Original Article
Brief Report
Resistance to Levofloxacin and Failure of Treatment of Pneumococcal Pneumonia
N Engl J Med 2002; 346:747-750March 7, 2002
- Article
The emergence of Streptococcus pneumoniae that is resistant to the β-lactam and macrolide antimicrobial drugs has aroused concern about the use of these agents for the empirical treatment of community-acquired pneumonia.1 Fluoroquinolones with increased activity against S. pneumoniae, such as levofloxacin, moxifloxacin, and gatifloxacin, are now being recommended for the treatment of patients with community-acquired pneumonia whose infection is likely to have been caused by multidrug-resistant strains.1-6 However, there has been relatively little experience with the use of these agents, as compared with the β-lactam and macrolide antimicrobial agents, as monotherapy for community-acquired pneumonia.
We describe four patients with pneumococcal pneumonia in whom empirical treatment with oral levofloxacin failed. In all four cases, an organism that either was resistant to levofloxacin before therapy or acquired resistance during therapy was isolated. In the light of these failures, we investigated the use of antimicrobial agents according to prescription records and determined the frequency of routine testing for pneumococcal susceptibility to levofloxacin in clinical laboratories in Ontario.
Case Reports
Patient 1
Patient 1 was a 64-year-old man from Nova Scotia who presented in the late winter of 2000 with a two-day history of productive cough, fatigue, dyspnea, and fever (temperature, 38.4°C). He had no history of treatment with fluoroquinolones. The clinical findings were compatible with the presence of a right-sided pneumonia. A sputum specimen contained gram-positive diplococci and grew S. pneumoniae that was susceptible to levofloxacin. He was treated for community-acquired pneumonia with 500 mg of oral levofloxacin daily for 10 days. The day after his last dose was given, signs and symptoms of recurrent pneumonia developed. Another sputum culture grew S. pneumoniae, which was now resistant to levofloxacin (Table 1Table 1
Microbiologic Characteristics of Streptococcus pneumoniae Isolated before, during, or after Therapy with Oral Levofloxacin from Four Patients with Community-Acquired Pneumonia.).Patient 2
Patient 2 was a 37-year-old woman from Nova Scotia who presented to the emergency department in the spring of 2000 with cough and fever (temperature, 38.7°C). She had no history of treatment with fluoroquinolones. A radiograph of the chest revealed consolidation in the right middle lobe. A sputum specimen showed gram-positive diplococci and grew S. pneumoniae with susceptibility to levofloxacin according to the disk-diffusion method. She was treated for community-acquired pneumonia with 500 mg of oral levofloxacin daily. On the third day of treatment, her clinical condition had not improved, and repeated radiography of the chest showed progression of the infiltrates. Another sputum specimen contained gram-positive diplococci and grew S. pneumoniae, which was now resistant to levofloxacin (Table 1).
Patient 3
Patient 3 was a 66-year-old woman from Ontario who was admitted to the hospital because of community-acquired pneumonia. She had a history of chronic obstructive lung disease, allergy to penicillin, and chronic lymphocytic leukemia, which did not currently require treatment. She had received a 10-day course of ciprofloxacin 6 months earlier and a 10-day course of oral levofloxacin 1 month previously, both for the treatment of an acute exacerbation of chronic bronchitis.
Two weeks before admission, an upper respiratory tract infection developed. Eight days before admission, treatment with 500 mg of ciprofloxacin twice daily was begun because of her persistent respiratory symptoms. At the time of admission, her clinical condition had deteriorated, and she was found to have an infiltrate in the right lower and middle lobes and a small right-sided pleural effusion. Blood cultures grew S. pneumoniae. Treatment was switched to 500 mg of oral levofloxacin daily. Cultures of pleural fluid obtained on the fourth hospital day grew S. pneumoniae. On the fifth hospital day, septic shock developed. The patient was intubated and transferred to the intensive care unit. She died the following day. Testing of the isolates for susceptibility to the fluoroquinolones was not performed at the time of admission, since such testing was not routine. On subsequent susceptibility testing, however, the initial isolate was found to be resistant to levofloxacin (Table 1).
Patient 4
Patient 4 was an 80-year-old woman from British Columbia who presented to her doctor in the summer of 2001 with signs and symptoms of an acute exacerbation of chronic bronchitis. She had a history of chronic obstructive lung disease. Treatment was begun with 500 mg of ciprofloxacin twice daily. After six days of therapy, she returned to her physician because her symptoms had not improved. A radiograph of the chest showed changes compatible with the development of pneumonia, and treatment with 500 mg of oral levofloxacin daily was begun. After eight days of therapy, her condition still had not improved, and treatment was switched to a macrolide antimicrobial agent. Sputum cultures grew S. pneumoniae that was resistant to levofloxacin (Table 1).
Methods
Susceptibility testing was performed on a pair of isolates from each patient according to the guidelines of the National Committee for Clinical Laboratory Standards.7 All the isolates were serotyped at the National Centre for Streptococcus (Edmonton, Alta., Canada). The isolates were also examined by pulsed-field gel electrophoresis after the digestion of bacterial DNA with SmaI, according to methods described by Murray et al.8 Amplification of the parC and gyrA genes and DNA sequencing were performed as previously described, as was the determination of active efflux (a mechanism of resistance mediated by a membrane protein that transports levofloxacin out of the cell).9
After the death of Patient 3, the Quality Management Program–Laboratory Services of the Ontario Medical Association deemed it necessary to determine how frequently laboratories were performing routine testing of the susceptibility of pneumococci to levofloxacin. In the fall of 2000, we sent a pure culture of S. pneumoniae from a patient with community-acquired pneumonia to 109 participating laboratories in Ontario for blinded assessment of the proficiency of each laboratory in identifying the organism. The Quality Management Program–Laboratory Services promulgates the standards of the National Committee for Clinical Laboratory Standards in microbiology. IMS Health (Montreal) provided an estimate of the total number of prescriptions for antimicrobial agents dispensed in Canadian retail pharmacies.
Results
Each of the two isolates from Patients 1, 2, and 3 had the same pattern on pulsed-field gel electrophoresis and the same serotype, but the pattern and serotype of the isolates differed among the patients (Table 1). The results of DNA sequencing of the fluoroquinolone-resistance–determining region of the parC and gyrA genes are shown in Table 1. All the isolates were susceptible to penicillin and erythromycin. Active efflux did not contribute to the reduced fluoroquinolone susceptibility observed in any of the isolates.
According to the results of the Quality Management Program–Laboratory Services survey, all 109 laboratories correctly identified the challenge organism as S. pneumoniae. However, only 15 of these laboratories performed levofloxacin-susceptibility testing.
Levofloxacin was approved for use in Canada in the fall of 1997. In 1998, 51,908 prescriptions for oral levofloxacin were written for adults; in 1999 this number increased to 161,277, and in 2000 it increased to 316,467. In 2000, 1.3 levofloxacin prescriptions per 100 persons were written, as compared with 14.7 prescriptions for macrolides per 100 persons and 6.2 prescriptions for amoxicillin–clavulanate or second-generation cephalosporins per 100 persons.
Discussion
In the treatment of pneumococcal pneumonia with β-lactam, tetracycline, and macrolide antimicrobial drugs, pneumococcal resistance usually results from the acquisition of a resistance gene before therapy. However, reduced susceptibility or resistance to the fluoroquinolones may develop during therapy. Such a change could adversely affect the pharmacodynamics of the drug. As the prevalence of resistant pneumococci increases, so does the likelihood that treatment will fail if susceptibility testing is not performed. In our opinion, the current data indicate that recent exposure to a fluoroquinolone should be a contraindication to the use of another fluoroquinolone for the empirical treatment of community-acquired pneumonia. Finally, other risk factors for infection with a resistant strain may need to be taken into consideration before one of these agents is prescribed.10
Decreased susceptibility to the fluoroquinolones develops primarily as a result of mutations in the parC and gyrA genes, which encode the targets of fluoroquinolones, the topoisomerase enzymes.11 These spontaneous mutations occur at a frequency of 1 in 106 to 1 in 109. This is analogous to the development of resistance to rifampin and streptomycin in Mycobacterium tuberculosis, which occurs as a result of mutations in the rpoB and str genes, the genes that encode the respective target proteins.12 In patients with pneumonia, there may be more than 1010 infecting organisms in the lung parenchyma.13,14 Thus, not only may a fluoroquinolone-resistant strain of pneumococcus be acquired from another person (as in cases of primary resistance),15 but resistance may also develop during treatment or as a result of previous fluoroquinolone exposure (as in cases of acquired resistance). Acquired resistance probably explains the resistance to levofloxacin in Patients 1 and 2 in this report. The ratio of the peak concentration to the minimal inhibitory concentration (MIC) for the infecting pathogen or the ratio of the area under the concentration–time curve (AUC) to the MIC has been directly linked to the probability of a successful clinical or microbiologic outcome in S. pneumoniae infections when the ratio is greater than 30.16,17 The AUC:MIC ratio may have been as low as 6 in Patient 1 and as low as 3 in Patients 2, 3, and 4.18
In some countries, there have been reports suggesting that fluoroquinolone resistance in S. pneumoniae may be increasing,19,20 but in the United States, the incidence of such resistance remains below 1 percent.21 Therefore, the National Committee for Clinical Laboratory Standards does not recommend that levofloxacin, moxifloxacin, or gatifloxacin be included in the routine panel of agents used in susceptibility testing of pneumococci.7 According to the results of the assessment of proficiency of 109 laboratories in Ontario, laboratories in that province are not routinely performing fluoroquinolone-susceptibility testing. Since fluoroquinolones are being recommended in some situations for the empirical treatment of community-acquired pneumonia, it may now be appropriate to consider recommending routine testing and reporting of the susceptibility of pneumococci to these agents. Although routine testing reliably detects high-level resistance to levofloxacin, it may not always detect low-level resistance, such as that in Patient 2.9,22
Since S. pneumoniae can develop resistance to fluoroquinolones during therapy and since cross-resistance to other fluoroquinolones is likely to occur,19 physicians should be aware of the consequences of substituting one fluoroquinolone compound for another if a patient does not have a response to the initial therapy, as was the case for Patients 3 and 4. In a case–control study by Ho et al.,10 it was found that the presence of chronic obstructive lung disease, a nosocomial origin of the bacteria, residence in a nursing home, and exposure to fluoroquinolones were all independently associated with colonization or infection by levofloxacin-resistant pneumococci. Ironically, it is for patients with these same factors that fluoroquinolones are recommended as first-line therapy.3 None of the position papers published on community-acquired pneumonia since the introduction of fluoroquinolones for the treatment of pneumococcal pneumonia have suggested that a history of fluoroquinolone use should be a reason for caution in using one of these antimicrobials.1-4
The volume of levofloxacin consumed in Canada is small in comparison with the volume of other agents used to treat lower respiratory tract infections. Nevertheless, we identified four patients in whom resistance to fluoroquinolones was associated with the failure of bacterial eradication and the lack of a clinical response. This finding suggests that routine testing of pneumococci for susceptibility to fluoroquinolones should now be considered. Such testing would identify patients who are infected with a resistant strain, although physicians should be aware that resistance may develop during therapy.
Supported in part by a grant from the Canadian Bacterial Diseases Network.
Source Information
From Queen Elizabeth Health Sciences Centre, Halifax, N.S. (R.D.); University Health Network, Toronto (R.C., J.L.B., D.E.L.); Toronto Medical Laboratories and the Department of Microbiology, Mount Sinai Hospital, Toronto (J.L.B., D.J.B., J.C.S.A., D.E.L.); the University of Toronto, Toronto (R.C., J.L.B., D.J.B., J.C.S.A., D.E.L.); Victoria General Hospital, Victoria, B.C. (P.K.); and the Quality Management Program–Laboratory Services, Ontario Medical Association, Toronto (C.F., D.E.L.) — all in Canada.
Address reprint requests to Dr. Low at the Department of Microbiology, Mount Sinai Hospital, 600 University Ave., Rm. 1487, Toronto, ON M5G 1X5, Canada, or at dlow@mtsinai.on.ca.
- References
References
1
Bartlett JG ,Dowell SF ,Mandell LA ,File TM Jr ,Musher DM ,Fine MJ . Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis 2000;31:347-382
CrossRef | Medline2
Niederman MS ,Mandell LA ,Anzueto A , et al. Guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 2001;163:1730-1754
Web of Science | Medline3
Mandell LA ,Marrie TJ ,Grossman RF ,Chow AW ,Hyland RH . Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin Infect Dis 2000;31:383-421
CrossRef | Medline4
Heffelfinger JD ,Dowell SF ,Jorgensen JH , et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. Arch Intern Med 2000;160:1399-1408
CrossRef | Web of Science | Medline5
File TM Jr ,Segreti J ,Dunbar L , et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother 1997;41:1965-1972
Web of Science | Medline6
Petitpretz P, Arvis P, Marel M, Moita J, Urueta J, CAP5 Moxifloxacin Study Group
CrossRef | Web of Science | Medline7
Performance standards for antimicrobial susceptibility testing: eleventh informational supplement. Wayne, Pa.: National Committee for Clinical Laboratory Standards, 2001. (NCCLS document no. M100-S11.)
8
Murray BE ,Singh KV ,Heath JD ,Sharma BR ,Weinstock GM . Comparison of genomic DNAs of different enterococcal isolates using restriction endonucleases with infrequent recognition sites. J Clin Microbiol 1990;28:2059-2063[Erratum, J Clin Microbiol 1991;29:418.]
Web of Science | Medline9
Bast DJ ,Low DE ,Duncan CL , et al. Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae: contributions of type II topoisomerase mutations and efflux to levels of resistance. Antimicrob Agents Chemother 2000;44:3049-3054
CrossRef | Web of Science | Medline10
Ho PL ,Tse WS ,Tsang KW , et al. Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study. Clin Infect Dis 2001;32:701-707
CrossRef | Web of Science | Medline11
Hooper DC . Mechanisms of action of antimicrobials: focus on fluoroquinolones. Clin Infect Dis 2001;32:Suppl 1:S9-S15
CrossRef | Web of Science | Medline12
Van Rie AA ,Warren R ,Mshanga I , et al. Analysis for a limited number of gene codons can predict drug resistance of Mycobacterium tuberculosis in a high-incidence community. J Clin Microbiol 2001;39:636-641
CrossRef | Web of Science | Medline13
Frisch AW ,Tripp JT ,Barrett CD Jr ,Pidgeon BE . The specific polysaccharide content of pneumonic lungs. J Exp Med 1942;76:505-510
CrossRef | Web of Science | Medline14
Monso E ,Ruiz J ,Rosell A , et al. Bacterial infection in chronic obstructive pulmonary disease: a study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med 1995;152:1316-1320
Web of Science | Medline15
Weiss K ,Restieri C ,Gauthier R , et al. A nosocomial outbreak of fluoroquinolone-resistant Streptococcus pneumoniae. Clin Infect Dis 2001;33:517-522
CrossRef | Web of Science | Medline16
Lister PD ,Sanders CC . Pharmacodynamics of trovafloxacin, ofloxacin, and ciprofloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model. Antimicrob Agents Chemother 1999;43:1118-1123
Web of Science | Medline17
Preston SL ,Drusano GL ,Berman AL , et al. Pharmacodynamics of levofloxacin: a new paradigm for early clinical trials. JAMA 1998;279:125-129
CrossRef | Web of Science | Medline18
Chien SC ,Rogge MC ,Gisclon LG , et al. Pharmacokinetic profile of levofloxacin following once-daily 500-milligram oral or intravenous doses. Antimicrob Agents Chemother 1997;41:2256-2260
Web of Science | Medline19
Chen DK ,McGeer A ,de Azavedo JC ,Low DE . Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N Engl J Med 1999;341:233-239
Full Text | Web of Science | Medline20
Ho PL ,Que TL ,Tsang DN ,Ng TK ,Chow KH ,Seto WH . Emergence of fluoroquinolone resistance among multiply resistant strains of Streptococcus pneumoniae in Hong Kong. Antimicrob Agents Chemother 1999;43:1310-1313
Web of Science | Medline21
Sahm DF ,Peterson DE ,Critchley IA ,Thornsberry C . Analysis of ciprofloxacin activity against Streptococcus pneumoniae after 10 years of use in the United States. Antimicrob Agents Chemother 2000;44:2521-2524
CrossRef | Web of Science | Medline22
Richardson DC ,Bast D ,McGeer A ,Low DE . Evaluation of susceptibility testing to detect fluoroquinolone resistance mechanisms in Streptococcus pneumoniae. Antimicrob Agents Chemother 2001;45:1911-1914
CrossRef | Web of Science | Medline
- Citing Articles (173)
Citing Articles
1
Roland Leclercq, Rafael Cantón, Derek F.J. Brown, Christian G. Giske, Peter Heisig, Alasdair P. MacGowan, Johan W. Mouton, Patrice Nordmann, Arne C. Rodloff, Gian Maria Rossolini, Claude-James Soussy, Martin Steinbakk, Trevor G. Winstanley, Gunnar Kahlmeter. (2011) EUCAST Expert Rules in Antimicrobial Susceptibility Testing. Clinical Microbiology and Infectionno-no
CrossRef2
J.-S. SONG, P.-G. CHOE, K.-H. SONG, W.-B. PARK, S.-W. PARK, H.-B. KIM, M.-D. OH, E.-C. KIM, N.-J. KIM. (2011) Risk factors for 30-day mortality in adult patients with pneumococcal bacteraemia, and the impact of antimicrobial resistance on clinical outcomes. Epidemiology and Infection1-10
CrossRef3
Vicenç Falcó, Ana Sánchez, Albert Pahissa, Jordi Rello. (2011) Emerging drugs for pneumococcal pneumonia. Expert Opinion on Emerging Drugs 16:3, 459-477
CrossRef4
S. K. Glass, D. L. Pearl, S. A. McEwen, R. Finley. (2010) A province-level risk factor analysis of fluoroquinolone consumption patterns in Canada (2000-06). Journal of Antimicrobial Chemotherapy 65:9, 2019-2027
CrossRef5
Jae-Hoon Song, Doo Ryeon Chung. (2010) Respiratory Infections Due to Drug-Resistant Bacteria. Infectious Disease Clinics of North America 24:3, 639-653
CrossRef6
Frédéric Lamoth, Gilbert Greub. (2010) Fastidious intracellular bacteria as causal agents of community-acquired pneumonia. Expert Review of Anti-infective Therapy 8:7, 775-790
CrossRef7
Rafael Cantón. (2010) Lectura interpretada del antibiograma: una necesidad clínica. Enfermedades Infecciosas y Microbiología Clínica 28:6, 375-385
CrossRef8
D. Orr, P. Wilkinson, L. Moyce, S. Martin, R. George, B. Pichon. (2010) Incidence and epidemiology of levofloxacin resistance in Streptococcus pneumoniae: experience from a tertiary referral hospital in England. Journal of Antimicrobial Chemotherapy 65:3, 449-452
CrossRef9
Jeffrey N. Weiser. (2010) The pneumococcus: why a commensal misbehaves. Journal of Molecular Medicine 88:2, 97-102
CrossRef10
Joseph M. Blondeau. (2009) New concepts in antimicrobial susceptibility testing: the mutant prevention concentration and mutant selection window approach. Veterinary Dermatology 20:5-6, 383-396
CrossRef11
Tom van der Poll, Steven M Opal. (2009) Pathogenesis, treatment, and prevention of pneumococcal pneumonia. The Lancet 374:9700, 1543-1556
CrossRef12
Y-C. Hsieh, L-Y. Chang, Y-C. Huang, H-C. Lin, L-M. Huang, P-R. Hsueh. (2009) Circulation of international clones of levofloxacin non-susceptible Streptococcus pneumoniae in Taiwan. Clinical Microbiology and Infection
CrossRef13
Annie Wong-Beringer, Lee H Nguyen, Michelle Lee, Kimberly A Shriner, Jean Pallares. (2009) An Antimicrobial Stewardship Program with a Focus on Reducing Fluoroquinolone Overuse. Pharmacotherapy 29:6, 736-743
CrossRef14
Jerónimo Pachón, Juan De Dios Alcántara Bellón, Elisa Cordero Matía, Ángela Camacho Espejo, Carmen Lama Herrera, Antonio Rivero Román. (2009) Estudio y tratamiento de las neumonías de adquisición comunitaria en adultos. Medicina Clínica 133:2, 63-73
CrossRef15
(2008) Position Paper: Recommended Design Features of Future Clinical Trials of Antibacterial Agents for Community‐Acquired Pneumonia. Clinical Infectious Diseases 47:S3, S249-S265
CrossRef16
Hubert Chardon. (2008) L’antibiogramme du pneumocoque. Revue Francophone des Laboratoires 2008:407, 45-59
CrossRef17
S. Le Hello, S. Page, B. Garin. (2008) Fluoroquinolone resistance in a clinical isolate of Streptococcus pneumoniae in the South Pacific. International Journal of Antimicrobial Agents 32:1, 91-92
CrossRef18
Marc Miravitlles, Antonio Anzueto. (2008) Moxifloxacin: a respiratory fluoroquinolone. Expert Opinion on Pharmacotherapy 9:10, 1755-1772
CrossRef19
Patrick G. P. Charles, Michael Whitby, Andrew J. Fuller, Robert Stirling, Alistair A. Wright, Tony M. Korman, Peter W. Holmes, Keryn J. Christiansen, Grant W. Waterer, Robert J. P. Pierce, Barrie C. Mayall, John G. Armstrong, Michael G. Catton, Graeme R. Nimmo, Barbara Johnson, Michelle Hooy, M. L. Grayson, . (2008) The Etiology of Community‐Acquired Pneumonia in Australia: Why Penicillin plus Doxycycline or a Macrolide Is the Most Appropriate Therapy. Clinical Infectious Diseases 46:10, 1513-1521
CrossRef20
Hartmut M Lode, Malina Schmidt-Ionas, Ralf Stahlmann. (2008) Gemifloxacin for community-acquired pneumonia. Expert Opinion on Investigational Drugs 17:5, 779-786
CrossRef21
Anne von Gottberg, Keith P Klugman, Cheryl Cohen, Nicole Wolter, Linda de Gouveia, Mignon du Plessis, Ruth Mpembe, Vanessa Quan, Andrew Whitelaw, Rena Hoffmann, Nelesh Govender, Susan Meiring, Anthony M Smith, Stephanie Schrag. (2008) Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study. The Lancet 371:9618, 1108-1113
CrossRef22
Jae Kyun Hur. (2008) The use of fluoroquinolone in children. Korean Journal of Pediatrics 51:10, 1042
CrossRef23
Félix Gutiérrez, Mar Masiá. (2008) Improving Outcomes of Elderly Patients with Community-Acquired Pneumonia. Drugs & Aging 25:7, 585-610
CrossRef24
Silvano Esposito, Marco Fiore. (2007) Community-acquired pneumonia: is it time to shorten the antibiotic treatment?. Expert Review of Anti-infective Therapy 5:6, 933-938
CrossRef25
Thomas M File. 2007. Impact of Guidelines on Antimicrobial Treatment of Respiratory Tract Infections. , 371-396.
CrossRef26
Jonathan Z. Li, Lisa G. Winston, Dan H. Moore, Stephen Bent. (2007) Efficacy of Short-Course Antibiotic Regimens for Community-Acquired Pneumonia: A Meta-analysis. The American Journal of Medicine 120:9, 783-790
CrossRef27
Ross J. Davidson, Roberto Melano, Kevin R. Forward. (2007) Antimicrobial resistance among invasive isolates of Streptococcus pneumoniae collected across Canada. Diagnostic Microbiology and Infectious Disease 59:1, 75-80
CrossRef28
S. K. Olofsson, O. Cars. (2007) Optimizing Drug Exposure to Minimize Selection of Antibiotic Resistance. Clinical Infectious Diseases 45:Supplement 2, S129-S136
CrossRef29
J. Lopez Sisniega, Milan Profant, Rom Kostrica, Hetty Waskin. (2007) Oral Garenoxacin in the Treatment of Acute Bacterial Maxillary Sinusitis: A Phase II, Multicenter, Noncomparative, Open-Label Study in Adult Patients Undergoing Sinus Aspiration. Clinical Therapeutics 29:8, 1632-1644
CrossRef30
Salvador Bello Dronda, Manuel Vilá Justribó. (2007) ¿Seguiremos teniendo antibióticos mañana?. Archivos de Bronconeumología 43:8, 450-459
CrossRef31
2007. Identifying Drug-Resistant Bacterial Infections: Opportunity and Activity in the Diagnostics Arena. .
CrossRef32
Daniel Hart, Melvin P. Weinstein. (2007) Cross-over assessment of serum bactericidal activity of moxifloxacin and levofloxacin versus penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in healthy volunteers. Diagnostic Microbiology and Infectious Disease 58:3, 375-378
CrossRef33
K. Drlica, X. Zhao. (2007) Mutant Selection Window Hypothesis Updated. Clinical Infectious Diseases 44:5, 681-688
CrossRef34
David J. Vaughan, Glenn S. Tillotson, Keith P. Klugman. (2007) Streptococcus pneumoniae. Infectious Diseases in Clinical Practice 15:2, 92-99
CrossRef35
L. A. Mandell, R. G. Wunderink, A. Anzueto, J. G. Bartlett, G. D. Campbell, N. C. Dean, S. F. Dowell, T. M. File, D. M. Musher, M. S. Niederman, A. Torres, C. G. Whitney. (2007) Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 44:Supplement 2, S27-S72
CrossRef36
Michael B Kays, George G Zhanel, Megan A Reimann, Judi Jacobi, Gerald A Denys, David W Smith, Matthew F Wack. (2007) Selection of a gyrA Mutation and Treatment Failure with Gatifloxacin in a Patient with Streptococcus pneumoniae with a Preexisting parC Mutation. Pharmacotherapy 27:2, 221-226
CrossRef37
2007. P. , 150-175.
CrossRef38
J.M. Querol-Ribelles, J. Molina, K. Naberan, E. Esteban, A. Herreras, J. Garcia-de-Lomas. (2006) Discrepancy between antibiotics administered in acute exacerbations of chronic bronchitis and susceptibility of isolated pathogens in respiratory samples: multicentre study in the primary care setting. International Journal of Antimicrobial Agents 28:5, 472-476
CrossRef39
Robert Cohen. (2006) Approaches to Reduce Antibiotic Resistance in the Community. The Pediatric Infectious Disease Journal 25:10, 977-980
CrossRef40
Kristen N. Schurek, Heather J. Adam, Daryl J. Hoban, George G. Zhanel. (2006) Call for the international adoption of microbiological breakpoints for fluoroquinolones and Streptococcus pneumoniae. International Journal of Antimicrobial Agents 28:3, 266-269
CrossRef41
Joseph M Blondeau. (2006) Update on the use of the macrolides for community-acquired respiratory tract infections. Therapy 3:5, 619-650
CrossRef42
J. Garau. (2006) Impact of antibiotic restrictions: the ethical perspective. Clinical Microbiology and Infection 12, 16-24
CrossRef43
Manel Luján, Miguel Gallego, Jordi Rello. (2006) Optimal therapy for severe pneumococcal community-acquired pneumonia. Intensive Care Medicine 32:7, 971-980
CrossRef44
Stephen Brunton. (2006) Overcoming and containing bacterial resistance: appropriate antibiotic use in community-acquired RTIs. Therapy 3:4, 527-533
CrossRef45
F. Alvarez-Lerma, S. Grau, M. Alvarez-Beltran. (2006) Levofloxacin in the treatment of ventilator-associated pneumonia. Clinical Microbiology and Infection 12:s3, 81-92
CrossRef46
J. Carratala, J. E. Martin-Herrero, A. Mykietiuk, C. Garcia-Rey. (2006) Clinical experience in the management of community-acquired pneumonia: lessons from the use of fluoroquinolones. Clinical Microbiology and Infection 12:s3, 2-11
CrossRef47
T. M. File. (2006) Clinical implications and treatment of multiresistant Streptococcus pneumoniae pneumonia. Clinical Microbiology and Infection 12:s3, 31-41
CrossRef48
David Dosa. (2006) Should I Hospitalize My Resident With Nursing Home–Acquired Pneumonia?. Journal of the American Medical Directors Association 7:3, S74-S80
CrossRef49
V. Falcó Ferrer. (2006) Infecciones por neumococo. Medicine - Programa de Formación Médica Continuada Acreditado 9:50, 3266-3273
CrossRef50
Vishakha Sabharwal, Colin D. Marchant. (2006) Fluoroquinolone Use in Children. The Pediatric Infectious Disease Journal 25:3, 257-258
CrossRef51
M. Desrosiers, J-M Klossek, M. Benninger. (2006) Management of acute bacterial rhinosinusitis: current issues and future perspectives. International Journal of Clinical Practice 60:2, 190-200
CrossRef52
L. R. Peterson. (2006) Penicillins for Treatment of Pneumococcal Pneumonia: Does In Vitro Resistance Really Matter?. Clinical Infectious Diseases 42:2, 224-233
CrossRef53
C Andrew DeRyke, Su Young Lee, Joseph L Kuti, David P Nicolau. (2006) Optimising Dosing Strategies of Antibacterials Utilising Pharmacodynamic Principles. Drugs 66:1, 1-14
CrossRef54
Gunnar I Andriesse, Jan Verhoef. (2006) Nosocomial Pneumonia. Treatments in Respiratory Medicine 5:1, 11-30
CrossRef55
J. D. Fuller, A. McGeer, D. E. Low. (2005) Drug-resistant pneumococcal pneumonia: clinical relevance and approach to management. European Journal of Clinical Microbiology & Infectious Diseases 24:12, 780-788
CrossRef56
J. J. Oosterheert, M. J. M. Bonten, M. M. E. Schneider, I. M. Hoepelman. (2005) Predicted effects on antibiotic use following the introduction of British or North American guidelines for community-acquired pneumonia in The Netherlands. Clinical Microbiology and Infection 11:12, 992-998
CrossRef57
David Dosa. (2005) Should I Hospitalize My Resident With Nursing Home–Acquired Pneumonia?. Journal of the American Medical Directors Association 6:5, 327-333
CrossRef58
Fr??d??ric Bert, Latifa Noussair, Nicole Lambert-Zechovsky, Dominique Valla. (2005) Viridans group streptococci: an underestimated cause of spontaneous bacterial peritonitis in cirrhotic patients with ascites. European Journal of Gastroenterology & Hepatology 17:9, 929-933
CrossRef59
Daryl Hoban, Fernando Baquero, Vaughan Reed, David Felmingham. (2005) Demographic analysis of antimicrobial resistance among Streptococcus pneumoniae: worldwide results from PROTEKT 1999–2000. International Journal of Infectious Diseases 9:5, 262-273
CrossRef60
Padmavati Kumashi, Essam Girgawy, Jeffrey J. Tarrand, Kenneth V. Rolston, Issam I. Raad, Amar Safdar. (2005) Streptococcus pneumoniae Bacteremia in Patients With Cancer. Medicine 84:5, 303-312
CrossRef61
E. Purez-Trallero, J. M. Marimon, A. Gonzalez, M. Ercibengoa, J. Larruskain. (2005) In Vivo Development of High-Level Fluoroquinolone Resistance in Streptococcus pneumoniae in Chronic Obstructive Pulmonary Disease. Clinical Infectious Diseases 41:4, 560-564
CrossRef62
Angela E. Bridy-Pappas, Marya B. Margolis, Kimberly J. Center, Daniel J. Isaacman. (2005) Streptococcus pneumoniae : Description of the Pathogen, Disease Epidemiology, Treatment, and Prevention. Pharmacotherapy 25:9, 1193-1212
CrossRef63
M. S. Niederman. (2005) Challenges in the Management of Community-Acquired Pneumonia: The Role of Quinolones and Moxifloxacin. Clinical Infectious Diseases 41:Supplement 2, S158-S166
CrossRef64
S. Sethi. (2005) Moxifloxacin for the Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Clinical Infectious Diseases 41:Supplement 2, S177-S185
CrossRef65
V. T. Andriole. (2005) The Quinolones: Past, Present, and Future. Clinical Infectious Diseases 41:Supplement 2, S113-S119
CrossRef66
Gary V. Doern, Sandra S. Richter, Ashley Miller, Norma Miller, Cassie Rice, Kristopher Heilmann, Susan Beekmann. (2005) Antimicrobial Resistance among Streptococcus pneumoniae in the United States: Have We Begun to Turn the Corner on Resistance to Certain Antimicrobial Classes?. Clinical Infectious Diseases 41:2, 139-148
CrossRef67
B. Wispelwey. (2005) Clinical Implications of Pharmacokinetics and Pharmacodynamics of Fluoroquinolones. Clinical Infectious Diseases 41:Supplement 2, S127-S135
CrossRef68
G. A. Jacoby. (2005) Mechanisms of Resistance to Quinolones. Clinical Infectious Diseases 41:Supplement 2, S120-S126
CrossRef69
David P. Nicolau, Joseph L. Kuti. (2005) Optimizing Antibiotic-Related Outcomes in the Critically Ill Patient. Infectious Diseases in Clinical Practice 13:4, 158-164
CrossRef70
Joseph M Blondeau, Glenn S Tillotson. (2005) Antibiotic dosing: do we dose to cure the individual or do we treat the greater societal needs?. Therapy 2:4, 511-516
CrossRef71
Steven D. Brown, Michael J. Rybak. (2005) Antimicrobial Susceptibility Among Respiratory Tract Pathogens From the Northern States of the USA. Infectious Diseases in Clinical Practice 13:4, 179-186
CrossRef72
J. D. Fuller, D. E. Low. (2005) A Review of Streptococcus pneumoniae Infection Treatment Failures Associated with Fluoroquinolone Resistance. Clinical Infectious Diseases 41:1, 118-121
CrossRef73
Javier Aspa, Olga Rajas, Felipe Rodr??guez de Castro, Antoni Torres. (2005) Current Perspectives on Streptococcus pneumoniae Antibiotic Resistance, With Particular Reference to Isolates From Spain. Clinical Pulmonary Medicine 12:4, 210-219
CrossRef74
C Andrew DeRyke, Dana Maglio, David P Nicolau. (2005) Defining the need for new antimicrobials: clinical and economic implications of resistance in the hospitalised patient. Expert Opinion on Pharmacotherapy 6:6, 873-889
CrossRef75
J. R. Lonks, D. A. Goldmann. (2005) Telithromycin: A Ketolide Antibiotic for Treatment of Respiratory Tract Infections. Clinical Infectious Diseases 40:11, 1657-1664
CrossRef76
Ronald N. Jones, Thomas R. Fritsche, Helio S. Sader. (2005) Therapeutic options among broad-spectrum β-lactams for infections caused by levofloxacin-nonsusceptible Streptococcus pneumoniae. Diagnostic Microbiology and Infectious Disease 52:2, 129-133
CrossRef77
Ana Belén Carlavilla, Francisco López-Medrano, Fernando Chaves, Victoria Villena, José Echave-Sustaeta, José María Aguado. (2005) Fracaso terapéutico de levofloxacino en dos casos de neumonía adquirida en la comunidad complicada con empiema causados por Streptococcus pneumoniae resistente a fluoroquinolonas. Enfermedades Infecciosas y Microbiología Clínica 23:5, 270-273
CrossRef78
O. G. Vanderkooi, D. E. Low, K. Green, J. E. Powis, A. McGeer, . (2005) Predicting Antimicrobial Resistance in Invasive Pneumococcal Infections. Clinical Infectious Diseases 40:9, 1288-1297
CrossRef79
Gary Patou, Glenn Tillotson, Joseph Blondeau. (2005) Management of community-acquired lower respiratory tract infections: gemifloxacin, a new economic paradigm. Therapy 2:3, 357-373
CrossRef80
Stefan Reuter, Winfried V. Kern, Anja Sigge, Hartmut Dohner, Reinhard Marre, Peter Kern, Heike von Baum. (2005) Impact of Fluoroquinolone Prophylaxis on Reduced Infection‐Related Mortality among Patients with Neutropenia and Hematologic Malignancies. Clinical Infectious Diseases 40:8, 1087-1093
CrossRef81
Boji Huang, Steven J. Martin, Kenneth A. Bachmann, Xuming He, James H. Reese, Ying Wei, Cletus Iwuagwu. (2005) A nationwide survey of physician office visits found that inappropriate antibiotic prescriptions were issued for bacterial respiratory tract infections in ambulatory patients. Journal of Clinical Epidemiology 58:4, 414-420
CrossRef82
F. Van Bambeke, J.-M. Michot, J. Van Eldere, P. M. Tulkens. (2005) Quinolones in 2005: an update. Clinical Microbiology and Infection 11:4, 256-280
CrossRef83
Yoichi Hirakata, Katsunori Yanagihara, Yoshitsugu Miyazaki, Kazunori Tomono, Intetsu Kobayashi, Shigeru Kohno. (2005) Antimicrobial susceptibilities of potential bacterial pathogens in adults with acute respiratory tract infections. Diagnostic Microbiology and Infectious Disease 51:4, 271-280
CrossRef84
Rosalind J. Carter, Genevieve Sorenson, Richard Heffernan, Julia A. Kiehlbauch, John S. Kornblum, Robert J. Leggiadro, Lucia J. Nixon, William A. Wertheim, Cynthia G. Whitney, Marcelle Layton, . (2005) Failure To Control an Outbreak of Multidrug‐Resistant Streptococcus pneumoniae in a Long‐Term‐Care Facility: Emergence and Ongoing Transmission of a Fluoroquinolone‐Resistant Strain • . Infection Control and Hospital Epidemiology 26:3, 248-255
CrossRef85
Lionel A. Mandell. (2005) Antimicrobial Resistance and Treatment of Community-Acquired Pneumonia. Clinics in Chest Medicine 26:1, 57-64
CrossRef86
Marc Miravitlles. (2005) Moxifloxacin in respiratory tract infections. Expert Opinion on Pharmacotherapy 6:2, 283-293
CrossRef87
M. Alkorta, M.J. Giménez, D. Vicente, L. Aguilar, E. Pérez-Trallero. (2005) In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point. International Journal of Antimicrobial Agents 25:2, 163-167
CrossRef88
Thomas M. File. (2005) Telithromycin new product overview. Journal of Allergy and Clinical Immunology 115:2, S361-S373
CrossRef89
J. Garau. (2005) Role of beta-lactam agents in the treatment of community-acquired pneumonia. European Journal of Clinical Microbiology & Infectious Diseases 24:2, 83-99
CrossRef90
M. W. R. Pletz, L. McGee, O. Burkhardt, H. Lode, K. P. Klugman. (2005) Ciprofloxacin treatment failure in a patient with resistant Streptococcus pneumoniae infection following prior ciprofloxacin therapy. European Journal of Clinical Microbiology & Infectious Diseases 24:1, 58-60
CrossRef91
Wael E Shams, Martin E Evans. (2005) Guide to Selection of Fluoroquinolones in Patients with Lower Respiratory Tract Infections. Drugs 65:7, 949-991
CrossRef92
David Dosa. (2005) Should I Hospitalize My Resident With Nursing Home???Acquired Pneumonia?. Journal of the American Medical Directors Association 6:5, 327???333
CrossRef93
Michael S. Niederman. (2005) Principles of appropriate antibiotic use. International Journal of Antimicrobial Agents 26, S170-S175
CrossRef94
José Manuel Querol-Ribelles, José María Tenías, José Manuel Querol-Borrás, Teodoro Labrador, Angel Nieto, Damiana González-Granda, Isidoro Martínez. (2005) Levofloxacin versus ceftriaxone plus clarithromycin in the treatment of adults with community-acquired pneumonia requiring hospitalization. International Journal of Antimicrobial Agents 25:1, 75-83
CrossRef95
Glen T Hansen, Joseph M Blondeau. (2005) Mutant prevention concentration as a strategy to minimize antimicrobial resistance: a timely concept but will its acceptance be too late?. Therapy 2:1, 61-66
CrossRef96
Nancy N. Chang, Cynthia K. Murray, Peter M. Houck, Dale W. Bratzler, Claudette Greenway, B. Joseph Guglielmo. (2005) Blood Culture and Susceptibility Results and Allergy History Do Not Influence Fluoroquinolone Use in the Treatment of Community-Acquired Pneumonia. Pharmacotherapy 25:1, 59-66
CrossRef97
Benjamin J Epstein, John G Gums. (2005) Optimal Pharmacological Therapy for Community-Acquired Pneumonia. Drugs 65:14, 1949-1971
CrossRef98
Sujata M. Bhavnani, Jeffrey P. Hammel, Ronald N. Jones, Paul G. Ambrose. (2005) Relationship between increased levofloxacin use and decreased susceptibility of Streptococcus pneumoniae in the United States. Diagnostic Microbiology and Infectious Disease 51:1, 31-37
CrossRef99
Robert C. Owens, Sujata M. Bhavnani, Paul G. Ambrose. (2005) Assessment of pharmacokinetic–pharmacodynamic target attainment of gemifloxacin against Streptococcus pneumoniae. Diagnostic Microbiology and Infectious Disease 51:1, 45-49
CrossRef100
Joshua P. Metlay. (2004) Antibacterial drug resistance: implications for the treatment of patients with community-acquired pneumonia. Infectious Disease Clinics of North America 18:4, 777-790
CrossRef101
Thomas M. File, Michael S. Niederman. (2004) Antimicrobial therapy of community-acquired pneumonia. Infectious Disease Clinics of North America 18:4, 993-1016
CrossRef102
George G. Zhanel, Heather J. Smith. 2004. Fluoroquinolone Resistance‐Associated Gene Mutations in Streptococcus pneumoniae. , 496-499.
CrossRef103
James S. Tan. (2004) Nonresponses and treatment failures with conventional empiric regimens in patients with community-acquired pneumonia. Infectious Disease Clinics of North America 18:4, 883-897
CrossRef104
P. G. Ambrose, D. Bast, G. V. Doern, P. B. Iannini, R. N. Jones, K. P. Klugman, D. E. Low. (2004) Fluoroquinolone-Resistant Streptococcus pneumoniae, an Emerging but Unrecognized Public Health Concern: Is it Time to Resight the Goalposts?. Clinical Infectious Diseases 39:10, 1554-1556
CrossRef105
Ronald J DeBellis. (2004) Antibiotic-resistant pathogens—epidemiology and clinical relevance. Current Opinion in Pulmonary Medicine 10, S14-S18
CrossRef106
K.P. Klugman, D.E. Low, J Metlay, J.-C. Pechere, K. Weiss. (2004) Community-acquired pneumonia: new management strategies for evolving pathogens and antimicrobial susceptibilities. International Journal of Antimicrobial Agents 24:5, 411-422
CrossRef107
Karen M Speirs, Marcus J Zervos. (2004) Telithromycin. Expert Review of Anti-infective Therapy 2:5, 685-693
CrossRef108
Sanjay Sethi, Thomas M. File. (2004) Managing patients with recurrent acute exacerbations of chronic bronchitis: a common clinical problem. Current Medical Research and Opinion 20:10, 1511-1521
CrossRef109
C.E. Nord, D.J. Farrell, R. Leclercq. (2004) Impact of Ketolides on Resistance Selection and Ecologic Effects during Treatment for Respiratory Tract Infections. Microbial Drug Resistance 10:3, 255-263
CrossRef110
T. M. File. (2004) Clinical Efficacy of Newer Agents in Short-Duration Therapy for Community-Acquired Pneumonia. Clinical Infectious Diseases 39:Supplement 3, S159-S164
CrossRef111
Keith S Kaye, John J Engemann, Henry S Fraimow, Elias Abrutyn. (2004) Pathogens resistant to antimicrobial agents: Epidemiology, molecular mechanisms, and clinical management. Infectious Disease Clinics of North America 18:3, 467-511
CrossRef112
A. W. Karchmer. (2004) Increased Antibiotic Resistance in Respiratory Tract Pathogens: PROTEKT US--An Update. Clinical Infectious Diseases 39:Supplement 3, S142-S150
CrossRef113
R. E. Polk, C. K. Johnson, D. McClish, R. P. Wenzel, M. B. Edmond. (2004) Predicting Hospital Rates of Fluoroquinolone-Resistant Pseudomonas aeruginosa from Fluoroquinolone Use in US Hospitals and Their Surrounding Communities. Clinical Infectious Diseases 39:4, 497-503
CrossRef114
Kazufumi Hiramatsu, Minoru Ohama, Yoshiko Mijajima, Kenji Kishi, Syunji Mizunoe, Issei Tokimatsu, Hiroyuki Nagai, Jun-ichi Kadota, Tetsunori Saikawa, Masaru Nasu. (2004) Antimicrobial susceptibilities and analysis of genes related to penicillin or macrolide resistance in Streptococcus pneumoniae. International Journal of Antimicrobial Agents 24:2, 125-129
CrossRef115
S Sethi, C Fogarty, A Fulambarker. (2004) A randomized, double-blind study comparing 5 days oral gemifloxacin with 7 days oral levofloxacin in patients with acute exacerbation of chronic bronchitis. Respiratory Medicine 98:8, 697-707
CrossRef116
Laura M Koeth, Caryn E Good, Kay A Saunders, Charles Jakielaszek. (2004) Streptococcus pneumoniae in vitro development of resistance to amoxicillin/clavulanic acid, cefaclor, levofloxacin and azithromycin. International Journal of Antimicrobial Agents 24:2, 144-149
CrossRef117
P.C Appelbaum, S.H Gillespie, C.J Burley, G.S Tillotson. (2004) Antimicrobial selection for community-acquired lower respiratory tract infections in the 21st century: a review of gemifloxacin. International Journal of Antimicrobial Agents 23:6, 533-546
CrossRef118
J.-H. Song, S.-I. Jung, H. K. Ki, M.-H. Shin, K. S. Ko, J. S. Son, H.-H. Chang, S. W. Kim, H. Lee, Y.-S. Kim, W. S. Oh, K. R. Peck, A. Chongthaleong, M. K. Lalitha, J. Perera, T. T. Yee, F. Jamal, A. Kamarulzaman, C. C. Carlos, T. So, . (2004) Clinical Outcomes of Pneumococcal Pneumonia Caused by Antibiotic-Resistant Strains in Asian Countries: A Study by the Asian Network for Surveillance of Resistant Pathogens. Clinical Infectious Diseases 38:11, 1570-1578
CrossRef119
I. A. Critchley, J. A. Karlowsky. (2004) Optimal use of antibiotic resistance surveillance systems. Clinical Microbiology and Infection 10:6, 502-511
CrossRef120
D. E. Low. (2004) Quinolone Resistance among Pneumococci: Therapeutic and Diagnostic Implications. Clinical Infectious Diseases 38:Supplement 4, S357-S362
CrossRef121
Ron Dagan, Adriano Arguedas, Urs B. Schaad. (2004) Potential Role of Fluoroquinolone Therapy in Childhood Otitis Media. The Pediatric Infectious Disease Journal 23:5, 390-398
CrossRef122
M. R. Jacobs. (2004) Building in efficacy: developing solutions to combat drug-resistant S. pneumoniae. Clinical Microbiology and Infection 10:s2, 18-27
CrossRef123
Karl Drlica, Xilin Zhao. (2004) Is ‘dosing-to-cure’ appropriate in the face of antimicrobial resistance?. Reviews in Medical Microbiology 15:2, 73-80
CrossRef124
Javier Aspa, Olga Rajas, Felipe Rodriguez de Castro, Jose Blanquer, Rafael Zalacain, Asuncion Fenoll, Rosa de Celis, Antonio Vargas, Francisco Rodriguez Salvanes, Pedro Pablo Espana, Jordi Rello, Antoni Torres, . (2004) Drug‐Resistant Pneumococcal Pneumonia: Clinical Relevance and Related Factors. Clinical Infectious Diseases 38:6, 787-798
CrossRef125
Jorg J. Ruhe, Leann Myers, David Mushatt, Rodrigo Hasbun. (2004) High‐Level Penicillin‐Nonsusceptible Streptococcus pneumoniae Bacteremia: Identification of a Low‐Risk Subgroup. Clinical Infectious Diseases 38:4, 508-514
CrossRef126
Thomas M. File, Jr.. (2004) Current Challenges in the Treatment of Community‐Acquired Pneumonia. Clinical Infectious Diseases 38:S1, S1-S4
CrossRef127
J. B. Kahn, N. Bahal, B. A. Wiesinger, J. Xiang. (2004) Cumulative Clinical Trial Experience with Levofloxacin for Patients with Community‐Acquired Pneumonia–Associated Pneumococcal Bacteremia. Clinical Infectious Diseases 38:S1, S34-S42
CrossRef128
Anna Maria Ferrara, Anna Maria Fietta. (2004) New Developments in Antibacterial Choice for Lower Respiratory Tract Infections in Elderly Patients. Drugs & Aging 21:3, 167-186
CrossRef129
Ronald J DeBellis. (2004) The Role of Resistance and Impact on Appropriate Antimicrobial Use. American Journal of Therapeutics 11, S1-S8
CrossRef130
Sridhar Neralla, Keith C Meyer. (2004) Drug Treatment of Pneumococcal Pneumonia in the Elderly. Drugs & Aging 21:13, 851-864
CrossRef131
JAY M. LIEBERMAN. (2003) Appropriate antibiotic use and why it is important: the challenges of bacterial resistance. The Pediatric Infectious Disease Journal 22:12, 1143-1151
CrossRef132
Thomas M File. (2003) Community-acquired pneumonia. The Lancet 362:9400, 1991-2001
CrossRef133
Öznur Ak, Nur Benzonana, Serdar Özer, Haluk Eraksoy. (2003) Emergence of high-level fluoroquinolone-resistant Streptococcus pneumoniae in Turkey. International Journal of Infectious Diseases 7:4, 288-289
CrossRef134
L. A. Mandell, J. G. Bartlett, S. F. Dowell, T. M. File, D. M. Musher, C. Whitney. (2003) Update of Practice Guidelines for the Management of Community-Acquired Pneumonia in Immunocompetent Adults. Clinical Infectious Diseases 37:11, 1405-1433
CrossRef135
Anne von Gottberg, Herbert Ludewick, Sheila Bamber, Chetna Govind, A. Willem Sturm, Keith P. Klugman. (2003) Emergence of fluoroquinolone-resistant Streptococcus pneumoniae in a South African child in a tuberculosis treatment facility. The Pediatric Infectious Disease Journal 22:11, 1020-1021
CrossRef136
Benjamin A. Kupronis, Chesley L. Richards, Cynthia G. Whitney, . (2003) Invasive Pneumococcal Disease in Older Adults Residing in Long-Term Care Facilities and in the Community. Journal of the American Geriatrics Society 51:11, 1520-1525
CrossRef137
D. R. Murdoch. (2003) Treating legionnaires' disease. Internal Medicine Journal 33:11, 479-481
CrossRef138
Ken Waites, Steve Brown. (2003) Antimicrobial Resistance among Isolates of Respiratory Tract Infection Pathogens from the Southern United States: Data from the PROTEKT US Surveillance Program 2000/2001. Southern Medical Journal 96:10, 974-985
CrossRef139
A. Domenech, C. Cabellos, S. Ribes, F. Tubau, P.F. Viladrich, J. Liñares, F. Gudiol. (2003) Experimental Study of Clinafloxacin Alone and in Combination in the Treatment of Ciprofloxacin-Susceptible and -Resistant Pneumococcal Meningitis. Microbial Drug Resistance 9:supplement 1, 53-59
CrossRef140
Roman Pallares, Asuncion Fenoll, Josefina Liñares. (2003) The epidemiology of antibiotic resistance in Streptococcus pneumoniae and the clinical relevance of resistance to cephalosporins, macrolides and quinolones. International Journal of Antimicrobial Agents 22, 15-24
CrossRef141
John G. Gums. (2003) NCCLS perspectives in changing susceptibility breakpoints for antimicrobial drugs. International Journal of Antimicrobial Agents 22, 3-13
CrossRef142
Dominique Gendrel, Martin Chalumeau, Florence Moulin, Josette Raymond. (2003) Fluoroquinolones in paediatrics: a risk for the patient or for the community?. The Lancet Infectious Diseases 3:9, 537-546
CrossRef143
Douglas N Fish. (2003) Levofloxacin: update and perspectives on one of the original ‘respiratory quinolones’. Expert Review of Anti-infective Therapy 1:3, 371-387
CrossRef144
K. B. Anderson, J. S. Tan, T. M. File, J. R. DiPersio, B. M. Willey, D. E. Low. (2003) Emergence of Levofloxacin-Resistant Pneumococci in Immunocompromised Adults after Therapy for Community-Acquired Pneumonia. Clinical Infectious Diseases 37:3, 376-381
CrossRef145
S. M. Bhavnani, J. P. Hammel, A. Forrest, R. N. Jones, P. G. Ambrose. (2003) Relationships between Patient- and Institution-Specific Variables and Decreased Antimicrobial Susceptibility of Gram-Negative Pathogens. Clinical Infectious Diseases 37:3, 344-350
CrossRef146
MICHAEL R. JACOBS. (2003) Worldwide trends in antimicrobial resistance among common respiratory tract pathogens in children. The Pediatric Infectious Disease Journal 22:Supplement, S109-S119
CrossRef147
V. L. Yu, C. C. C. Chiou, C. Feldman, A. Ortqvist, J. Rello, A. J. Morris, L. M. Baddour, C. M. Luna, D. R. Snydman, M. Ip, W. C. Ko, M. B. F. Chedid, A. Andremont, K. P. Klugman, . (2003) An International Prospective Study of Pneumococcal Bacteremia: Correlation with In Vitro Resistance, Antibiotics Administered, and Clinical Outcome. Clinical Infectious Diseases 37:2, 230-237
CrossRef148
Francesco Blasi, Paolo Tarsia, Roberto Cosentini, Mario Cazzola, Luigi Allegra. (2003) Therapeutic potential of the new quinolones in the treatment of lower respiratory tract infections. Expert Opinion on Investigational Drugs 12:7, 1165-1177
CrossRef149
C. Carbon, S. Moola, I. Velancsics, B. Leroy, M. Rangaraju, P. Decosta. (2003) Telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated treatment for community-acquired pneumonia. Clinical Microbiology and Infection 9:7, 691-703
CrossRef150
Didier Gruson, Gilles Hilbert, Frederic Vargas, Ruddy Valentino, Nam Bui, Sabine Pereyre, Christianne Bebear, Cecile-Marie Bebear, Georges Gbikpi-Benissan. (2003) Strategy of antibiotic rotation: Long-term effect on incidence and susceptibilities of Gram-negative bacilli responsible for ventilator-associated pneumonia*. Critical Care Medicine 31:7, 1908-1914
CrossRef151
Lindsay E. Nicolle. (2003) Empirical treatment of acute cystitis in women. International Journal of Antimicrobial Agents 22:1, 1-6
CrossRef152
Karl Drlica, Xilin Zhao. (2003) Fluoroquinolone-resistant Streptococcus pneumoniae. Reviews in Medical Microbiology 14:3, 95-103
CrossRef153
Jorg J. Ruhe, Rodrigo Hasbun. (2003) Streptococcus pneumoniae Bacteremia: Duration of Previous Antibiotic Use and Association with Penicillin Resistance. Clinical Infectious Diseases 36:9, 1132-1138
CrossRef154
Jan Jelrik Oosterheert, Marc J. M. Bonten, Eelko Hak, Margriet M. E. Schneider, Andy I. M. Hoepelman. (2003) Severe community-acquired pneumonia: whatʼs in a name?. Current Opinion in Infectious Diseases 16:2, 153-159
CrossRef155
Keith P. Klugman. (2003) The Role of Clonality in the Global Spread of Fluoroquinolone‐Resistant Bacteria. Clinical Infectious Diseases 36:6, 783-785
CrossRef156
Javier Garau. (2003) Why do we need to eradicate pathogens in respiratory tract infections?. International Journal of Infectious Diseases 7, S5-S12
CrossRef157
David M Rothstein, Arthur D Hartman, Michael H Cynamon, Barry I Eisenstein. (2003) Development potential of rifalazil. Expert Opinion on Investigational Drugs 12:2, 255-271
CrossRef158
Sandra S. Richter, Daniel J. Diekema, Kris P. Heilmann, Laurel S. Almer, Virginia D. Shortridge, Rod Zeitler, Robert K. Flamm, Gary V. Doern. (2003) Fluoroquinolone Resistance in Streptococcus pyogenes. Clinical Infectious Diseases 36:3, 380-383
CrossRef159
Jay C. Butler, Jeffrey L. Lennox, Linda K. McDougal, Joyce A. Sutcliffe, Amelia Tait‐Kamradt, Fred C. Tenover. (2003) Macrolide‐Resistant Pneumococcal Endocarditis and Epidural Abscess that Develop during Erythromycin Therapy. Clinical Infectious Diseases 36:2, e19-e25
CrossRef160
D. E. Low. (2002) The era of antimicrobial resistance-implications for the clinical laboratory. Clinical Microbiology and Infection 8:s3, 9-20
CrossRef161
ZELL A. MCGEE, NINA GREWAL. (2002) Editorial: The CDCʼs STD Treatment Guidelines Need a New Paradigm. Sexually Transmitted Diseases 29:11, 674-677
CrossRef162
Santiago Ewig, Antoni Torres. (2002) Severe community-acquired pneumonia. Current Opinion in Critical Care 8:5, 453-460
CrossRef163
John Goldberg, Robert C. Owens. (2002) Optimizing antimicrobial dosing in the critically ill patient. Current Opinion in Critical Care 8:5, 435-440
CrossRef164
Eric G Sahloff, Sandy J Close, Steven J Martin. (2002) Evaluation and cost assessment of fluoroquinolones in community-acquired respiratory infections. Expert Opinion on Pharmacotherapy 3:9, 1251-1266
CrossRef165
D. Felmingham, C. Feldman, W. Hryniewicz, K. Klugman, S. Kohno, D. E. Low, C. Mendes, A. C. Rodloff. (2002) Surveillance of resistance in bacteria causing community-acquired respiratory tract infections. Clinical Microbiology and Infection 8, 12-42
CrossRef166
Ronald N. Jones, David R. Andes, Lionel A. Mandell, Samantha Gothelf, Anton F. Ehrhardt, Susan C. Nicholson. (2002) Gatifloxacin used for therapy of outpatient community-acquired pneumonia caused by Streptococcus pneumoniae. Diagnostic Microbiology and Infectious Disease 44:1, 93-100
CrossRef167
Lorenzo Pelly. (2002) IV-to-oral switch therapy for community-acquired pneumonia requiring hospitalization: Focus on gatifloxacin. Advances in Therapy 19:5, 229-242
CrossRef168
Ronald N Jones, Lionel A Mandell. (2002) Fluoroquinolones for the treatment of outpatient community-acquired pneumonia. Diagnostic Microbiology and Infectious Disease 44:1, 69-76
CrossRef169
(2002) Resistance to Levofloxacin and Failure of Treatment of Pneumococcal Pneumonia. New England Journal of Medicine 347:1, 65-67
Full Text170
Lisa L Dever, WG Johanson, Kavitha Shashikumar. (2002) Antibiotics in the treatment of acute exacerbations of chronic bronchitis. Expert Opinion on Investigational Drugs 11:7, 911-925
CrossRef171
Antonio Anzueto, Mark Gotfried, Matthew A. Wikler, Rene Russo, Nicholson C. Susan. (2002) Efficacy and tolerability of gatifloxacin in community treatment of acute exacerbations of chronic bronchitis. Clinical Therapeutics 24:6, 906-917
CrossRef172
John Macfarlane. (2002) Severe pneumonia and a second antibiotic. The Lancet 359:9313, 1170-1172
CrossRef173
Swartz, Morton N., . (2002) Attacking the Pneumococcus — A Hundred Years' War. New England Journal of Medicine 346:10, 722-722
Full Text
- Letters
