The American Journal of Medicine (2005) Vol 118 (7A), 1S 6S

A clinicians guide to the appropriate and accurate use

of antibiotics: the Council for Appropriate and Rational
Antibiotic Therapy (CARAT) criteria
Thomas G. Slama, MD,a Alpesh Amin, MD, MBA,b Stephen A. Brunton, MD,c
Thomas M. File, Jr, MD,d Gary Milkovich, RPh,e Keith A. Rodvold, PharmD,f
Daniel F. Sahm, PhD,g Joseph Varon, MD,h David Weiland, Jr, MD,i for the Council
for Appropriate and Rational Antibiotic Therapy (CARAT)

a
Department of Infectious Diseases, Indiana University School of Medicine, Indiana University, Indianapolis, Indiana, USA;
b
Department of Medicine, University of California, Irvine Medical Center, Orange, California, USA;
c
Department of Family Medicine, Carolinas Medical Center, Charlotte, North Carolina, USA;
d
Department of Internal Medicine, Northeastern Ohio Universities, College of Medicine, Akron, Ohio, USA;
e
RJM and Associates, Woodbridge, Virginia, USA;
f
Colleges of Pharmacy and Medicine, University of Illinois at Chicago, Chicago, Illinois, USA;
g
Focus Technologies, Inc., Herndon, Virginia, USA;
h
The University of Texas Health Sciences Center at Houston, Houston, Texas, USA;
i
Department of Family Medicine, University of South Florida, Largo, Florida, USA.

KEYWORDS: In response to the overuse and misuse of antibiotics, leading to increasing bacterial resistance and
Antibiotic therapy decreasing development of new antibiotics, the Council for Appropriate and Rational Antibiotic
resistance Therapy (CARAT) has developed criteria to guide appropriate and accurate antibiotic selection. The
Antibiotics criteria, which are aimed at optimizing antibiotic therapy, include evidence-based results, therapeutic
Antimicrobials benefits, safety, optimal drug for the optimal duration, and cost-effectiveness.
2005 Elsevier Inc. All rights reserved.

Antibiotics were hailed as miracle drugs after their initial the development of increasing antibiotic resistance among ex-
introduction in the 1940s. Their widespread availability and isting bacterial diseases underscore the continued importance
success led to such dramatic reductions in the morbidity and of treating infectious diseases.
mortality caused by infectious diseases that in 1967 US Sur- Although increased bacterial resistance to antibiotics has
geon General William H. Stewart reportedly declared that it several causes, 2 key factors are the overuse and misuse of
was time to close the book on infectious diseases.1,2 How- antibiotics.3 6 Antibiotics are frequently prescribed for in-
ever, the subsequent emergence of new infectious diseases and dications in which their use is not warranted, or an incorrect
or suboptimal antibiotic is prescribed. Although the popu-
lation- and visit-based prescribing rates for antimicrobials in
Requests for reprints should be addressed to Thomas M. File, Jr., MD,
Internal Medicine Division, Northeastern Ohio Universities, College of
ambulatory care settings declined 23% and 25%, respec-
Medicine, 75 Arch Street, Suite 105, Akron, Ohio 44304. tively, between 1992 and 2000 in the United States, many
E-mail address: [email protected]. prescriptions for antibiotics in ambulatory patients are

0002-9343/$ -see front matter 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2005.05.007
2S The American Journal of Medicine, Vol 118 (7A), July 2005

written to treat acute respiratory tract infections (RTIs), Appropriate antibiotic therapy
including the common cold, acute bronchitis, and acute
uncomplicated rhinosinusitis.79 The first consideration in choosing appropriate antibiotic
The overuse and misuse of antibiotics has contributed to therapy should be whether there is an indication for an
an increase in bacterial resistance patterns, which may differ antimicrobial agent. Indications for an antibiotic include the
by locality.8 In addition, antibiotics are now included in unambiguous demonstration or the strong suspicion that the
many animal feeds, which are given to promote growth in etiologic agent is bacterial. In general, the latter should be
animals not otherwise known to be bacterially infected. based on the signs and symptoms of infection, as well as on
Many of these antibiotics are then ingested by humans other factors, including the age of the patient, the patients
through consuming animal products. Taken together, these medical history, and the presence or absence of comorbidi-
factors enhance the risk of developing strains of bacteria ties. There are several guidelines and appropriate use state-
that are resistant to most common classes of antibiotics. ments in the literature that variably discuss this process.8,9,1319
Furthermore, the development of new antibiotics has Once it is decided that an antibiotic is warranted, accurate
stalled10,11 as a result of (1) fewer novel compounds in the use of the agent should be explored, including examining
pipelines of pharmaceutical companies and (2) decisions issues of resistance, benefits, safety, and cost.
that have been made by the same companies to develop Many of the same factors that go into determining
drugs for chronic conditions such as arthritis, depression, whether or not an etiologic agent is bacterial should also be
pain syndromes, lipid disorders, hypertension, and other considered when selecting an antibiotic. Several groups
have issued specific guidelines on the use of antimicrobials
disorders rather than infectious diseases because of the
for certain disease states. According to guidelines on the
higher potential for profit.12 This may, in turn, lead to a
treatment of community-acquired pneumonia (CAP) issued
situation in which it will be more difficult to combat bac-
by the American Thoracic Society (ATS), factors that
terial infections. Consequently, approaches that preserve the
should be taken into account when choosing an antimicro-
efficacy of currently used antibiotics are needed.
bial include severity of illness, presence of comorbidities,
The US Centers for Disease Control and Prevention
presence of identified clinical risk factors for drug-resistant
(CDC) and the World Health Organization (WHO) are ac-
and unusual pathogens, place of therapy (e.g., outpatient vs.
tively addressing the primary issues associated with the
in hospital), and presence of risk factors for drug-resistant
overuse and/or misuse of antibiotics. Less attention has been
Streptococcus pneumoniae, among others.13
paid, however, to the accurate use of antibiotics, defined as
In the 2000 update of their practice guidelines for the
choosing the correct drug at the correct dose for the correct
management of CAP, the Infectious Diseases Society of
duration of treatment. The available evidence suggests that,
America (IDSA) recommended that, when an etiologic di-
when antibiotic use is warranted, choosing the therapy most
agnosis is established or strongly suspected, the antimicro-
likely to achieve clinical cure and treating for the shortest bial agent that is most cost-effective, least toxic, and most
length of time to achieve clinical and microbiologic efficacy narrow in spectrum should be used. When etiologic diag-
will result in lower incidence of retreatment, as well as a nosis is not available and empiric antibiotic selection is
lower incidence of antibiotic resistance.3,4,8 required, severity of illness, pathogen probabilities, resis-
tance patterns, and comorbid conditions should be consid-
ered.14
The Council for Appropriate and Rational The Sinus Allergy and Health Partnership, a group spon-
Antibiotic Therapy sored by the American Academy of Otolaryngology and
Head and Neck Surgery, among others, has issued guide-
The Council for Appropriate and Rational Antibiotic Ther- lines on the antimicrobial treatment of acute bacterial rhi-
apy (CARAT) is an independent, multidisciplinary panel of nosinusitis that recommend considering severity, rate of
healthcare professionals, clinicians as well as scientists, progression, and recent antibiotic exposure when selecting
established to advocate the appropriate and accurate use of antibiotic therapy.16
antibiotics. CARAT has developed 5 criteria to assist
healthcare providers in selecting the most appropriate and Evidence-based results
accurate treatment regimens (Table 1). These criteria are
designed to help guide healthcare practitioners in using In choosing an antibiotic, clinicians should consider the
antibiotics where they are appropriately indicated. This ar- clinical evidence demonstrating that the drug is clinically
ticle addresses issues of appropriate antibiotic therapy and and microbiologically appropriate, the efficacy of that drug
offers guidelines for the accurate use of antibiotics. It also in well-designed clinical trials, and the antibiotic resistance
presents the rationale for treating infectious diseases with patterns of the local region. Clinicians should then use their
shorter-course therapy using optimal agents when antibiotic professional judgment to choose the optimal antibiotic.
therapy is warranted, thus helping to reduce the develop- Well-conducted, randomized, controlled clinical trials pro-
ment of antibiotic resistance and improve outcomes. vide the highest quality information for making decisions.
Slama et al A Clinicians Guide to the CARAT Criteria 3S

Table 1 Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria
for accurate use of antibiotic therapy

Evidence-based results
Therapeutic benefits
Safety
Cost-effectiveness
Optimal drug dose and duration
Shorter-course, more aggressive therapy

Table 2 American Thoracic Society simplified grading system for ranking evidence
in the treatment of community-acquired pneumonia

Evidence Level Definition

Level I (high) Evidence comes from well-conducted,
randomized, controlled trials.
Level II (moderate) Evidence comes from well-designed,
controlled trials without
randomization (including cohort,
patient series, and case-control
studies).
Level II studies also include any
large case series in which systematic
analysis of disease patterns and/or
microbial etiology was conducted, as
well as reports of new therapies that
were not collected in a randomized
fashion.
Level III (low) Evidence comes from case studies
and expert opinion. In some
instances, therapy recommendations
come from antibiotic susceptibility
data without clinical observations.
Adapted from Am J Respir Crit Care Med.13

Without it, providers may make decisions based on tradition clinical and microbiologic cure, as well as the treatment
and anecdotal experience.20 failures associated with the absence of drug treatment. If
Virtually all professional organizations have developed possible, the clinician should identify the causative patho-
guidelines for evaluating clinical evidence. For example, in gen and use surveillance data on regional antibiotic resis-
formulating guidelines for the treatment of CAP, the ATS tance patterns in selecting the optimal therapeutic agent.
applied a simplified 3-level grading system for the types of When evaluating potential therapeutic choices, data on
evidence used in evaluating medications (Table 2), a tool regional antibiotic resistance patterns should be taken into
that has been gaining widespread professional acceptance.13 consideration. Although antibacterial susceptibility patterns
These guidelines are similar to those recommended by the are based on the results of in vitro tests, they can be used as
IDSA.15 guidelines to minimize the chances of clinical failure.
Therefore, regional resistance patterns should be used to
Therapeutic benefits help direct prescribing practices. If there is substantial re-
sistance to a particular class of antibiotics in a particular
The key to applying evidence-based results and making geographic area, a different class of drug should be consid-
appropriate therapeutic choices for each patient involves ered.8,14
determining the correct diagnosis and analyzing the thera-
peutic benefits of possible treatments. To maximize patient
health and reduce unnecessary prescribing, the therapeutic Safety
benefits of each drug should be considered relative to the
status of the patients infection. The clinician must consider In treating patients with a particular drug, safety must be
any evidence that a particular antibiotic can result in a weighed against efficacy. Clinically applicable treatment
4S The American Journal of Medicine, Vol 118 (7A), July 2005

strategies should be chosen to maximize efficacy while They include the potential for reduced occurrence of ad-
minimizing side effects. verse effects, increased patient adherence, decreased pro-
Although antibiotics are generally considered safe and motion of resistance, and decreased costs.22
well tolerated, they have been associated with a wide range The rational use of medicines has been defined by the
of adverse effects. Safety profiles vary for different classes WHO as requiring that patients receive medications appro-
of antibiotics, as well as for antibacterial agents within each priate to their clinical needs, in doses that meet their own
class. In addition, it should be considered that the safety requirements, for an adequate time, and at the lowest cost to
profiles of newer medications may not be as well estab- them and their community.23 As part of its guidelines, the
lished as those that have been in use for many years. In a WHO has recognized that antimicrobial resistance has be-
study of the period between 1975 and 2000, 548 new chem- come a serious worldwide public health problem and has
ical entities were approved for use in the United States; 45 formulated a global strategy of interventions to slow the
of these (8.2%) acquired new black-box warnings and 16 emergence and reduce the spread of antimicrobial-resistant
(2.9%) were withdrawn from the market during this time. microorganisms.
Of the 16 withdrawn from the market, 8 were withdrawn
within 2 years after their introduction. For example, tema- Cost-effectiveness
floxacin was withdrawn 0.3 years after introduction and
grepafloxacin was withdrawn 2.0 years after introduction.21
Choosing inappropriate therapy is associated with increased
In general, the selected antibiotic should be the one that
costs, including the cost of the antibiotic and increases in
satisfies all other criteria and has the lowest rate of known
overall costs of medical care because of treatment failures
adverse events.
and adverse events. Upper RTIs, while usually mild and not
Optimal drug for optimal duration life-threatening, are associated with significant healthcare
costs. Treatment failure results in increased costs, particu-
larly if hospitalization is required.24
Optimal drug selection requires finding the antimicrobial
Using an optimal course of antibiotics can have eco-
class and the specific member of that class that is best suited
nomic as well as clinical advantages. Outpatients may ex-
to treat a particular infection. Because empiric therapy is
perience a faster return to their normal daily routine and an
necessary in most cases, multiple factors have to be consid-
earlier return to work. In a study comparing 500-mg and
ered. Among these are whether the etiologic agent is likely
750-mg intravenous levofloxacin in 232 inpatients with
to be gram-positive or gram-negative, whether a narrow or
CAP (intention-to-treat population), the higher dose of drug
broad-spectrum agent should be chosen, the resistance pat-
was associated with a more rapid intravenous-to-oral switch
terns of the likely pathogen to this drug, both nationally and
(2.35 vs. 2.75 days), fewer doses of oral antibiotic (4.08 vs.
regionally, and the individual patients medical history, in-
8.59 doses), and lower cost of levofloxacin (US$115.47 vs.
cluding recent antibiotic exposure. Several governing bod-
$150.65).25 Other studies have also supported the efficacy
ies, such as the ATS and the IDSA, have issued guidelines
of shorter courses of treatment in pneumonia.26 33 Similar
for the use of antimicrobial therapy in CAP. The IDSA
results have also been found for short courses of therapy for
guidelines for the treatment of outpatients with signs and
bronchitis, sinusitis, and urinary tract infections.34 43
symptoms of CAP suggest considering previous health,
recent courses of antibiotic treatment, and comorbid condi-
tions when determining a treatment.15 Previously healthy
patients with no recent antibiotic therapy should be treated Pharmacokinetic considerations
with a macrolide (erythromycin, azithromycin, or clarithro-
mycin) or doxycycline, whereas previously healthy patients Pharmacokinetic properties differentiate among classes of
recently treated with an antibiotic should be treated with a antibiotics, and even among antibiotics within the same
respiratory fluoroquinolone alone or an advanced macrolide class, in their ability to eradicate bacteria at drug concen-
(azithromycin or clarithromycin) plus high-dose amoxicillin trations attained during therapy.8 Among these properties
or high-dose amoxicillin-clavulanate. Outpatients with co- are the time for which nonprotein-bound serum concentra-
morbiditiesincluding chronic obstructive pulmonary dis- tion of drug exceeds its minimum inhibitory concentration
ease, renal or congestive heart failure, or a malignancy (MIC); the ratio between peak serum concentration (Cmax)
should be treated with an advanced macrolide or a and MIC; and the ratio between drug exposure, measured as
respiratory fluoroquinolone if they had no recent antibiotic area under the serum 24-hour concentration-time curve
therapy or a respiratory fluoroquinolone alone or an ad- (AUC24), and MIC (AUC24MIC) ratio. These parameters
vanced macrolide plus a -lactam if they had a recent have been shown to be coordinated with clinical out-
course of antibiotic therapy.15 come.44 46 For example, at a free-drug AUC24MIC ratio
Optimal duration means prescribing the selected drug for 33.7, the microbiological response of S pneumoniae to
the shortest amount of time required for clinical and micro- fluoroquinolones is 100%.47 An AUC24MIC ratio of 125
biologic efficacy. There are many reasons for reducing an- predicts an 85.4% microbiologic response to levofloxacin
timicrobial therapy to the shortest appropriate duration. and an 81.5% response to ciprofloxacin.48
Slama et al A Clinicians Guide to the CARAT Criteria 5S

For several classes of antibiotics, including the -lactams 7. McCaig LF, Besser RE, Hughes JM. Antimicrobial drug prescription
and macrolides, bacteriologic efficacy can be correlated in ambulatory care settings, United States, 19922000. Emerg Infect
Dis. 2003;9:432 437.
with the time during which drug concentration exceeds 8. Ball P, Baquero F, Cars O, et al. Antibiotic therapy of community
MIC.49,50 Thus, for optimal reduction of bacterial load, respiratory tract infections: strategies for optimal outcomes and minimized
these agents should be administered such that drug concen- resistance emergence. J Antimicrob Chemother. 2002;49:31 40.
trations exceed the MIC for 40% of the dosing interval. 9. Gonzales R, Bartlett JG, Besser RE, et al. Principles of appropriate
In contrast to the time-dependent efficacy of the -lac- antibiotic use for treatment of acute respiratory tract infections in
adults: background, specific aims, and methods. Ann Intern Med.
tams, macrolides, and lincosamides, the aminoglycosides, 2001;134:479 486.
metronidazole, and fluoroquinolones exhibit concentration- 10. Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE, Jr. Trends
dependent bactericidal activity. The efficacy of these drugs in antimicrobial drug development: implications for the future. Clin
has been found to correlate with the CmaxMIC and AUC24 Infect Dis. 2004;38:1279 1286.
MIC ratios.44 46,51 For example, an AUC24MIC ratio of 25 11. Wenzel RP. The antibiotic pipeline challenges, costs, and values.
N Engl J Med. 2004;351:523526.
to 40 is thought to predict optimal bactericidal activity for
12. Infectious Diseases Society of America. Bad bugs, no drugs: as anti-
fluoroquinolones against S pneumoniae.47,49,5254 Thus, for biotic discovery stagnates...a public health crisis brews [IDSA Web
this class of drug, administration of a maximum dose for a site]. IDSA White Paper, July 2004. Available at: http://www.
shorter time would be optimal in the absence of adverse idsociety.org/pa/IDSA_Paper4_final_web.pdf. Accessed August 2,
effects resulting from high drug doses. 2004.
13. Niederman MS, Mandell LA, Anzueto A, et al, for the Ad Hoc
Subcommittee of the Assembly on Microbiology, Tuberculosis, and
Pulmonary Infections. Guidelines for the management of adults with
community-acquired pneumonia: diagnosis, assessment of severity,
Summary antimicrobial therapy, and prevention. Am J Respir Crit Care Med.
2001;163:1730 1754.
Infectious diseases are still a serious problem, com- 14. Bartlett JG, Dowell SF, Mandell LA, File TMJ, Musher DM, Fine MJ,
pounded by the development of antibiotic resistance in for the Infectious Diseases Society of America. Practice guidelines for
many bacteria and the relative lack of newer antimicro- the management of community-acquired pneumonia in adults. Clin
bial agents to combat these multiresistant organisms. In Infect Dis. 2000;31:347382.
choosing appropriate and accurate antibiotic therapy, the 15. Mandell LA, Bartlett JG, Dowell SF, File TM Jr, Musher DM, Whit-
ney C. Update of practice guidelines for the management of commu-
clinician should use the 5 criteria of CARAT described nity-acquired pneumonia in immunocompetent adults. Clin Infect Dis.
herein (evidence-based results, therapeutic benefits, 2003;37:14051433.
safety, optimal drug for the optimal duration, and cost- 16. Anon JB, Jacobs MR, Poole MD, et al. Antimicrobial treatment guide-
effectiveness). Appropriate aggressive short-course lines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg.
treatment is recommended for ensuring clinical and mi- 2004;130(suppl):1 45.
17. Balter MS, La Forge J, Low DE, Mandell L, Grossman RF. Canadian
crobiologic cure, optimal patient adherence, and minimal guidelines for the management of acute exacerbations of chronic
generation of antibiotic resistance. Ideally, institution of bronchitis: executive summary. Can Respir J. 2003;10:248 258.
the 5 CARAT criteria will optimize safe and well-toler- 18. Balter MS, La Forge J, Low DE, Mandell L, Grossman RF. Canadian
ated treatment regimens, curb unnecessary prescribing of guidelines for the management of acute exacerbations of chronic
antibiotics, decrease treatment costs, and increase adher- bronchitis. Can Respir J. 2003;10(suppl B):3B32B.
19. Gonzales R, Bartlett JG, Besser RE, et al. Principles of appropriate
ence.
antibiotic use for treatment of uncomplicated acute bronchitis: back-
ground. Ann Intern Med. 2001;134:521529.
20. Soumerai SB, Avorn J. Principles of educational outreach (academic
detailing) to improve clinical decision making. JAMA. 1990;263:
References 549 556.
21. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM,
1. Patlak M. Book reopened on infectious diseases. US Food & Drug Bor DH. Timing of new black box warnings and withdrawals for
Administration Web site. Available at: http://www.fda.gov/fdac/ prescription medications. JAMA. 2002;287:22152220.
features/396_infe.html. Accessed August 19, 2004. 22. File TM Jr. Judicious use of antibiotics to treat respiratory tract
2. Public Health Service FAQs. The Office of the Public Health Service infections. Curr Opin Infect Dis. 2002;15:149 150.
History Web site. Available at: http://lhncbc.nlm.nih.gov/apdb/ 23. World Health Organization. The Selection and Use of Essential Med-
phsHistory/faqs.html. Accessed August 19, 2004. icines: report of the WHO Expert Committee, 2003 [WHO Web site].
3. Wenzel RP, Edmond MB. Managing antibiotic resistance. N Engl Available at: http://www.who.int/medicines/organization/par/edl/
J Med. 2000;343:19611963. expcom13/unedited_report.doc. Accessed June 24, 2004.
4. Austin DJ, Kristinsson KG, Anderson RM. The relationship between 24. Nicolau D. Clinical and economic implications of antimicrobial resis-
the volume of antimicrobial consumption in human communities and tance for the management of community-acquired respiratory tract
the frequency of resistance. Proc Natl Acad Sci U S A. 1999;96:1152a infections. J Antimicrob Chemother. 2002;50(suppl S1):6170.
1156. 25. Milkovich G, Zadeikis N, Khashab M, Xiang J, Tennenberg AM.
5. Low DE, Pichichero ME, Schaad UB. Optimizing antibacterial therapy Pharmacoeconomic and clinical implications of 750-mg, 5-day levo-
for community-acquired respiratory tract infections in children in an floxacin for community-acquired pneumonia (CAP). Poster presented
era of bacterial resistance. Clin Pediatr. 2004;43:135151. at the 11th International Congress on Infectious Diseases; March 4 7,
6. Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive antibiotic 2004; Cancun, Mexico.
use for acute respiratory infections in the United States. Clin Infect 26. Awunor-Renner C. Length of antibiotic therapy in in-patients with
Dis. 2001;33:757762. primary pneumonias. Ann Trop Med Parasitol. 1979;73:235240.
6S The American Journal of Medicine, Vol 118 (7A), July 2005

27. Sopena N, Martnez-Vzquez C, Rodrguez-Surez JR, Segura F, Va- 40. Mertens JC, van Barneveld PW, Asin HR, et al. Double-blind ran-
lencia A, Sabri M. Comparative study of the efficacy and tolerance of domized study comparing the efficacies and safeties of a short (3-day)
azithromycin versus clarithromycin in the treatment of community- course of azithromycin and a 5-day course of amoxicillin in patients
acquired pneumonia in adults. J Chemother. 2004;16:102103. with acute exacerbations of chronic bronchitis. Antimicrob Agents
28. Agarwal G, Awasthi S, Kabra SK, Kaul A, Singhi S, Walter SD, and Chemother. 1992;36:1456 1459.
the ISCAP Study Group. Three-day versus five-day treatment with 41. Buchanan PP, Stephens TA, Leroy B. A comparison of the efficacy of
amoxicillin for non-severe pneumonia in young children: a multicentre telithromycin versus cefuroxime axetil in the treatment of acute bac-
randomised controlled trial [published correction appears in BMJ. terial maxillary sinusitis. Am J Rhinol. 2003;17:369 377.
2004;328:1066]. BMJ. 2004;328:791. 42. Sher LD, McAdoo MA, Bettis RB, Turner MA, Li NF, Pierce PF. A
29. ODoherty B, Muller O, for the Azithromycin Study Group. Random- multicenter, randomized, investigator-blinded study of 5- and 10-day
ized, multicentre study of the efficacy and tolerance of azithromycin
gatifloxacin versus 10-day amoxicillin/clavulanate in patients with
versus clarithromycin in the treatment of adults with mild to moderate
acute bacterial sinusitis. Clin Ther. 2002;24:269 281.
community-acquired pneumonia. Eur J Clin Microbiol Infect Dis.
43. Iravani A, Klimberg I, Briefer C, Munera C, Kowalsky SF, Echols
1998;17:828 833.
RM. A trial comparing low-dose, short-course ciprofloxacin and stan-
30. Bohte R, vant Wout JW, Lobatto S, et al. Efficacy and safety of
dard 7 day therapy with co-trimoxazole or nitrofurantoin in the treat-
azithromycin versus benzylpenicillin or erythromycin in community-
acquired pneumonia. Eur J Clin Microbiol Infect Dis. 1995;14:182 ment of uncomplicated urinary tract infection. J Antimicrob Che-
187. mother. 1999;43(suppl A):6775.
31. Tellier G, Chang JR, Asche CV, Lavin B, Stewart J, Sullivan SD. 44. Preston SL, Drusano GL, Berman AL, et al. Pharmacodynamics of
Comparison of hospitalization rates in patients with community-ac- levofloxacin: a new paradigm for early clinical trials. JAMA. 1998;
quired pneumonia treated with telithromycin for 5 or 7 days or clar- 279:125129.
ithromycin for 10 days. Curr Med Res Opin. 2004;20:739 747. 45. Forrest A, Nix DE, Ballow CH, Goss TF, Birmingham MC, Schentag
32. Dunbar LM, Wunderink RG, Habib MP, et al. High-dose, short-course JJ. Pharmacodynamics of intravenous ciprofloxacin in seriously ill
levofloxacin for community-acquired pneumonia: a new treatment patients. Antimicrob Agents Chemother. 1993;37:10731081.
paradigm. Clin Infect Dis. 2003;37:752760. 46. Highet VS, Forrest A, Ballow CH, Schentag JJ. Antibiotic dosing
33. Dunbar LM, Khashab MM, Kahn JB, Zadeikis N, Xiang JX, Tennen- issues in lower respiratory tract infection: population-derived area
berg AM. Efficacy of 750-mg, 5-day levofloxacin in the treatment of under inhibitory curve is predictive of efficacy. J Antimicrob Che-
community-acquired pneumonia caused by atypical pathogens. Curr mother. 1999;43:55 63.
Med Res Opin. 2004;20:555563. 47. Ambrose PG, Grasela DM, Grasela TH, Passarell J, Mayer HB, Pierce
34. Wilson R, Allegra L, Huchon G, et al, and the MOSAIC Study Group. PF. Pharmacodynamics of fluoroquinolones against Streptococcus
Short-term and long-term outcomes of moxifloxacin compared to stan- pneumoniae in patients with community-acquired respiratory tract
dard antibiotic treatment in acute exacerbations of chronic bronchitis. infections. Antimicrob Agents Chemother. 2001;45:27932797.
Chest. 2004;125:953964. 48. MacGowan AP, Wootton M, Holt HA. The antibacterial efficacy of
35. Nalepa P, Dobryniewska M, Busman T, Notario G. Short-course levofloxacin and ciprofloxacin against Pseudomonas aeruginosa as-
therapy of acute bacterial exacerbation of chronic bronchitis: a double- sessed by combining antibiotic exposure and bacterial susceptibility. J
blind, randomized, multicenter comparison of extended-release versus Antimicrob Chemother. 1999;43:345349.
immediate-release clarithromycin. Curr Med Res Opin. 2003;19:411
49. Andes D. Pharmacokinetic and pharmacodynamic properties of anti-
420.
microbials in the therapy of respiratory tract infections. Curr Opin
36. Castaldo RS, Celli BR, Gomez F, LaVallee N, Souhrada J, Hanrahan
Infect Dis. 2001;14:165172.
JP. A comparison of 5-day courses of dirithromycin and azithromycin
50. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for
in the treatment of acute exacerbations of chronic obstructive pulmo-
antibacterial dosing of mice and men. Clin Infect Dis. 1998;26:110.
nary disease. Clin Ther. 2003;25:542557.
37. DeAbate CA, Russell M, McElvaine P, et al. Safety and efficacy of 51. Schentag JJ, Nix DE, Forrest A, Adelman MH. AUICthe universal
oral levofloxacin versus cefuroxime axetil in acute bacterial exacer- parameter within the constraint of a reasonable dosing interval. Ann
bations of chronic bronchitis. Respir Care. 1997;42:206 213. Pharmacother. 1996;30:1029 1031.
38. Langan CE, Zuck P, Vogel F, et al. Randomized, double-blind study of 52. Weiss K, Restieri C, Gauthier R, et al. A nosocomial outbreak of
short-course (5 day) grepafloxacin versus 10 day clarithromycin in fluoroquinolone-resistant Streptococcus pneumoniae. Clin Infect Dis.
patients with acute bacterial exacerbations of chronic bronchitis. J 2001;33:517522.
Antimicrob Chemother. 1999;44:515523. 53. Wright DH, Brown GH, Peterson ML, Rotschafer JC. Application of
39. Henry D, Ruoff GE, Rhudy J, et al. Effectiveness of short-course fluoroquinolone pharmacodynamics. J Antimicrob Chemother. 2000;
therapy (5 days) with cefuroxime axetil in treatment of secondary 46:669 683.
bacterial infections of acute bronchitis. Antimicrob Agents Chemother. 54. Woodnutt G. Pharmacodynamics to combat resistance. J Antimicrob
1995;39:2528 2534. Chemother 2000;46(suppl T1):2531.