midazolam Erythromycin. clarithromycin. ketoconazole. dysrhythmias Mechanism 31 Erythromycin. prednisone Erythromycin. ketoconazole. vertigo. ketoconazole. ketoconazole not implicated Dysrythmias (torsades) Antibiotic inhibits cytochrome P450 metabolism of second drug z Respiratory depression Antibiotic inhibits cytochrome P450 metabolism of second drug. itraconazole Bromocriptine Erythromycin. ketoconazole. disturbances. tachycardia. ketoconazole. L. itraconazole Felodipine. clarithromycin. clarithromycin. Antibiotic inhibits edema cytochrome P450 metabolism of second drug z Immunosuppression Antibiotic inhibits cytochrome P450 metabolism of second drug Muscle pain. itraconazole Carbamazepine Erythromycin. itraconazole Methylprednisolone.R. Flynn. ketoconazole. ketoconazole. itraconazole Disopyramide Erythromycin Erythromycin. itraconazole Triazolam. clarithromycin.T. metronidazole Warfarin Anisindione Antibiotic inhibits cytochrome P450 metabolism of second drug. clarithromycin. itraconazole Second drug Theophylline Adverse effects Seizures. visual Eubacterium lentum. clarithromycin. clarithromycin. ketoconazole not implicated z CNS effects. ketoconazole. itraconazole Cisapride Erythromycin. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 9 Selected antibiotic interactions with other drugsa. itraconazole Alfentanil Erythromycin. possibly other -statins Erythromycin. ketoconazole. possibly other calcium channel blockers Erythromycin. rhabdomyolysis Antibiotic inhibits cytochrome P450 metabolism of second drug z Sedative depth and duration Antibiotic inhibits cytochrome P450 metabolism of second drug Dysrhythmias Antibiotic inhibits cytochrome P450 metabolism of second drug # Antibiotic effect Mutual antagonism Digitalis toxicity. which metabolizes hypersalivation digoxin in the gut z Anticoagulation Antibiotic interferes with metabolism of the second drug (continued on next page) . clarithromycin. ketoconazole. drowsiness Antibiotic inhibits cytochrome P450 metabolism of second drug z Immunosuppression Antibiotic inhibits and nephrotoxicity cytochrome P450 metabolism of second drug Hypotension.R. Antibiotic kills dysrhythmias. clarithromycin. clarithromycin. itraconazole Cyclosporine Erythromycin.
nausea Metronidazole Metronidazole. ritonavir Flushing. aminoglycosides.R. cefoperazone. anisindione cefotetan. ataxia. aminoglycosides Metronidazole. L. tetracyclines. possibly caused by hyperuricemia in patients taking allopurinol Additive or potentiating effect Thrombocytopenia Additive effect (continued on next page) Tetracycline. rifampin Erythromycin # Antibiotic effect Estrogen. erythromycin.and progestinContraceptive failure containing oral contraceptives Ampicillin. Warfarin. fluoroquinolones Divalent and trivalent cations (dairy. palpitations.R.32 Table 9 (continued ) Antibiotic T. which antagonizes the second drug. causing accumulation of acetaldehyde. bacitracin Neuromuscular blocking agents z Depth and duration of paralysis Clindamycin Penicillins. cephalosporins Alcohol. sulfonamides. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Second drug Adverse effects z Anticoagulation Mechanism Antibiotic kills gut flora that synthesize vitamin K. headache. metronidazole. antacids. poor vitamin K intake a factor Antibiotic inhibits acetaldehyde dehydrogenase. cefamandole. amoxicillin Allopurinol Rash Cephalosporins Trimethoprim/sulfamethoxazole Vancomycin Aminoglycosides Thiazide diuretics Aminoglycosides z Nephrotoxicity Purpura. rifampin is the only antibiotic in which this has been clinically proven Unknown. didanosine is formulated with calcium carbonate and magnesium hydroxide buffers Additive effect caused by inherent minor neuromuscular blocking effect of the antibiotic. Flynn. tetracyclines. ritonavir preparations contain alcohol Antibiotic inhibits lithium excretion by kidney. seen with clindamycin in the presence of low pseudocholinesterase levels and abnormal liver function tests Mutual antagonism Interference with enterohepatic recirculation of estrogen caused by killing of gut flora. tetracyclines Disulfiram Lithium Acute toxic psychosis Lithium toxicity: confusion. clarithromycin. vitamins) didanosine # Absorption of antibiotic Clindamycin. tetracycline interaction not well established Second drug interferes with absorption of antibiotic. bleeding in elderly patients z Renal toxicity . kidney damage Tetracyclines. cephalosporins.
1 week’s intravenous therapy of penicillin G plus metronidazole costs $690. sulfonamides. itraconazole Sulfonamides Second drug Oral hypoglycemic agents Adverse effects Hypoglycemia Mechanism Antibiotic displaces second drug from plasma proteins Interference with phenytoin metabolism 33 Phenytoin z Serum level of phenytoin. Even this small additional cost can make an infrequently administered but more expensive antibiotic more economical than a cheaper. Metronidazole crosses the blood-brain barrier well. loratidine. because clindamycin does not cross the blood-brain barrier and penicillin does so only to a limited extent. chloramphenicol. alfentanil. with possible toxic effects Protease inhibitors # Levels of second drug Delavirdine (Rescriptor) Cisapride. fentanyl. New antibiotics of interest to oral and maxillofacial surgeons New fluoroquinolones Moxifloxacin (Avelox) and gemifloxacin are two new fluoroquinolones whose spectrum includes . protease inhibitors.R.00 per dose. Oral and maxillofacial surgery knowledge update 2001. amprenavir. itraconazole Ciprofloxacin. clarithromycin. for example. On the other hand. lidocaine. with permission. sulfonamides. Videx) Foscarnet (Foscavir) Metronidazole Ciprofloxacin z Risk of peripheral neuropathy z Risk of seizures Antibiotic displaces methotrexate from plasma proteins Serious interaction: avoid using the drugs in bold print Ritonavir has high affinity for various isoenzymes in the cytochrome P450 system and has the most frequent and severe drug interactions among the protease inhibitors Warfarin reaction is only with ritonavir Antibiotic enhances cytochrome P450 metabolism of second drug Antibiotic inhibits cytochrome P450 metabolism of second drug Additive effect Additive effect From Flynn TR. delirium z Methotrexate concentration Methotrexate Protease inhibitors (ritonavir. a reduction of 46%. whereas 1 week’s treatment with clindamycin costs only $375. 2001. saquinavir. more frequently dosed antibiotic. Flynn. Update on the antibiotic therapy of oral and maxillofacial infections. anticonvulsants. and others) Hydrocodone.R.T. indinavir. nelfinavir. b This list of antibiotic-drug interactions is only partial and selected according to the interests of oral and maxillofacial surgeons. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 9 (continued ) Antibiotic Fluoroquinolones. The reader is referred to appropriate sources on the subject. fluconazole. chloramphenicol. ketoconazole. Table 11 also illustrates the markedly increased cost of combined antibiotic therapy as compared to monotherapy. editor. An example of this effect can be found by comparing the cost ratio of penicillin G (analogous to the penicillin V cost ratio) with cefazolin. In: Piecuch JF. confusion. with possible toxic effects Didanosine (ddl. $4. Benzodiazepines b-blockers Calcium channel blockers Cisapride Corticosteroids -statin type antihyperlipidemics Warfarin Codeine. fluconazole. morphine. For example. warfarin z Levels of second drug. Drug prescribers remain responsible to ascertain the complete drug interactions of any medications they may prescribe. contraceptives z Levels of second drug. L. the combination approach may be advantageous in an infection that threatens the brain. amiodarone. Rosemont (IL): American Association of Oral and Maxillofacial Surgeons. a Interactions among the various anti-HIV antibiotics are frequent and complex.
It is effective against virtually all gram-positive pathogens but not against the gramnegative oral anaerobes.99 $70. including S. Ketolides Telithromycin (Ketek) is the first representative of this new class.44 $1. mycoplasma.24 $12.49 $63.59 $9.84 $16.36 $0. the viridans streptococci. RPh.11 $0.07 $3.00 1.14 $0.41 7.39 $7.07 20.30 $0. They are also effective against sinus pathogens.99 $13.99 $97.66 $1.86 $118.59 $199.76 $0.00 $1. Inc. d Retail cost/1 week = retail price charged for a 1-week prescription at a large pharmacy chain in the Boston region.59 $13.52 Retail cost for 1 weekd $9.93 $10.99 $187.52 $2. a Augmentin = amoxicillin plus clavulanic acid. Their broad spectrum is a relative disadvantage when the target is a fairly small range of bacteria. Oxazolidinones Linezolid (Zyvox) is the prototype of this new class of antibiotics. 31st edition.15 $4.51 7.65 $4.57 $6. 2001.75 $0.29 $12.88 $0.72 $0.31 $12. b Keftab = cephalexin hydrocloride in tablet form (Dista).69 $24. Chlamy- . From Gilbert DN.27 $10.52 $7.and vancomycin-resistant staphylococci and enterococci indicates that it should be reserved for these highly resistant organisms .67 2. Its spectrum includes the pathogens against which the macrolides have been historically effective.15 $0. H.95 $9. Moellering RC Jr. These new fluoroquinolones probably should be reserved for situations in which a narrower spectrum alternative antibiotic is not available. Hyde Park (VT): Antimicrobial Therapy. Sande MA.64 $4.84 1. c Penicillin cost ratio = retail cost of antibiotic for 1 week retail cost of penicillin V for 1 week.44 $2.00 18.99 $71.02 $11. which is related to the macrolides.00 $0.31 $3.30 $8.29 $54.38 Cost for 24 hours $0.69 $80.89 $104.00 1.28 $12.77 1. Enterobacteriaceae.99 $60.08) Other Trimethoprim/sulfamethoprim Ciprofloxacin Doxycycline Vancomycin Usual doses and intervals are for moderate infections.21 6. fragilis.59 $31.22 $0. staphylococci.39 $3.44 $1. and are not to be considered prescriptive.63 1.07 1.75 $3.43 $4. oral anaerobes. and B.39 1.98 $1.13 5. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Usual dose (mg) 500 500 500 875 500 500 500 500 500 500 500 333 250 500 500 250 150 300 300 500 160/800 500 100 125 Usual interval (h) 6 8 8 12 6 6 6 6 8 8 6 6 6 24 12 24 6 6 6 6 12 12 12 6 Pharmacy Cost ’01 * * $0. Its effectiveness against methicillin.R.51 9. influenzae.R.08 $22.92 $7.88 $2.07 3.17 8.36 $0.59 $26.89 $104.16 $21.34 Table 10 Oral antibiotic costs Antibiotic T.02 7.99 $77.49 11.39 10.56 $0.35 6.89 $16. L.99 Penicillin cost ratioc 1.49 10. pneumoniae. Flynn. The Sanford guide to antimicrobial therapy 2001.08 $5. and actinomyces.77 2.14 $6.96 $4.82 Penicillins Penicillin V Amoxicillin Augmentina Augmentin Dicloxacillin Cephalosporins (generation) Cephalexin caps (1st) Keftabs (1st)b Cephradine (1st) Cefuroxime (2nd) Cefaclor (2nd) Erythromycins Erythromycin base Erythromycin stearate Erythromycin estolate Dirythromycin (Dynabec) Clarithromycin (Biaxin) Azithromycin (Zithromax) Anti-anaerobic Clindamycin (generic) Clindamycin (2 T generic) Clindamycin (Cleocin) Metronidazole (250 mg = $0.29 $13. Courtesy of Chris Gonzalez.
70 $7.28 $21.33 $1.00 3.68 $68.43 $15.88 $19. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 11 Intravenous antibiotic costs Antibiotic Usual doseb Usual interval (hour)b 6 6 6 6 4 4 8 12 8 8 8 24 8 6 6 24 6 12 8 6 12 6 12 Pharmacy cost ’00 $1.91 $137. especially pneumonia [26.45 $42. Empiric antibiotics of choice for head and neck infections Odontogenic infections Empiric antibiotics are administered before culture and sensitivity test results are available.00 $199.24 $73.93 2.18 $62.74 $11.R.5 g Vancomycin 1.32 $1.45 $40.03 $21.64 0.06 $806. d Cipro IV is for NPO patients only because of excellent oral absorption.24 $571.80 $36.64 $10.20 $53.97 $30.28 $16. From Gilbert DN.9 g Metronidazole 0.T. a Penicillin cost ratio = 24-hour cost of antibiotic/24-hour cost of penicillin G.84 $287.92 $732.57 2.40 $123.08 2.08 1.96 6.00 Pharmacy cost ’01 $1.51 4.37 $960.27].35 $44. 31st edition.77 3.32 $81.1 g Cephalosporins (generation) Cefazolin (1st) 1g Cefotetan (2nd) 1g Cefuroxime (2nd) 1.14 $13. Pristinamycins Quinupristin/dalfopristin (Synercid).5 g Other Doxycycline 0.18 $2.68 $516.16 $23. Hyde Park (VT): Antimicrobial Therapy. including odontogenic infections. c Only the brand name price is listed in the reference.00 Total cost 24 hours $21.80 $637.40 $373.00 labor cost.97 $30.64 $77. The Sanford guide to antimicrobial therapy 2001.45 $309. Its most frequent use probably is in respiratory tract infections. L.07 $16. dia pneumoniae.00 for infusion materials and $3.31 $14.34 2.60 $13.56 $13.38 $28. Price is selected from the lowest available average wholesale price.90 $11. Flynn. and Legionella pneumophila.60 $255.70 $31. per dose.36 $16. Sande MA.44 $8.20 Penicillins Penicillin G 2 mu Ampicillin 1g Unasyn 2g Oxacillin 1g Ticarcillin 3g Timentin 3.12 $41.84 $375.08 $343.1 g Trimethoprim-sulfa 800 mg Ciprofloxacind 400 mg Total cost of therapy includes $1.45 $5.18 $16.5 g Cefotaxime (3rd) 2g Ceftazidime (3rd) 2g Ceftriaxone (3rd) 1g Monobactam Aztreonam 1g Carbapenem Imipenem-cilastatin 0. 2001.96 $148.41 0.20 $17.88 $15.83 1.84 3.72 4.91 5. a combination of two pristinamycin antibiotics.47 2.0 g Anti-anaerobic Clindamycin 0.28 $108.00 1.48 $541. Its use generally has been reserved for infections caused by these organisms.90 $218.00 $28.40 $1. b Usual doses and intervals are for moderate infections and are not to be considered prescriptive.98 $681.58 $115.58 $13.60 $13.45 5.42 $30. .14 $97.16 $16. Inc.28 4.16 $28. is especially effective against vancomycin-resistant staphylococci.80 $26.96 $756.40 $91.31 1.47 1.26 $440.76 $476.12 $53.68 $12.32 $22.92 $15. Table 12 lists the empiric antibiotics of choice for selected types of head and neck infections.00 $24.00 Total cost for 7 days $148.00 35 Penicillin G cost ratioa 1.44 $49.52 $114.5 g Penicillin allergy Erythromycinc 1g Azithromycin 0.42 $30.20 $1. Moellering RC Jr.34 $4.56 $104.5 g Vancomycin 0.R.52 3. specific antibiotic therapy is selected based on culture and sensitivity results.32 $23.00 $16.93 $21.80 $15.
neutropenia. Patients with severe pain or fever may need antibiotic therapy sooner. Because of their ineffectiveness against the oral anaerobes.R. such as Fusobacterium. pneumoniae is more than 30%. It is increasingly apparent from case reports. On the other hand. Molecular methods ultimately may become the most rapid and reliable method for identifying Actinomyces . Deferoxamine (Desferal) is an iron-chelating agent used in Alzheimer’s disease. Amphotericin B and surgery are indicated. aureus is found in only approximately 4% of cases of acute rhinosinusitis . Sinus infections Acute rhinosinusitis of odontogenic origin is characterized by the same flora as other odontogenic infections. This finding suggests a correlation between infection severity and penicillin resistance and is the basis for the recommendation of clindamycin as the empiric antibiotic of choice in odontogenic infections serious enough to require hospitalization . along with discontinuation of deferoxamine. pneumoniae. failure of swelling. if applicable.R. which causes surface lesions in non-immunocompromised patients . aspergillosis and mucormycosis. the flora becomes more anaerobic. influenzae.36 T. Antibiotic treatment should be reserved for patients who already have been treated for 7 days with only decongestants and analgesics and who have maxillary or facial pain or purulent nasal discharge. surgery was repeated. the cephalosporins remain secondline choices. If inadequate drainage was found on the postoperative CT scan. especially those in the first generation. All of the patients with therapeutic penicillin failure (8 of 31 cases initially treated with penicillin) subsequently yielded at least one penicillin-resistant strain when culture and sensitivity test results became available. One also may suspect skin and soil pathogens in traumatic osteomyelitis and salmonella in sickle-cell osteomyelitis. penicillin resistance has not yet been shown to be a significant problem in outpatient odontogenic infections [11 – 14]. and white blood cell count to decline after at least 48 hours of intravenous penicillin. which tend to cause sinusitis. amoxicillin and clavulanic acid or a secondor third-generation cephalosporin is prescribed for two weeks . L. Actinomyces are another prominent pathogen in chronic osteomyelitis. usually with otorhinolaryngology consultation. H. Moraxella catarrhalis. temperature. Prevotella. however. and corrective surgery. Fungal infection of the sinuses should be suspected and treated urgently with antibiotics and surgery in patients with acute rhinosinusitis who have diabetes mellitus with acute ketoacidosis. and streptococci. and candidiasis. Osteomyelitis of the jaw The microbiology of osteomyelitis of the jaws has not been reported specifically in a large case series. Because the oral anaerobic gram-negative rods are fairly resistant to most cephalosporins. a recent systematic literature review indicates that penicillin or amoxicillin alone is as effective as the other broader spectrum and more expensive antibiotics . Penicillin V remains the empiric antibiotic of choice for outpatient odontogenic infections. Flynn. On the other hand. Antibiotics alone are not usually effective in these cases. Non-odontogenic acute rhinosinusitis is frequently caused by S. including B. Oral penicillins plus probenecid can be used for long-term outpatient therapy. and a postoperative CT scan that demonstrated adequate surgical drainage. except that not all of the species found in the periapical infection survive in the sinus location . The major fungal infections of concern to oral and maxillofacial surgeons are histoplasmosis and blastomycosis. Mucormycosis has been found in patients who are undergoing simultaneous deferoxamine treatment and hemodialysis. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 In a prospective case series of 34 cases of odontogenic infection. S. and culture and microscopic examination may be required to identify this organism. and Porphyromonas. Long courses of the antibiotics effective against the Actinomyces are required (see Table 4). and hospitalization may be required in these cases. the macrolides are no longer considered among the empiric antibiotics of choice for odontogenic infections. Flynn et al reported therapeutic failure of penicillin in 26% of cases using the following criteria for failure: allergic or toxic reaction (no cases). Fungal infections Various fungi cause a wide spectrum of infectious manifestations in the head and neck. which may cause granulomatous oral lesions. is indicated. or previous treatment with deferoxamine. If antibiotics have been used in the previous month or if the local incidence of penicillin-resistant S. In chronic rhinosinusitis. fragilis and the peptostreptococci. Probenecid inhibits the renal excretion of penicillin and increases the blood level obtained by the oral route. that the usual odontogenic pathogens are the most frequent cause. An excellent review of the topic can be found in a recent chapter by Bergman .
blastomycosis. and use of molecular methods. 32nd edition. Flynn.2002. In surface candidiasis in a patient with a healthy immune system. Hyde Park (VT): Antimicrobial Therapy Inc. and may cause disseminated and invasive disease in immunocompromised persons.R. clotrimazole is a better-tasting yet economical alternative to nystatin. fungal infections are treated with the azole-type antifungal agents for less severe cases and amphotericin B for disseminated and severe disease. Moellering RC Jr. such as polymerase chain reaction.. L. Histoplasmosis.T. histologic examination with special stains. The Sanford guide to antimicrobial therapy. . In general.R. and mucormycosis are diagnosed by surgical sampling for culture. non-AIDS Oral. AIDS Fluconazole or itraconazole Nystatin or clotrimazole Fluconazole or itraconazole Amphotericin B Data from Gilbert DN. Sande MA. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 Table 12 Empiric antibiotics of choice for head and neck infections Type of infection Odontogenic infections Outpatient Empiric antibiotic of choice 37 Penicillin allergy Inpatient Penicillin allergy Penicillin Clindamycin Cephalexin (or other first-generation cephalosporin) Clindamycin Cephalexin (only if nonanaphylactoid penicillin reaction) Clindamycin Ampicillin + metronidazole Ampicillin + sulbactam Clindamycin Moxifloxacin Cefotaxime (only if nonanaphylactoid penicillin reaction) Amoxicillin Amoxicillin/clavulanate Cefuroxime Moxifloxacin (over 18 years of age) Clarithromycin or azithromycin Telithromycin Moxifloxacin (over 18 years of age) Antibiotics not effective: otolaryngologic consultation Imipenem or meropenem Ticarcillin or piperacillin Ceftazidime + vancomycin Cefepime Amphotericin B Clindamycin Ampicillin + metronidazole Ampicillin + sulbactam Clindamycin Moxifloxacin Itraconazole Fluconazole Amphotericin B (systemic or disseminated) Rhinosinusitis Acute Penicillin allergy Chronic Intubated Fungal Osteomyelitis of the jaw Penicillin allergy Histoplasmosis and blastomycosis Candidiasis Oral.
Microbiological profile of telithromycin.  Flynn TR. Flynn. McGowan P. Once-daily dosing of aminoglycoside antibiotics. Bacteriology of dentoalveolar abscesses in patients who have received empirical antibiotic therapy.174:443 – 9. Clindamycin.R. the first ketolide antimicrobial. 59:739 – 48. Roum Arch Microbiol Immunol 1999. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000. J Oral Maxillofac Surg 1988. Ebersole JL. J California Dental Assoc 1999. Fisman DN.46:1065 – 70. Paterson SA.7(Suppl 3):2 – 10.25:637 – 47.130:236 – 51. Lewis MA.67:608 – 10. Cochrane Library 2000.. 243 – 78. Br Dent J 1993. 2002. Kasten MJ.  Neu HC. and protozoal infections of the maxillofacial region.105:173 – 81.  Fazakerley MW. Indresano AT. Drug allergy: fact or fiction? Int J Clin Pract 1998.58:57 – 63. Clin Infect Dis Suppl 1996. Emerging trends in antimicrobial resistance in surgical infections: a review. 2001. Microbiology of common infections in the upper respiratory tract. Marchese A. 40:891 – 4. Halpern / Oral Maxillofacial Surg Clin N Am 15 (2003) 17–38 spective double-blind evaluation of penicillin versus clindamycin in the treatment of odontogenic infections. Emergence of high rates of antimicrobial resistance among viridans group streptococci in the United States. et al. In: Topazian RG.38 T.22:401 – 4. Morris-Stiff GJ. MacFarlane TW. J Oral Maxillofac Surg 2001. Kaye KM. p. Antimicrobial susceptibility of some streptococci strains of anginosus group isolated from oral and maxillofacial infections. Drugs 2002. Clin Microbiol Infect 2001.  Doern GV. Warrington RJ. Adverse drug interactions in dental practice: interactions involving antibiotics. Felmingham D.    References  Flynn TR.62:425 – 41. The effect of amoxycillin versus penicillin V in the treatment of acutely abscessed primary teeth. Hoffman MJ. Adverse reaction to amoxicillin: a case report. In: Piecuch JF. Antimicrob Agents Chemother 1996. 32nd edition. Hardy P. Bergman SA. Goldberg MH. Past administration of b-lactam antibiotics and increase in the emergence of b-lactamase-producing bacteria in patients with orofacial odontogenic infections. 2000. and chloramphenicol. L. The Sanford guide to antimicrobial therapy. Hersh EV. An epidemiologic and anatomic survey of odontogenic infections. Bancescu G. A comparative study of cephradine. Gorbach SL. 573:7 – 18. Milligan SG.14:475 – 87. Predicting length of hospital stay and penicillin failure in severe odontogenic infections. metronidazole.74:825 – 33.49:976 – 80. Linden PK. and even geographic. Dumitriu S. Oral and maxillofacial surgery knowledge update 2001.3:1 – 51. Aguilar C. 4th edition.B.174:359 – 63.89:186 – 92. et al. The value of testing for penicillin allergy in an inpatient population: analysis of the subsequent patient management. Lee KR. Allergy Asthma Proc 2000. editors. Oral and maxillofacial infections. Antibiotics for acute maxillary sinusitis. Clin Microbiol Infect 2001. p. Saunders Co. Mayo Clin Proc 1999. increasing antibiotic resistance. Ruoff KL. Nakagawa K. et al. Int J Oral Maxillofac Surg 1999. Rosemont (IL): American Association of Oral and Maxillofacial Surgeons. editor. Microbiology of periapical abscesses and associated maxillary sinusitis. Treatment options for vancomycin-resistant enterococcal infections. Gher Jr ME. Periodontology 2000. Craig TJ.175:169 – 74. Hupp JR. Cappelli D. Fungal.  Gilmore WC. Mende C. Gilbert DN.R. Update on the antibiotic therapy of oral and maxillofacial infections. and best practices in antibiotic usage.  Haug RH. Adamo AK. McPhillips S. The oxazolidinones as a new family of antimicrobial agent. Much more research is necessary in this field to solve the current problems with the need for more timely culture and sensitivity results. Curzon ME. Part II. pharmacologic.7(Suppl 4):66 – 74. Brook I. amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar infection. Br Dent J 1993.  Storoe W. et al. Karasawa T. Summary Antibiotic selection remains as much of an art as it is a science.. 23 – 50.1:S51 – 3.  Kulekei G. Pediatr Dent 2000. Kocak H. Prim Care 1998. Br Dent J 1993. Williams Jr JW. J Am Dent Assoc 1999. Carmichael F. viral.  Molinari JA. It requires the integration of many factors that are host specific. Wiltz M. A pro-                . A randomised trial of co-amoxiclav (Augmentin) versus penicillin V in the treatment of acute dentoalveolar abscess.27:386 – 92. Haug RH. Moellering Jr RC. Lillich TT. Schito GC. Martin MV.52:20 – 1. et al. Infect Dis Clin North Am 2001. Acute-phase reactants in infections and inflammatory diseases. Postgrad Med 1999. Sande MA. Frazier EH. Bowrey DJ.28(Suppl 1):48. Ferraro MJ. Common allergic and allergic-like reactions to mediations: when the cure becomes the curse. J Periodontol 1996.23:19 – 49.  Brook I.  Kuriyama T. The changing face of odontogenic infections. J Oral Maxillofac Surg 1991. Eur J Surg Suppl 1994. Skaug N. Philadelphia: W. Antibiotic resistance and maxillofacial pathogens: emerging treatment issues. Makela M. Hyde Park (VT): Antimicrobial Therapy Inc. Inane D. DeFonseca MA. Jacobus NV. Brueggemann AB. et al.21:297 – 9.