Acs0815 Antibiotics


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Acs0815 Antibiotics

  1. 1. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 1 15 ANTIBIOTICS Nicolas V Christou, M.D. . Antibiotic Therapy in Surgical Patients Several important advances in antimicrobial therapy have been National Committee for Clinical Laboratory Standards made since the early 1980s. Among these advances are (1) im- (NCCLS)1 for in vitro susceptibility testing. Commercially avail- proved understanding of the microbiologic spectrum of so-called able paper disks containing specific amounts of antimicrobial optimal therapy, (2) better application of pharmacokinetic princi- agents are placed on Mueller-Hinton agar plates that contain a ples to drug administration, (3) the development of several new standard bacterial inoculum. A zone of inhibition of bacterial classes of antibiotics, and (4) greater insight into the interplay growth develops around each active antibiotic after overnight among host resistance factors, microorganisms, and chemotherapy. incubation. The size of the zone determines the organism’s sus- ceptibility or resistance; prior studies have correlated zone sizes with MICs obtained through dilution tests. Arbitrary zone-size General Principles of Antimicrobial Therapy break points for susceptibility have been established by clinical and laboratory investigators on the basis of such additional factors as EMPIRICAL THERAPY achievable serum levels, degree of protein binding, and toxicity. Even with the most rapid bacteriologic tests currently available, The broth dilution method exposes an inoculum of bacteria to it may not be possible to identify a pathogen in less than 24 hours, various concentrations of an antimicrobial agent during incuba- and antimicrobial sensitivities can rarely be obtained in less than tion. The MIC of an agent that inhibits growth can be deter- 48 to 72 hours. In seriously ill patients, treatment cannot be mined, and this value can be correlated with blood, urine, or delayed for 2 to 3 days until these data become available. If ther- other body fluid levels of the antimicrobial agent. Moreover, apy is to be successful, it must be started as soon as a life-threat- those tubes that show inhibition of growth can be subcultured to ening infection is diagnosed or, in some patients, as soon as such an antimicrobial-free medium, and the minimal bactericidal con- an infection is suspected. Which antimicrobial agents are to be centration (MBC) can be determined. Unfortunately, this test is used depends on the suspected site of infection and on the organ- not well standardized at present, and its reproducibility is poor isms that are commonly pathogenic at this site.Therapy is initiat- when it is subjected to intralaboratory and interlaboratory com- ed with an agent or combination of agents whose action is broad parisons.2 enough to cover all the suspected microbial pathogens.The appli- The agar dilution method works in much the same way as the cation of such broad-spectrum antibiotic therapy in the absence broth dilution method, except that the former employs agar of microbiologic confirmation is termed empirical therapy. plates that contain various dilutions of antimicrobial agents, and To make a rational decision regarding empirical therapy, the as many as 36 organisms can be efficiently inoculated on each surgeon must be familiar with the organisms that are likely to be plate by means of a replicator device. The MIC is determined by encountered when a particular infection (e.g., an intra-abdominal reading inhibition of colony growth on the agar surface. Agar abscess) is suspected. Selection of the agent or agents is based on dilution has the advantage of producing MIC data efficiently in a the history, the physical examination, where the infection was laboratory that performs large numbers of tests daily. likely to have been acquired, the host defense status, the overall In the serum bactericidal test (SBT), samples of the serum of clinical severity of the infection, and the response of the host. the treated patient are obtained and incubated with the infecting Definitive therapy is initiated after the host response to the infec- organism in doubling dilutions with broth to determine the high- tion and to the empirical treatment has been monitored and the est dilution that is bactericidal. (Not all antimicrobial agents results from the microbiology laboratory—specifically, identifica- exhibit bactericidal activity; some exhibit only bacteriostatic activ- tion of the isolated organisms and the minimal inhibitory con- ity [see Table 1].) The drawing of serum specimens can be timed to centrations (MICs) of various antimicrobial agents—have been coincide with anticipated peak and trough antimicrobial levels. In assessed. effect, this test indirectly assesses both the susceptibility of the organism and the serum concentration of the antimicrobial agent, LABORATORY TESTS as well as the interactions between serum and organism and Many laboratory tests, if used in the proper context, can guide serum and drug.The NCCLS has developed proposed guidelines selection of optimal antimicrobial therapy. for the SBT.3 A comprehensive review of the technical and clini- In vitro susceptibility tests are indicated when the susceptibili- cal considerations associated with the SBT has been published.4 ty of an organism is not completely predictable or when certain other specific problems arise, such as the necessity of determin- ing whether resistance has developed during the course of thera- Factors Influencing Application of Antimicrobial Therapy py. An organism is generally considered susceptible if the con- ROUTE OF ADMINISTRATION centration of antimicrobial agent necessary to inhibit its growth is lower than that usually attainable in body fluids, particularly Many antibiotics are absorbed sufficiently well via the oral blood, cerebrospinal fluid, or urine. route to provide effective blood levels in patients with normal GI The disk diffusion method has been standardized by the function.5 The enteral absorption of some antimicrobials is
  2. 2. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 2 impeded by food and some medications (e.g., antacids). Many ume, glomerular filtration rule (GFR), and hepatic metabolic antibiotics cannot be given intramuscularly because of local pain activity often reduce the maternal serum levels of antimicrobials or necrosis at the injection site. Intravenous administration must by 10% to 50%, especially late in pregnancy and in the early be used in the treatment of major and life-threatening infections postpartum period. In some women, delayed gastric emptying such as suppurative diffuse peritonitis. In many cases, patients are may reduce the absorption of antibiotics that have been admin- clinically stable during intravenous treatment, and it is often pos- istered orally during pregnancy. sible to discharge them and to administer parenteral antibiotics Even though 25% to 40% of women receive antibiotics during on an outpatient basis. Supervision by special teams of physi- pregnancy, data regarding safety and efficacy in this setting are cians, nurses, and pharmacists is required6; antibiotics can be often scarce. Some general recommendations have been pro- administered either in the hospital outpatient department or at posed, but they are intended only as a guide [see Table 2]; in all home if competent family members are available. New antibi- cases, therapy must be individualized, and both the indications for otics with long half-lives can be used with improved intravenous antibiotics and the possible risks to mother and fetus must be con- catheters and delivery devices in simplified regimens; this leads sidered. Individual decisions are also required for lactating moth- to substantial economic benefits, enhanced patient comfort, and ers; although most antimicrobials appear safe for breast-fed in- good therapeutic results with few complications.7 fants, chloramphenicol and the tetracyclines should be avoided.9 HOST FACTORS Advanced Age Physiologic changes that occur with age can alter the phar- Hypersensitivity to Antibiotics macokinetics of antimicrobial agents. For example, decreased Because of widespread exposure to antimicrobial agents, many gastric acidity and intestinal motility can impair drug absorp- patients develop allergies to them.8 A careful history of hyper- tion; increased body fat and decreased serum albumin levels can sensitivity should thus be obtained [see Hypersensitivity Reac- alter drug distribution; and decreased hepatic blood flow and tions, below]. enzymatic action can delay drug metabolism. Although these factors have not consistently affected antibiotic levels in the Concurrent Illnesses elderly, the decrease in GFR that occurs with age can lead to the Patients with immunosuppressive illnesses are vulnerable to accumulation of drugs excreted by the kidney. The high thera- opportunistic pathogens. These patients may require broader peutic index of the penicillins and cephalosporins obviates antimicrobial coverage as well as intense therapy for ordinary major changes in dosage schedules in elderly patients who have pathogens. The same is true to a lesser extent for patients with a normal serum creatinine levels. However, in the case of amino- chronic debilitating illness. Patients with renal insufficiency or glycosides and vancomycin, decreased dosage schedules are liver disease may be unusually susceptible to direct drug toxicity. often required; ideally, drug levels should be measured and renal function should be monitored when these agents are given. The Pregnancy dosage of amantadine and rimantadine should also be reduced The administration of antimicrobial agents during pregnancy in elderly patients. and in the postpartum period poses several problems. Foremost is the question of safety, both for the mother and the fetus or neonate. Although most antibiotics cross the placenta and enter Antibiotic Selection for Infections in Surgical Patients maternal milk, the concentrations to which the fetus or neonate The term surgical infection is difficult to define, but for the is exposed vary widely. Because the immature liver may lack the purposes of this chapter, it means infections that are related to enzymes required to metabolize certain drugs, pharmacokinetics surgical procedures or that require, in addition to antibiotic ther- and toxicities in the fetus are often very different from those in apy, surgical debridement or control of the source of the infec- older children and adults.Teratogenicity is a major concern when tion. Such infections include infections of the soft tissues of the any drug is administered during pregnancy. Finally, it may be integument; muscles; bones; and body cavities (e.g., empyema, necessary to alter the dosage schedules of drugs that appear to be intra-abdominal infections, pyelonephritis, and infections of the safe to use during pregnancy; increases in maternal blood vol- retroperitoneum). A framework for antibiotic selection for intra-abdominal infections is presented [see Table 3]; this framework can be mod- Table 1 Bactericidal and Bacteriostatic Agents155 ified for the selection of antibiotic for other types of surgical infection. A therapeutic regimen for the treatment of intra- Bactericidal Agents Bacteriostatic Agents abdominal infection should include agents that are active against Staphylococcus aureus, enteric gram-negative bacilli, and anaer- Aminoglycosides* Chloramphenicol obes, including Bacteroides fragilis. The regimen that has been Aztreonam Clindamycin regarded as the gold standard consists of an aminoglycoside, to Bacitracin Erythromycin cover the enteric gram-negative organisms, and clindamycin or Cephalosporins Sulfonamides metronidazole, to cover the anaerobes; other approaches, how- Imipenem Tetracyclines ever, look promising. Penicillins Trimethoprim A well-designed, controlled, prospective, randomized trial that Polymyxins† Quinolones‡ compared imipenem therapy with acceptable aminoglycoside- Vancomycin based regimens supports the use of imipenem as monotherapy for intra-abdominal infections in which an enteric mixed flora is *Including streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, and netilmicin. anticipated.10 When the analysis was restricted to the residual † Including polymyxin B and colistimethate. effect of treatment assignment, a significant improvement in out- ‡ Including norfloxacin and ciprofloxacin. come was found in the patients receiving imipenem (P = 0.043).
  3. 3. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 3 Table 2 Antibiotics in Pregnancy155 Major Toxic Potential Pharmacology Drug Maternal Excreted in Maternal Fetal Serum Levels Mother’s Milk Considered safe Cephalosporins Allergies None known Decreased Trace Erythromycin base Allergies, GI intolerance None known Decreased Yes Penicillins Allergies None known Decreased Trace Spectinomycin ? None known ? ? Use with caution Aminoglycosides Ototoxicity, nephrotoxicity Ototoxicity Decreased Yes Clindamycin Allergies, colitis None known Unchanged Trace Ethambutol Optic neuritis Probably safe ? ? Isoniazid Allergies, hepatotoxicity Neuropathy, seizures Unchanged Yes Rifampin Hypersensitivity, hepatotoxicity Probably safe Unchanged Yes Sulfonamides Allergies, crystalluria Kernicterus (at term), hemolysis Unchanged Yes (contraindicated at term) (G6PD deficiency) Avoid if possible Metronidazole Hypersensitivity, alcohol intolerance, None known (teratogenic in animals) Probably unchanged Yes neuropathy Contraindicated Chloramphenicol Blood dyscrasias Gray syndrome Unchanged Yes Erythromycin estolate Hepatotoxicity None known Decreased Yes Nalidixic acid GI intolerance Increased intracranial pressure ? ? Nitrofurantoin Allergies, neuropathy, GI intolerance Hemolysis (G6PD deficiency) Decreased Trace Norfloxacin, ciprofloxacin, GI intolerance Arthropathies in immature animals ? ? ofloxacin, lomefloxacin Tetracyclines Hepatotoxicity, renal failure Tooth discoloration and dysplasia, Probably unchanged Yes impaired bone growth Trimethoprim Hypersensitivity Teratogenicity Unchanged Yes Meropenem was found to be as effective as imipenem for the addressed by guidelines published by members of the Surgical treatment of moderately severe intra-abdominal infections.11 Infection Society.15 The third-generation cephalosporins have Ertapenem has a pharmacokinetic profile and an antimicrobial been proposed as candidates for single-agent therapy for infection spectrum that support its use as a once-daily agent for the treat- in the abdominal cavity because their spectra of activity encom- ment of common mixed aerobic and anaerobic infections. A pass both the aerobic gram-negative bacilli and some of the prospective, randomized, controlled, double-blind trial com- anaerobic isolates that cause infection in this region. No pared ertapenem with piperacillin-tazobactam as therapy follow- cephalosporin, of any generation, has been shown to have a clear ing adequate surgical management of complicated intra-abdom- advantage over an aminoglycoside-clindamycin combination in inal infections.The modified intent-to-treat population consisted the treatment of intra-abdominal infections. of 633 patients, of whom 396 met all criteria for the evaluable Interpretation of overall results in intra-abdominal infections is population. Patients with a wide range of infections were en- difficult because of the numerous variables involved, including rolled. A prospective expert-panel review was conducted to the diversity of the possible infectious processes, the variable assess the adequacy of surgical source control in patients in quality of the surgical technique employed, the variety of the whom therapeutic failure was a component of evaluability. For patient characteristics observed, the possibility of one or more the modified intent-to-treat groups, 245 of 311 patients treated underlying diseases, and the differing doses of antibiotics used in with ertapenem (78.8%) were cured; 232 of 304 patients individual studies.16 Most third-generation cephalosporins do not (76.3%) treated with piperacillin-tazobactam were cured. Of 203 cover anaerobes well and should be used in conjunction with an microbiologically evaluable patients treated with ertapenem, 176 antianaerobic agent, such as clindamycin or metronidazole, for (86.7%) were cured; 157 of the 193 patients (81.3%) treated empirical therapy for serious intra-abdominal infections. In a with piperacillin-tazobactam were cured. In this study, ertapen- recent prospective, randomized, double-blind study, cefoxitin was em, 1 g once a day, was equivalent to piperacillin-tazobactam, found to be comparable to imipenem with regard to outcome 3.375 g every 6 hours, in the treatment of a range of intra- (defined as survival); failure to cure infections was attributed to abdominal infections. Ertapenem may be a useful option that resistant organisms at the primary site in the cefoxitin arm of the could eliminate the need for combination therapy, multidose trial.17 antibiotic regimens, or both for the empirical treatment of intra- abdominal infections.12 Appropriate surgical control of the source of the intra-abdom- Adverse Reactions to Antimicrobial Agents inal infection is of utmost importance in determining outcome; There are three general types of adverse reactions to antimi- antibiotics play a necessary but secondary role.13,14 The contro- crobial agents: hypersensitivity reactions (which are not dose versies regarding the pathogenicity of enterococci have been related), direct drug toxicity (which usually is dose related and
  4. 4. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 4 Third Pass 06/24/03 Table 3 Antibiotic Selection for Infections in Surgical Patients Type of Infection Expected Pathogen First Choice I.V. Rx Second Choice I.V. Rx Switch to P.O. Choice Brain infection (abscess, subdural empyema, intracranial suppurative thrombophlebitis) Staphylococcus aureus, Traumatic brain injury Enterobacteriaceae, Cefepime, 2 g I.V. q. 8 hr Meropenem, 1 g I.V. q. 8 hr Not recommended Pseudomonas aeruginosa Nafcillin, 2 g I.V. q. 4 hr or Postneurosurgical S. aureus, S. epidermidis Cefepime, 2 g I.V. q. 8 hr Meropenem, 1 g I.V. q. 8 hr Linezolid, 600 mg p.o., q. 12 hr procedure or If methicillin resistant: Linezolide, 600 mg I.V. q. 12 hr Vascular graft infection Vancomycin, 1 g I.V. S. aureus, Enterobacteriaceae, plus Meropenem, 1 g I.V. q. 8 hr Moxifloxacin, 400 mg p.o. and Arteriovenous graft/shunt and remove graft remove graft enterococci Gentamicin, 240 mg I.V. and remove graft Cefepime, 2 g I.V. q. 12 hr Aortic graft or Ceftizoxime, 2 g I.V. q. 8 hr Levofloxacin, 500 mg p.o., q. 24 hr S. aureus, S. epidermidis, (treat with antibiotics Enterobacteriaceae Imipenem, 1 g I.V. q. 8 hr or or until graft is replaced) or Cefotaxime, 2 g I.V. q. 6 hr Moxifloxacin, 400 mg p.o., q. 24 hr Meropenem, 1 g I.V. q. 8 hr Intra-abdominal infection (peritonitis, abscess) Ceftizoxime, 2 g I.V. q. 8 hr Levofloxacin, 500 mg p.o., q. 24 hr Gastric perforation Candida, oral anaerobes, Cefazolin, 1 g I.V. q. 8 hr or or (peptic ulcer disease) S. aureus Cefotaxime, 2 g I.V. q. 6 hr Moxifloxacin, 400 mg p.o., q. 24 hr Cefepime, 2 g I.V. q. 12 hr or Ceftizoxime, 2 g I.V. q. 8 hr Levofloxacin, 500 mg p.o., q. 24 hr Gastric perforation S. aureus, S. epidermidis, Imipenem, 1 g I.V. q. 8 hr or or (malignancy) Enterobacteriaceae, Candida or Cefotaxime, 2 g I.V. q. 6 hr Moxifloxacin, 400 mg p.o., q. 24 hr Meropenem, 1 g I.V. q. 8 hr Levofloxacin, 500 mg p.o., q. 24 hr Cholecystitis with Escherichia coli, Klebsiella, Piperacillin-tazobactam, 4.5 g I.V. Cefotaxime, 2 g I.V. q. 6 hr or gangrene/perforation enterococci q. 8 hr Moxifloxacin, 400 mg p.o., q. 24 hr Emphysematous Piperacillin-tazobactam, 4.5 g I.V. Clostridium perfringens q. 8 hr Ertapenem, 1 g I.V. q. 24 hr Clindamycin, 300 mg p.o., q. 8 hr cholecystitis Imipenem, 1 g I.V. q. 8 hr Levofloxacin, 500 mg p.o., q. 24 hr Ascending cholangitis E. coli, Klebsiella, enterococci or Cefoperazone, 2 g I.V. q. 12 hr or Meropenem, 1 g I.V. q. 8 hr Moxifloxacin, 400 mg p.o., q. 24 hr Clindamycin, 300 mg p.o., q. 8 hr Imipenem, 1 g I.V. q. 8 hr Piperacillin-tazobactam, plus or 4.5 g I.V. q. 8 hr Infected hemorrhagic/ Enterobacteriaceae, Levofloxacin, 500 mg p.o., q. 24 hr necrotizing pancreatitis Bacteroides fragilis Meropenem, 1 g I.V. q. 8 hr or or or Ampicillin-sulbactam, 3 g I.V. q. 6 hr Moxifloxacin, 400 mg p.o., q. 24 hr Ertapenem, 1 g I.V. q. 24 hr Metronidazole, 1 g I.V. q. 24 hr Imipenem, 1 g I.V. q. 8 hr Metronidazole, 500 mg p.o., q. 12 hr plus or plus Liver abscess (bacterial) Enterobacteriaceae, Levofloxacin, 500 mg I.V. B. fragilis Meropenem, 1 g I.V. q. 8 hr Levofloxacin, 500 mg p.o., q. 24 hr q. 24 hr or or or Ertapenem, 1 g I.V. q. 24 hr Moxifloxacin, 400 mg p.o., q. 24 hr Moxifloxacin, 400 mg I.V. q. 24 hr Liver abscess Tinidazole, 2 g/day p.o. in Entamoeba histolytica Metronidazole, 750 mg p.o., q. 8 hr Not applicable (amebiasis) three divided doses (continued )
  5. 5. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 5 Table 3 (continued ) Type of Infection Expected Pathogen First Choice I.V. Rx Second Choice I.V. Rx Switch to P.O. Choice Intra-abdominal Infection (peritonitis, abscess) (continued) Distal small bowel, appendix, colon, rectum Piperacillin-tazobactam, 4.5 g I.V. Cefoxitin, 2 g I.V. q. 6 hr Ciprofloxacin, 250–750 mg p.o., q. perforation in nonhospi- Enterobacteriaceae, enterococ- q. 8 hr or 12 hr talized patient (mild to ci, B. fragilis or plus Ampicillin-sulbactam, 3 g I.V. moderate infection) Ertapenem, 1 g I.V. q. 24 hr q. 6 hr Metronidazole, 500 mg p.o., q. 12 hr Distal small bowel, Tobramycin, 5 mg/ kg load- appendix, colon, rec- ing dose, then 3 mg/kg Imipenem, 1 g I.V. q. 8 hr I.V. q. 8 hr tum perforation in hos- Enterobacteriaceae, entero- cocci, B. fragilis, P. aerugi- or plus Moxifloxacin, 400 mg p.o., q. 24 hr pitalized patient (severe infection requiring ICU nosa, Acinetobacter Meropenem, 1 g I.V. q. 8 hr Clindamycin, 900 mg I.V. support) q. 8 hr Ciprofloxacin, 250–750 mg p.o., q. Spontaneous bacterial 12 hr Enterobacteriaceae Ciprofloxacin, 400 mg I.V. q. 12 hr Cefepime, 2 g I.V. q. 12 hr peritonitis plus Metronidazole, 500 mg p.o., q. 12 hr Pelvic inflammatory disease (tubo-ovarian abscess, salpingitis, endometritis, infected abortion) Ciprofloxacin, 250–750 mg p.o., q. Enterobacteriaceae, B. fragilis, 12 hr Mild to moderate infec- Neisseria gonorrhoeae, Moxifloxacin, 400 mg p.o., q. 24 hr None tion (outpatients) plus Chlamydia trachomatis Doxycycline, 100 mg p.o., q. 12 hr Levofloxacin, 500 mg p.o., q. Enterobacteriaceae, B. fragilis, Doxycycline, 200 mg I.V. q. 12 hr 24 hr Severe infection (hospi- N. gonorrhoeae, C. tracho- plus plus Moxifloxacin, 400 mg p.o., q. 24 hr talized patient) matis Clindamycin, 600 mg I.V. q. 8 hr Metronidazole, 1 g I.V. q. 24 hr manifests in a single organ or, occasionally, in several organs), and probably secondary to injury to the red cell membrane. Flucyto- microbial superinfection. sine causes bone marrow suppression (leukopenia or pancytope- nia) when its excretion is reduced by renal failure. Linezolid can HYPERSENSITIVITY REACTIONS also produce myelosuppression; although experience is limited, A history of allergies should be taken before antimicrobial ther- bone marrow function usually recovers when the drug is discon- apy is initiated in any patient. More information is available tinued. Neutropenia can occur during therapy with penicillins, regarding allergies to the penicillins than allergies to other agents, cephalosporins, or vancomycin. It may be severe, but it is self-lim- but skin eruptions, drug fever, and even anaphylaxis may be pro- ited; recovery occurs 1 to 7 days after the antibiotic is withdrawn. duced by many antibiotics. Allergic reactions occur in 1% to 10% Penicillins inhibit platelet aggregation by adenosine diphosphate, of patients who receive penicillin. Fatal anaphylactic reactions are which may account for the bleeding that occurs in some patients much less frequent. receiving these antibiotics in high doses. Various cephalosporins may produce coagulopathies by prolonging the prothrombin DIRECT DRUG TOXICITY time; the methylthiotetrazole side chain present in cephalosporins Although antimicrobials can produce damage to virtually all such as cefotetan appears to be responsible. human organ systems, the potential for toxicity varies widely from Antibiotics may produce a wide range of toxic effects on the drug to drug.18 The principal antibiotics that are directly toxic to central and peripheral nervous systems. Ototoxicity, either the kidney are aminoglycosides, polymyxins, and amphotericin B; vestibular or auditory, can be produced by any of the aminogly- azotemia and renal tubular damage may be caused by any of cosides; neuromuscular blockade is much less common. these drugs. Patients with preexisting renal insufficiency are at Minocycline has occasionally been reported to produce signifi- increased risk for toxic reactions to various antibiotics, including cant vestibular reactions. Vancomycin can cause auditory neuro- nephrotoxicity, coagulopathies and other hematologic toxicities, toxicity. Intravenous administration of large doses of penicillin seizures, and ototoxicity and other neurotoxicities. and other β-lactams may produce seizures, especially when Penicillins, cephalosporins, tetracyclines, and rifampin can administered in very high doses or when given to azotemic cause hemolytic anemia, thrombocytopenia, and leukopenia that patients or to patients with underlying epilepsy. involve an immune mechanism, but these reactions are uncom- Metronidazole can sometimes cause ataxia, encephalopathy, mon. Macrolides and trimethoprim-sulfamethoxazole have been seizures, or peripheral neuropathies. Ofloxacin has been reported associated with agranulocytosis. Trimethoprim can produce ane- to cause seizures; mania has been attributed to clarithromycin. mia, leukopenia, and thrombocytopenia from folate deficiency; Optic neuritis, usually manifested by decreased visual acuity and the effect is reversible with folinic acid. Amphotericin B com- decreased perception of the color green, may occur as a side effect monly produces a reversible normocytic normochromic anemia, of ethambutol.
  6. 6. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 6 Table 4 Antimicrobial Drugs of Choice for Various Infections in Adults18 Causative Organism Drug of Choice Alternative Drugs Staphylococcus aureus Methicillin-sensitive Linezolid; quinupristin-dalfopristin Methicillin-resistant1 Vancomycin,2 with or without rifampin or Trimethoprim-sulfamethoxazole (TMP-SMX),2 with or without gentamicin rifampin2; a fluoroquinolone3; a tetracycline4 Penicillinase-resistant penicillin5 A cephalosporin,6 clindamycin, vancomycin,7 meropenem or imipenem,8 ticarcillin–clavulanic acid, ampicillin-sulbactam, amoxicillin–clavulanic acid, piperacillin-tazobactam, a fluoroquinolone3 Coagulase-negative Vancomycin,7 with or without rifampin2 or Linezolid, quinupristin-dalfopristin, a cephalosporin, a penicilli- staphylococci9 gentamicin nase-resistant penicillin, meropenem or imipenem,8 a fluoro- quinolone3 Anaerobic streptococcus Penicillin G 10 Clindamycin, a cephalosporin,6 vancomycin7 Gram-Positive Cocci (Peptostreptococcus) Streptococcus bovis Penicillin G 10,11 A cephalosporin,6 vancomycin7 Groups A, G, and C streptococci Penicillin G10,12 or penicillin V A cephalosporin,6 vancomycin,7 an erythromycin,13 clindamycin, clarithromycin, azithromycin Group B streptococcus Penicillin G10,12 or ampicillin A cephalosporin,6 vancomycin,7 an erythromycin S. pneumoniae (pneumococcus) Penicillin sensitive Penicillin G10,12 or penicillin V, amoxicillin An erythromycin,12,13 a cephalosporin,6 meropenem or imipenem,8 vancomycin,7,12 azithromycin, clarithromycin, a fluoroquinolone; a tetracycline4 Non–penicillin sensitive Vancomycin; ceftriaxone or cefotaxime6; — levofloxacin, moxifloxacin, or gatifloxacin3; linezolid; quinupristin-dal- fopristin; imipenem or meropenem Viridans streptococcus Penicillin G,10,11 with or without A cephalosporin,6 vancomycin7 gentamicin Enterococcus Endocarditis or other serious Penicillin or ampicillin, plus gentamicin14 or Vancomycin,7 with gentamicin or streptomycin; linezolid; infection streptomycin quinupristin-dalfopristin Uncomplicated urinary tract Ampicillin or amoxicillin A fluoroquinolone,3 nitrofurantoin,15 fosfomycin infection Bacillus cereus, B. subtilis Vancomycin Meropenem or imipenem,8 clindamycin Gram-Positive Bacilli Bacillus anthracis Penicillin G Ciprofloxacin,3 a tetracycline,4 an erythromycin2 Clostridium difficile Metronidazole16 Vancomycin16 C. perfringens Penicillin G; clindamycin Metronidazole, meropenem or imipenem,8 chloramphenicol7 C. tetani Metronidazole Penicillin G, a tetracycline4 Corynebacterium diphtheriae An erythromycin Penicillin G Corynebacterium, JK group Vancomycin Penicillin G, with gentamicin; an erythromycin Listeria monocytogenes Ampicillin, with or without gentamicin TMP-SMX Propionibacterium Penicillin G Clindamycin, an erythromycin Moraxella (formerly Branhamella) Cefuroxime,6 a fluoroquinolone3 TMP-SMX, amoxicillin–clavulanic acid, an erythromycin, a tetra- Gram-Negative Cocci catarrhalis cycline, third-generation cephalosporins, clarithromycin, azithromycin Neisseria gonorrhoeae17 Ceftriaxone or cefixime,6 ciprofloxacin, Cefotaxime,10 penicillin or ampicillin ofloxacin, or gatifloxacin3 N. meningitidis Meningitis, bacteremia Penicillin G A third-generation cephalosporin,6 TMP-SMX, a fluoroquinolone,3 chloramphenicol7 Carrier state Rifampin Minocycline, ciprofloxacin Bacteroides GI tract strains (B. fragilis) Metronidazole or clindamycin Cefoxitin, cefotetan, ceftizoxime, or cefmetazole; chloramphen- Enteric Gram-Negative Bacilli icol18; imipenem or meropenem8; ticarcillin–clavulanic acid; ampi- cillin-sulbactam, piperacillin-tazobactam Respiratory tract strains Penicillin G or clindamycin Metronidazole, cefoxitin,6 cefotetan, ceftizoxime, cefmetazole, chloramphenicol7 Campylobacter fetus Imipenem or meropenem8 Gentamicin C. jejuni Azithromycin or an erythromycin A fluoroquinolone,3 a tetracycline,4 gentamicin7 Citrobacter Imipenem or meropenem8 A fluoroquinolone,3 amikacin; TMP-SMX; a tetracycline4; a third- generation cephalosporin6 Enterobacter Imipenem or meropenem8 A third-generation cephalosporin6; for serious infections, use with a fluoroquinolone3 or gentamicin; gentamicin, tobramycin, amikacin, a fluoroquinolone,3 a carboxypenicillin or acylaminopenicillin,19 aztreonam20 Escherichia coli Ampicillin, a cephalosporin,6 a fluoro- Gentamicin,21 tobramycin, amikacin, imipenem or meropenem,8 quinolone,3 TMP-SMX22 aztreonam20 Note: all superscript numbers refer to footnotes that follow table.
  7. 7. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 7 Table 4 (continued) Causative Organism Drug of Choice Alternative Drugs Helicobacter pylori Tetracycline with metronidazole and bis- Amoxicillin with metronidazole and bismuth subsalicylate; tetracy- muth subsalicylate or omeprazole with cline with clarithromycin and bismuth subsalicylate; clarithromycin amoxicillin and clarithromycin with omeprazole; amoxicillin with clarithromycin Klebsiella A cephalosporin6 Imipenem or meropenem,9 gentamicin,23 tobramycin, amikacin, TMP-SMX,21 a carboxypenicillin or acylaminopenicillin,21 amoxi- Enteric Gram-Negative Bacilli (continued) cillin–clavulanic acid, ampicillin-sulbactam, ticarcillin–clavulanic acid, piperacillin-tazobactam, aztreonam,20 a fluoroquinolone3 Proteus mirabilis Ampicillin A cephalosporin, gentamicin or tobramycin, chloramphenicol,7 a car- boxypenicillin or acylaminopenicillin,19 imipenem or meropenem,8 TMP-SMX, aztreonam,20 a fluoroquinolone3 non-mirabilis, including P. vul- A third-generation cephalosporin6 Gentamicin, tobramycin, amikacin, a carboxypenicillin or acyl- garis, Morganella morganii, aminopenicillin,19 imipenem or meropenem,8 aztreonem,20 ampi- and Providencia rettgeri cillin-sulbactam, ticarcillin–clavulanic acid, piperacillin-tazobactam, amoxicillin–clavulanic acid, a fluoroquinolone3 Providencia stuartii A third-generation cephalosporin6 An aminoglycoside, TMP-SMX,21 imipenem or meropenem,8 aztreonam,20 a carboxypenicillin or acylaminopenicillin,19 a fluoroquinolone3 Salmonella typhi Ceftriaxone or a fluoroquinolone3 Chloramphenicol or ampicillin,22 TMP-SMX Other Salmonella species Ceftriaxone or cefotaxime or a Ampicillin or amoxicillin, TMP-SMX, chloramphenicol7 fluoroquinolone3 Serratia Imipenem or meropenem A third-generation cephalosporin,6 gentamicin or amikacin, a car- boxypenicillin or acylaminopenicillin,19 chloramphenicol,7 aztreo- nam, a fluoroquinolone3 Shigella A fluoroquinolone3 TMP-SMX, ampicillin, ceftriaxone, azithromycin Acinetobacter (Herellea) Imipenem or meropenem8 Tobramycin, gentamicin, amikacin, doxycycline, minocycline, a car- boxypenicillin or acylaminopenicillin,19 TMP-SMX, a fluoro- quinolone,3 ceftazidime Aeromonas hydrophilia TMP-SMX 2 A fluoroquinolone,3 gentamicin, tobramycin, imipenem or meropenem8 Bartonella henselae Azithromycin Ciprofloxacin,3 TMP-SMX, gentamicin; rifampin, erythromycin (cat-scratch disease) Bartonella henselae Erythromycin Doxycycline, azithromycin (bacillary angiomatosis) Bordetella pertussis Erythromycin TMP-SMX; azithromycin or clarithromycin (whooping cough) Brucella A tetracycline, with rifampin A tetracycline with gentamicin or streptomycin; chloramphenicol,7 with or without streptomycin; TMP-SMX 2 with or without gentami- cin; ciprofloxacin3 with rifampin Eikenella corrodens Ampicillin An erythromycin, a tetracycline,4 amoxicillin–clavulanic acid, ampi- cillin-sulbactam, ceftriaxone Francisella tularensis (tularemia) Streptomycin Gentamicin, a tetracycline,4 chloramphenicol,7 ciprofloxacin3 Other Gram-Negative Bacilli Fusobacterium Penicillin Clindamycin, metronidazole, chloramphenicol7; cefoxitin Gardnerella (formerly Haemo- Metronidazole2 (oral) Intravaginal metronidazole, intravaginal or oral clindamycin philus) vaginalis Haemophilus influenzae TMP-SMX Ampicillin or amoxicillin; a tetracycline4; amoxicillin–clavulanic acid, Bronchitis, otitis media cefuroxime axetil, ceftizoxime, clarithromycin, azithromycin, a fluoroquinolone3 Meningitis, epiglottitis, life- Cefotaxime or ceftriaxone Chloramphenicol,24 meropenem9 threatening infections Legionella species Azithromycin or a fluoroquinolone3 Erythromycin, rifampin,25 TMP-SMX,2 doxycycline4 Pasteurella multocida Penicillin G A tetracycline,4 a cephalosporin,6 amoxicillin–clavulanic acid, ampi- cillin-sulbactam Calymmatobacterium granuloma- TMP-SMX A tetracycline4; ciprofloxacin with or without rifampin tis (granuloma inguinale) H. ducreyi (chancroid) Ceftriaxone or azithromycin A fluoroquinolone3 Pseudomonas aeruginosa Urinary tract infections Ciprofloxacin3 Levofloxacin; gentamicin or tobramycin; amikacin; ceftazidime,6 with or without gentamicin or tobramycin; imipenem or meropenem8; aztre- onam,20 a carboxypenicillin or acylaminopenicillin19 Other infections Gentamicin or tobramycin, with or without Amikacin, with or without a carboxypenicillin or acylaminopenicillin19; a carboxypenicillin or acylamino- ciprofloxacin7 penicillin19; ceftazidime or cefipime; imi- penem or meropenem8; aztreonam,20 alone or with gentamicin or tobramycin P. cepacia TMP-SMX Chloramphenicol,7 ceftazidime,2 imipenem2,8 or meropenem8 Streptobacillus moniliformis Penicillin G A tetracycline,4 streptomycin (rat-bite fever) Note: all superscript numbers refer to footnotes that follow table.
  8. 8. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 8 Table 4 (continued) Causative Organism Drug of Choice Alternative Drugs Vibrio cholerae A tetracycline4 TMP-SMX, a fluoroquinolone3 Other Gram-Negative V. vulnificus A tetracycline4 Cefotaxime Bacilli (continued) Agents of Vincent stomatitis Penicillin G A tetracycline,4 an erythromycin (trench mouth) Stenotrophomonas (formerly TMP-SMX Minocycline, ceftazidime,6 a fluoroquinolone3 Xanthomonas) maltophilia Yersinia enterocolitica TMP-SMX 2 A fluoroquinolone, gentamicin,2 tobramycin,2 amikacin, cefotaxime2,6 or ceftizoxime2,6 Y. pestis (plague) Streptomycin with or without a A tetracycline,4 chloramphenicol,7 gentamicin,2 TMP-SMX tetracycline Mycobacterium avium complex Clarithromycin or azithromycin plus Rifampin, amikacin one or more of the following: ethambutol, rifabutin, ciprofloxacin M. fortuitum Amikacin2 with clarithromycin Rifampin,2 cefoxitin, a sulfonamide, doxycycline, ethambutol, Acid-Fast Bacilli linezolid M. kansasii Isoniazid with rifampin, with or without Cycloserine, ethionamide, clarithromycin ethambutol or streptomycin M. leprae Dapsone 7 with rifampin, with or without Minocycline,4 ofloxacin or sparfloxacin,3 clarithromycin clofazimine M. marinum (balnei)26 Minocycline TMP-SMX, rifampin, clarithromycin, doxycycline M. tuberculosis27 Isoniazid with rifampin, and pyrazinamide Ciprofloxacin or ofloxacin; third-line agent with or without ethambutol or strepto- mycin mycetes Actino- Actinomyces israelii Penicillin G A tetracycline4; an erythromycin; clindamycin Nocardia TMP-SMX Minocycline, sulfisoxazole, imipenem or meropenem,8 amikacin,2 cycloserine, linezolid Chlamydia psittaci (psittacosis) A tetracycline4 Chloramphenicol7 C. trachomatis Inclusion conjunctivitis An erythromycin (oral or I.V.) A sulfonamide (topical plus oral) Lymphogranuloma venereum A tetracycline4 An erythromycin Chlamydia Pneumonia An erythromycin A sulfonamide Trachoma Azithromycin A tetracycline4 (topical plus oral), a sulfonamide (topical plus oral) Urethritis or pelvic inflammatory Doxycycline or azithromycin Erythromycin, ofloxacin, amoxicillin disease C. pneumoniae An erythromycin or clarithromycin or A tetracycline azithromycin; a fluoroquinolone Mycoplasma pneumoniae An erythromycin, clarithromycin or — plasma Myco- azithromycin; a fluoroquinolone,3 doxycycline4 Ureaplasma urealyticum An erythromycin A tetracycline,4 clarithromycin, or azithromycin; ofloxacin3 Various rickettsial organisms Doxycycline4 Chloramphenicol,7 a fluoroquinolone,3 rifampin Rickettsia Rocky Mountain spotted fever, epidemic and endemic (murine) typhus, rickettsial pox, Q fever, scrub typhus Borrelia burgdorferi (Lyme Doxycycline or amoxicillin or Penicillin, an erythromycin, clarithromycin, azithromycin, Spirochetes disease) ceftriaxone cefuroxime B. recurrentis (relapsing fever) A tetracycline4 Penicillin G Leptospira Penicillin G A tetracycline,4 an erythromycin Treponema pallidum Penicillin G A tetracycline,4 an erythromycin, ceftriaxone 1. Some strains of S. aureus and most strains of coagulase-negative staphylococci pected penicillin allergy but not in patients with serious hypersensitivity (especially imme- are resistant to penicillinase-resistant penicillins; these strains are also resistant to ceph- diate anaphylactic or accelerated urticarial reactions). Patients allergic to penicillin may alosporins. be hypersensitive to cephalosporins. Only third-generation cephalosporins are effective 2. Not approved for this indication by the FDA. in bacterial meningitis. 3. None of these drugs is recommended for children. In 1999, the FDA limited tro- 7. In view of the occurrence of adverse reactions, this drug should be used only for seri- vafloxacin to inpatient use for limb- or life-threatening infections. ous infections and when less toxic drugs are ineffective. 4. Doxycycline is the safest tetracycline for treatment of extrarenal infections in renal in- 8. Imipenem and meropenem are β-lactam antibiotics that should be used with caution sufficiency. Tetracyclines should be avoided in pregnant women and in children younger in patients who are allergic to penicillins and cephalosporins. than 8 yr. 9. In vitro sensitivity testing with cephalosporins or penicillins may be misleading be- 5. For severe infections, I.V. nafcillin or oxacillin should be used. For mild infections, oral cause of heteroresistance and because these antibiotics may be bacteriostatic only. For cloxacillin, dicloxacillin, or oxacillin may be employed. Between 1% and 2% of S. aureus serious infections, vancomycin is preferred (see text). strains are resistant to penicillinase-resistant penicillins (and usually to cephalosporins) 10. Crystalline penicillin G is administered parenterally for serious infections. For less se- but are susceptible to vancomycin. High doses of penicillin G, ampicillin, amoxicillin, car- vere infections caused by pneumococci, group A streptococci, gonococci, or T. palli- benicillin, or ticarcillin do not overcome the clinical resistance of penicillinase-producing dum, procaine penicillin is administered I.M. once or twice daily. For mild infections staphylococci to these drugs. caused by streptococci and pneumococci, oral penicillin V is preferable to oral penicillin G. 6. Cephalosporins are sometimes used as alternatives to penicillin in patients with sus- Benzathine penicillin G is given I.M. (once monthly for the prophylaxis of rheumatic fever,
  9. 9. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 9 Table 4 (continued) a single injection for the treatment of group A streptococcal pharyngitis) when patients’ 18. In CNS infection, metronidazole or chloramphenicol should be used. compliance for oral medication is questionable and for treatment of syphilis, in one to 19. The carboxypenicillins are carbenicillin and ticarcillin; the acylaminopenicillins are three doses at weekly intervals, depending on the stage of the disease. mezlocillin, azlocillin, and piperacillin. When one of these drugs is used for a severe infec- 11. The combination of penicillin G with streptomycin for the first 2 wk of treatment of tion, an aminoglycoside is often recommended as well. endocarditis caused by viridans streptococci is preferred by some. 20. Aztreonam is a β-lactam antibiotic; cross-sensitivity has not occurred, but use with 12. In patients with major allergy to penicillin, erythromycin is the alternative for respira- caution in patients allergic to penicillins, cephalosporins, or imipenem. tory tract infections; chloramphenicol is the preferred alternative for meningitis. Occa- 21. Principally in treatment of uncomplicated urinary tract infections. sional strains of pneumococci have high-level resistance to penicillin and to most other 22. Ampicillin or amoxicillin may be effective in milder cases. antibiotics except vancomycin. 23. In severely ill patients, an aminoglycoside is combined with a cephalosporin. 13. Some strains of pneumococci and group A streptococci are erythromycin resistant. 24. Some encapsulated H. influenzae (type b) strains and some unencapsulated strains 14. Various aminoglycosides have been used in synergistic combination with penicillin are resistant to ampicillin, and rare strains are resistant to chloramphenicol. Chloram- or vancomycin. Because of the appearance of enterococcal strains resistant to the syn- phenicol plus ampicillin (or chloramphenicol alone) should be used for initial treatment of ergistic action with streptomycin (but not gentamicin), gentamicin is preferred for use in meningitis or epiglottitis in children until the organism is identified and its susceptibility is the combination. determined. For adults with meningitis of unknown etiology and an indeterminate Gram 15. Contraindicated in pregnancy or in the presence of renal insufficiency. stain and in whom H. influenzae is suspected, chloramphenicol is added to ampicillin (or 16. Antibiotics may be administered orally for antibiotic-associated pseudomembra- penicillin G) for the first 24 hr until the results of culture are available. Ampicillin is pre- nous enterocolitis. Vancomycin and metronidazole are equally effective but metronida- ferred when the infecting strain of H. influenzae is susceptible. zole is much less expensive. 25. Not an FDA-approved use. Evidence for possible efficacy comes only from in vitro susceptibility testing and from treatment of infections in experimental animals. In both 17. Large doses of penicillin G or ampicillin (or amoxicillin) may be required because cases, L. pneumophila is highly susceptible to rifampin. some strains are resistant to these drugs. Penicillinase-producing gonococci, which are more resistant to penicillin, have appeared in the United States; spectinomycin is the 26. Most infections are self-limited without therapy. treatment of choice for infections with such strains. 27. Various combination treatments are available. Public Health Considerations Trovafloxacin was restricted for use in seriously ill patients because of hepatotoxicity, but other fluoroquinolones have not ANTIMICROBIAL RESISTANCE been implicated. The tetracyclines can occasionally cause fatty liver; hepatotoxicity is most likely to occur in patients receiving The extensive use of antimicrobial agents, especially in ICUs24 2 g or more daily by the intravenous route. Patients receiving and other health care facilities, strongly favors the selection of high-dose β-lactam antibiotics may develop hepatitis or cholesta- resistant microbial species, particularly bacterial strains harboring sis, presumably as a result of hypersensitivity reactions. Nitrofu- plasmids that confer transmissible resistance.25,26 Although rantoin may cause chronic active hepatitis in some patients. antibiotics have played a major role in the treatment of such infec- Erythromycins and sulfonamides have been associated with acute tions, the pathogens have responded to the antibiotic challenge, hepatitis, and a case of fatal hepatic necrosis has been attributed developing resistance to all available antimicrobial agents to a to fluconazole. greater or lesser degree. Specific mechanisms of resistance are GI reactions to antibiotics result either from direct irritation by evident in the reduced permeability of cell wall membranes, the drug, the occurrence of which is usually dose related, or from changes in the target sites of antimicrobial agents, enzymatic inac- bacterial overgrowth.19 Irritative GI side effects are usually pro- tivation of antibiotics, and the development of pathways bypass- duced when antibiotics are administered orally rather than par- ing antimicrobial targets.27 enterally. The predominant site of irritation varies from drug to The widespread use of antibiotics for animals compounds the drug; for example, erythromycin more commonly produces gas- problem; about 50% of the 25,000 tons of antibiotics that are sold tric irritation with epigastric distress and nausea, whereas tetra- annually in the United States are used in agriculture and aquicul- cyclines may produce diarrhea as well as upper GI symptoms. ture.28 Infections from highly resistant strains of Enterococcus, Some qualitative and quantitative changes in the intestinal flora Pneumococcus, Staphylococcus aureus, Gonococcus, Salmonella, occur after antibiotic administration; they may contribute to flat- Serratia, Klebsiella, Acinetobacter, Enterobacter, and Mycobacterium ulence and other lower GI symptoms, which are quite common have become important problems. Infections from resistant strains when broad-spectrum antibiotics are administered orally. can spread rapidly, first within an institution, then throughout a Selective overgrowth of Clostridium difficile can result in antibiot- community, and eventually even globally.29 Although antibiotic ic-induced pseudomembranous enterocolitis.20 resistance is a worldwide problem, control depends on local mea- Antibiotics may cause various other toxicities. Erythromycin and sures, beginning with the judicious prescription of antibiotics by other macrolides can cause prolongation of the QT interval and individual practitioners30 and with formulary restrictions that rein- polymorphic ventricular tachycardia; in rare instances, this toxicity force prudence.31 Patients harboring resistant strains should be occurs in the absence of predisposing factors, but it is more likely to identified rapidly, treated appropriately, and isolated as needed to occur in patients with significant heart disease and in patients tak- prevent the spread of infection. ing terfenadine, astemizole, or cisapride. Several fluoroquinolones, The incidence of suprainfection with cephalosporin therapy is such as moxifloxacin, gatifloxacin, and sparfloxacin, can have simi- actually quite low (< 5%); however, the organisms encountered lar effects on cardiac conduction.21,22 All fluoroquinolones can are often more virulent and difficult to eradicate than the original cause tendinitis. Trimethoprim-sulfamethoxazole can cause hyper- infecting pathogen.32 Commonly seen suprainfecting pathogens kalemia, particularly in azotemic patients. Sulfonamides, fluoro- include Enterobacter species, Pseudomonas aeruginosa, S. aureus, quinolones, and tetracyclines can produce photosensitivity.23 Acinetobacter species, enterococci, and Candida species. Because these organisms are generally multiresistant, therapy with antibi- MICROBIAL SUPERINFECTION otic combinations, including aminoglycosides, is usually neces- Antimicrobial therapy reduces susceptible organisms from the sary. There appear to be no significant differences among the normal flora of the skin, oral and genitourinary mucosae, and GI cephalosporins with respect to the incidence of suprainfection or tract and exerts selective pressures that favor survival of drug- the types of suprainfecting pathogens found. resistant organisms. Such resistant organisms can occasionally The most worrisome resistance is that of vancomycin-resistant establish a superinfection, either at the site of the original infec- enterococci (VRE). Risk factors for bloodstream infection with tion or at remote sites. VRE are an increasing APACHE II (Acute Physiology and
  10. 10. © 2003 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 8 CRITICAL CARE 15 ANTIBIOTICS — 10 Table 5 Antimicrobial Drug Dosages for Treatment of Bacterial Infections in Adults with Normal Renal Function155 Modest Infections* Class of Agent Specific Agent Trade Names Oral Intramuscular Daily Dose Interval Daily Dose Interval Pentids, Crystifor, Pfizerpen, 0.8–3.2 8 hr Penicillin G 6 hr 1.2 million units etc. million units 1.2–2.4 million Penicillin G benzathine — — See fn. 1 Bicillin units Penicillinase-susceptible penicillins 0.6–4.8 million Penicillin G procaine — — 6–24 hr Crysticillin, Duracillin, etc. units 0.8–3.2 Penicillin V Pen-Vee K, V-Cillin K, etc. million units 6 hr — — (0.5–2.0 g) Amoxicillin Amoxil, Larotid, etc. 750–1,500 mg 8 hr — — Ampicillin Omnipen, Polycillin, etc. 1–4 g 6 hr 1–2 g 6 hr Penicillinase-susceptible Azlocillin Azlin — — — — penicillins with activity Geocillin — — Carbenicillin indanyl sodium — — against gram-negative bacilli Mezlocillin Mezlin — — — — Piperacillin Pipracil — — See fn. 3 See fn. 3 Ticarcillin Ticar — — See fn. 4 See fn.4 Cloxacillin Tegopen 1–3 g 6 hr — — Penicillinase-resistant Dicloxacillin Dynapen, Pathocil 1–2 g 6 hr — — penicillins Nafcillin Nafcil, Unipen 2–4 g5 6 hr 2–3 g 4–6 hr Oxacillin Bactocill, Prostaphlin 2–4 g 6 hr 1–2 g 6 hr Amoxicillin-clavulanate Augmentin 750 mg–1.5 g 8 hr — — (amoxicillin) Penicillins with Unasyn — — 1 g (ampicillin) 6 hr Ampicillin-sulbactam β-lactamase inhibitors Piperacillin-tazobactam Zosyn — — — — Ticarcillin-clavulanate Timentin — — — — Cefaclor Ceclor 750 mg–1.5 g 8 hr — — Cefadroxil Duricef, Ultracef 500 mg–2g 12–24 hr — — Cefamandole Mandol — — 2–4 g 6 hr Cefazolin Ancef, Kefzol — — 750 mg–1.5 g 8 hr Cefdinir Omnicef 600 mg 24 hr — — Cefditoren pivoxil Spectracef 200–400 mg 12 hr — — Cefepime Maxipime — — — — Cefixime Suprax 400 mg 24 hr — — Cefmetazole Zefazone — — — — Cefonicid Monocid — — See fn. 7,8 See fn. 7,8 Cefoperazone Cefobid — — See fn. 7,8 See fn. 7,8 Ceforanide Precef — — See fn. 7,8 See fn. 7,8 Cephalosporins Cefotaxime Claforan — — See fn. 7,8 See fn. 7,8 Cefotetan Cefotan — — See fn. 7,8 See fn. 7,8 Cefoxitin Mefoxin — — 2–4 g 6 hr Cefpodoxime Vantin 200–800 mg 12 hr — — Cefprozil Cefzil 500 mg–1 g 12–24 hr — — Ceftazidime Fortaz, Tazidime — — See fn. 7,8 See fn. 7,8 Ceftibutin Cedax 400 mg — — — Ceftizoxime Cefizox — — See fn. 7,8 See fn. 7,8 Ceftriaxone Rocephin — 24 hr See fn. 7,8 See fn. 7,8 Cefuroxime Zinacef, Ceftin (p.o.) 250–500 mg 12 hr See fn. 7,8 See fn. 7,8 Cephalexin Keflex 1–4 g 6 hr — — Cephapirin Cefadyl — — 2–3 g 6 hr Cephradine Anspor, Velosef 1–4 g 6 hr 2g 6 hr Loracarbef Lorabid 400–800 mg 12 hr — — Imipenem-cilastatin Primaxin — — — — Carbapenems Meropenem Merrem — — — — Ertapenem Ivanz — — — — Note: all superscript numbers refer to footnotes following table. (continued ) *Infections of the upper respiratory tract, soft tissues, etc.