Shorter Is Bettter Master Table 5-21_Pag
Shorter Is Bettter Master Table 5-21_Pag
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References for Shorter Is Better Table

Community Acquired Pneumonia: 12 RCTs (total N = 7,295 patients)

  1. Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000; 162(2 Pt 1): 505-11.

  2. Dunbar LM, Khashab MM, Kahn JB, Zadeikis N, Xiang JX, Tennenberg AM. Efficacy of 750-mg, 5-day levofloxacin in the treatment of community-acquired pneumonia caused by atypical pathogens. Current medical research and opinion 2004; 20(4): 555-63.

  3. Zhao X, Wu JF, Xiu QY, et al. A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg intravenous infusion in the treatment of community-acquired pneumonia. Diagn Microbiol Infect Dis 2014; 80(2): 141-7.

  4. Pakistan Multicentre Amoxycillin Short Course Therapy pneumonia study g. Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. Lancet 2002; 360(9336): 835-41.

  5. Greenberg D, Givon-Lavi N, Sadaka Y, Ben-Shimol S, Bar-Ziv J, Dagan R. Short-course antibiotic treatment for community-acquired alveolar pneumonia in ambulatory children: a double-blind, randomized, placebo-controlled trial. The Pediatric infectious disease journal 2014; 33(2): 136-42.

  6. el Moussaoui R, de Borgie CA, van den Broek P, et al. Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study. Bmj 2006; 332(7554): 1355.

  7. Uranga A, Espana PP, Bilbao A, et al. Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial. JAMA internal medicine 2016; 176(9): 1257-65.

  8. Dinh A, Davido B, Bouchand F, Duran C, Ropers J, Cremieux AC. Honey, I shrunk the antibiotic therapy. Clin Infect Dis 2018; 66(12):1981-2.

  9. Harris JA, Kolokathis A, Campbell M, Cassell GH, Hammerschlag MR. Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children. The Pediatric infectious disease journal 1998; 17(10): 865-71.

  10. Ginsburg AS, Mvalo T, Nkwopara E. et al. Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children. NEJM.  2020 383: 13-23.

  11. Pernica JM, Harman S, Kam AJ, et al. Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia. JAMA Pediatrics, 2021; DOI: 10.1001/jamapediatrics.2020.6735.

  12. Dinh A, Ropers J, Duran C, et al.  Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial. Lancet. 2021 397:1195-1203.

Atypical Community Acquired Pneumonia: 1 RCTs (total N = 100 patients)

  1. Schonwald S, Kuzman I, Oresković K, et al. Azithromycin: single 1.5 g dose in the treatment of patients with atypical pneumonia syndrome--a randomized study. Infection 1999; 22(3):198-202.

Nosocomial/Ventilator Associated Pneumonia: 2 RCTs (total N = 626 patients)

  1. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA : the journal of the American Medical Association 2003; 290(19): 2588-98.

  2. Capellier G, Mockly H, Charpentier C, et al. Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment. PLoS One 2012; 7(8): e41290.

Complicated UTI/Pyelonephritis: 9 RCTs (total N = 1,814 patients)

  1. Jernelius H, Zbornik J, Bauer CA. One or three weeks' treatment of acute pyelonephritis? A double-blind comparison, using a fixed combination of pivampicillin plus pivmecillinam. Acta Med Scand 1988; 223(5): 469-77.

  2. de Gier R, Karperien A, Bouter K, et al. A sequential study of intravenous and oral Fleroxacin for 7 or 14 days in the treatment of complicated urinary tract infections. Int J Antimicrob Agents 1995; 6(1): 27-30.

  3. Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial. JAMA : the journal of the American Medical Association 2000; 283(12): 1583-90.

  4. Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet 2012; 380(9840): 484-90.

  5. Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology 2008; 71(1): 17-22.

  6. Klausner HA, Brown P, Peterson J, et al. A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis. Current medical research and opinion 2007; 23(11): 2637-45.

  7. Dinh A, Davido B, Etienne M, et al.  Is 5 days of oral fluoroquinolone enough for acute uncomplicated pyelonephritis? The DTP randomized trial.  Eur J Clin Microbiol Infect Dis.  2017; 36:1443-8.

  8. van Nieuwkoop C, van der Starre WE, Stalenhoef JE, et al.  Treatment duration of febrile urinary tract
    infection: a pragmatic randomized, doubleblind, placebo-controlled non-inferiority trial in men and women.  BMC Medicine.  2017; 15:70-8.

  9. Drekonja DM, Trautner B, Amundson C, et al.  Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial.  JAMA 2021; 326(4):324-331.

Honorable mention: 2 weeks vs. 4 weeks (long vs. really long)--no difference in clinical cure

Ulleryd and Sandberg.  Ciprofloxacin for 2 or 4 weeks in the treatment of febrile UTI in men: a randomizsed trial with a 1 year follow-up.  Scan J Infect Dis.  2003; 35:34-39.  


Complicated Intra-Abdominal Infections: 2 RCTs (total N = 766 patients)

  1. Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med 2015; 372(21): 1996-2005.

  2. Montravers P, Tubach F, Lescot T, et al. Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial. Intensive Care Med 2018; 44(3):300-310.


GNB Bacteremia: 3 RCTs (total N = 1,186 patients; not including multiple cUTI/cIAI pts in above trials who were also bacteremic)

  1. Yahav D, Franceschini E, Koppel F, et al. Seven versus fourteen Days of Antibiotic Therapy for uncomplicated Gram-negative Bacteremia: a Non-inferiority Randomized Controlled Trial. Clin Infect Dis 2019 69:1091-8.

  2. von Dach E, Albrich WC, Brunel AS, et al. Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial. JAMA. 2020. 323:2160-9.

  3. Molina J, Montero-Matos E, Praena-Segovia J, et al. Seven versus 14-days course of antibiotics for the treatment of bloodstream infections by Enterobacterales. A randomized, controlled trial.  Clin Microbiol Infect. 2021.  ePub.

​​Acute Bacterial Skin and Skin Structure Infections: 4 RCTs (3 non-inferior, total N = 1,412 patients; 1 trial, N = 151 of low dose oral fluclox which is poorly absorbed had excess relapses at 90 d)

  1. Hepburn MJ, Dooley DP, Skidmore PJ, Ellis MW, Starnes WF, Hasewinkle WC. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med 2004; 164(15): 1669-74.

  2. Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA : the journal of the American Medical Association 2013; 309(6): 559-69.

  3. Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis 2014; 14(8): 696-705.

  4. Cranendonk et al.  Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomised, double-blind, placebo-controlled, non-inferiority trial.  Clin Microbiol Infect 2019; 26(5):606-612.


Osteomyelitis Not Surgically Treated 6 vs. 12 weeks: 2 RCTs (total N = 391 patients)

  1. Bernard L, Dinh A, Ghout I, et al. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial. Lancet 2015.  385:875-82.

  2. Tone A, et a. Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomized study. Diabetes Care 2015;38:302-307.

Osteomyelitis with Removed Orthopedic Implant: 1 RCT (total N = 123 patients, including 39 pts with 2-stage exchanged PJI)

  1. Benkabouche M, Racloz G, Spechbach H, et al. Four versus six weeks of antibiotic therapy for osteoarticular infections after implant removal: a randomized trial. J Antimicrobial Chemother 2019.  74:2394-2399.

Diabetic Foot Osteomyelitis with Debridement or Total Bone Resection: 2 RCTs (total N = 130 patients)

  1. Lazaro-Martinez J, Aragon-Sanchez J, Garcia-Martinez E, et al. Antibiotics versus conservative surgery for treating diabetic foot osteomyelitis: a randomized comparative trial. Diabetes Care 2014;37:789-95.

  2. Gariani K, Pham T-T, Kressman B, et al. Three versus six weeks of antibiotic therapy for diabetic foot osteomyelitis: A prospective, randomized, non-inferiority pilot trial. Clin Infect Dis 2021.  ePub.


Septic Arthritis: 1 RCTs (total N = 154 patients)

  1. Gjika E, et al. Two weeks versus four weeks of antibiotic therapy after surgical drainage for native joint bacterial arthritis: a prospective, randomised, non-inferiority trial. Ann Rheum Dis 2019; 78:1114–1121.

Acute Exacerbation Chronic Bronchitis/COPD: >20 RCTs (total N = 10,698 patients)

  1. El Moussaoui R, Roede BM, Speelman P, Bresser P, Prins JM, Bossuyt PM. Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies. Thorax 2008; 63(5):415-22.

Acute Bacterial Sinusitis: 6 RCTs (total N = 2,423 patients)

  1. Henry DC, Riffer E, Sokol WN, Chaudry NI, Swanson RN. Randomized double-blind study comparing 3- and 6-day regimens of azithromycin with a 10-day amoxicillin-clavulanate regimen for treatment of acute bacterial sinusitis. Antimicrob Agents Chemother. 2003;47(9):2770-2774.

  2. Ferguson BJ, Anon J, Poole MD, et al. Short treatment durations for acute bacterial rhinosinusitis: Five days of gemifloxacin versus 7 days of gemifloxacin. Otolaryngol Head Neck Surg. 2002;127(1):1-6.

  3. Sher LD, McAdoo MA, Bettis RB, Turner MA, Li NF, Pierce PF. A multicenter, randomized, investigator-blinded study of 5- and 10-day gatifloxacin versus 10-day amoxicillin/clavulanate in patients with acute bacterial sinusitis. Clin Ther. 2002;24(2):269-281.

  4. Roos K, Brunswig-Pitschner C, Kostrica R, et al. Efficacy and tolerability of once-daily therapy with telithromycin for 5 or 10 days for the treatment of acute maxillary sinusitis. Chemotherapy. 2002;48(2):100-108.

  5. Williams JW Jr, Holleman DR Jr, Samsa GP, Simel DL. Randomized controlled trial of 3 vs 10 days of trimethoprim/sulfamethoxazole for acute maxillary sinusitis. JAMA. 1995;273(13):1015-1021.

  6. Klapan I, Culig J, Oresković K, Matrapazovski M, Radosević S. Azithromycin versus amoxicillin/clavulanate in the treatment of acute sinusitis. Am J Otolaryngol. 1999;20(1):7-11.

 (special thanks to Dr. Fernando Dominguez @FDominguezID for identifying the ABS trials!)​

Neutropenic Fever: 1 RCTs (total N = 157 patients)

  1. Aguilar-Guisado M, Espigado I, Martin-Pena A, et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol 2017; 4(12): e573-e83.


P. vivax Malaria: 1 RCTs (total N = 1,872 patients)

  1. Taylor W, et al. Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial. Lancet 2019; 394(10202):929-938.

References for Shorter Is Better: TB Is Complex

Latent TB: 8 RCTs (total N = 21,140 patients)

  1. Sterling TR, Scott NA, Miro JM, et al. Tuberculosis Trials Consortium, the AIDS Clinical Trials Group for the PREVENT TB Trial (TBTC Study 26ACTG 5259).  Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons. AIDS 2016;30:1607–15.

  2. Martinson NA, Barnes GL, Moulton LH, et al. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med 2011;365:11–20.

  3. Sterling TR, Villarino ME, Borisov AS, et al. TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 2011;365:2155–66.

  4. Villarino ME, Scott NA, Weis SE, et al. International Maternal Pediatric and Adolescents AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr 2015;169:247–55.

  5. Diallo T, Adjobimey M, Ruslami R, et al. Safety and side e􀃗ffects of rifampin versus isoniazid in children. N Engl J Med 2018;379:454–63.

  6. Menzies D, Adjobimey M, Ruslami R, et al. Four months of rifampin or nine months of isoniazid for latent tuberculosis in adults. N Engl J Med 2018;379:440–53.

  7. Menzies D, Dion MJ, Rabinovitch B, Mannix S, Brassard P, Schwartzman K. Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid for 9 months. Am J Respir Crit Care Med 2004;170:445–9.

  8. Swindells , Ramchandani R, Gupta A, et al.  One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. New Eng J Med. 2019;380:1001-1011.

Active Pulmonary Tuberculosis: 6 mo vs. 18 mo: 1 RCT (total N = 860 patients)

Controlled clinical trial of four short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Second report. Lancet. 1973; 1(7816):1331-8.

Active Pulmonary Tuberculosis: 4 mo RIPE vs. 6 mo: 1 RCT (total N = 330 patients)

Long-term follow-up of a clinical trial of six-month and four-month regimens of chemotherapy in the treatment of pulmonary tuberculosis. Singapore Tuberculosis Service/British Medical Research Council. Am Rev Respir Dis. 1986; 133:779-83.

Active Pulmonary Tuberculosis: 4 mo Rifapentine-Moxi-INH vs. 6 mo RIPE: 1 RCT (total N = 2343 patients)

Dorman SE, Nahid P, Kurbatova EV, et al. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. New Eng J Medicine. 2021; 384:1705-1718.--Study demonstrated statistical non-inferiority of rifapentine + INH + moxifloxacin (but not rifapentine + INH), but with a trend in the wrong direction, including for the Per Protocol population more failures (+3% (95% CI +1-5%)).

Active Abdominal Tuberculosis: 6 mo vs. 12 mo: 1 RCT (total N = 193 patients)

Balasubramanian R, Nagarajan M, Balambal R, et al. Randomised controlled clinical trial of short course chemotherapy in abdominal tuberculosis: a five-year report. Int J Tuberc Lung Dis. 1997; 1:44-51.

Active Lymph Node Tuberculosis: 6-9 mo vs. 18 mo: 2 RCT (total N = 351 patients)

1. Short course chemotherapy for tuberculosis of lymph nodes: a controlled trial. British Thoracic Society Research Committee. Brit Med J. 1985; 290:1106-8.

2. Campbell IA, Ormerod LP, Friend JA, et al.  Six months versus nine months chemotherapy for tuberculosis of lymph nodes: final results. British Thoracic Society Research Committee. Respir Med. 1993; 87:621-3. 

Active Spinal Tuberculosis: 6 mo vs. 9 mo vs. 18 mo: 1 RCT (total N = 436 patients)

Five-year assessment of controlled trials of short-course chemotherapy regimens of 6, 9 or 18 months' duration for spinal tuberculosis in patients ambulatory from the start or undergoing radical surgery. Fourteenth report of the Medical Research Council Working Party on Tuberculosis of the Spine. Int Orthop. 1999; 23:73-81.

References for Shorter Is Better Exceptions

Prosthetic Joint Infections:

Combined DAIR, 1-, and 2-Stage Exchanges 

1 RCT (total N = 410 patients)

Bernard L, Arvieux C, Brunschweiler B, et al. Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection. New Eng J Medicine 2021; ePub.--6 weeks clearly inferior overall, and particularly for hte DAIR cohort

DAIR Only: Early Infection Onset (< 1 month After Implant) 

1 RCT (total N = 63 patients)

Lora-Tamayo J, Euba G, Cobo J, et al. Short- versus long-duration levofloxacin plus rifampicin for acute staphylococcal prosthetic joint infection managed with implant retention: a randomised clinical trial. Int J Antimicrob Agents 2016;48:310-6.

Otitis Media < 2 Years Old: 1 RCT (total N = 520 patients)

Hoberman A, Paradise JL, Rockette HE, et al. Shortened Antimicrobial Therapy for Otitis Media in Young Children. New Eng J Medicine. 2016; 375:2446-2456.

Otitis Media > 2 Years Old: Meta-Analysis of 49 Trials

Kozyrskyj A, Klassen TP, Moffatt M, and Harvey K. Short-course antibiotics for acute otitis media. Cochrane Database Syst Rev 2010 Issue 9 Pages CD001095.

Strep Throat:

See systematic review: Holm AE, Carl Llor LB, Cordoba G.  Short- vs. Long-Course Antibiotic Treatment for Acute Streptococcal Pharyngitis: Systematic Review and Meta-Analysis of Randomized Controlled Trials.  Antibiotics.  2020;9:733.  Summarizing 5 RCTs of PCN 3-5 d vs. 7-10 d showing shorter course resulted in more short term clinical failures; and summarizing >20 RCTs of 3-5 d of numerous other antibiotics (cephalosporins, macrolides, clindamycin)  vs. 10 d PCN generally showing similar outcomes of shot vs. long therapy.

1 recent RCT: Stahlgren GS, Tyrstrup M, Edlund C, et al.  Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study.  BMJ.  2019;367:l5337., showing similar cure rate of the shorter course, more frequent regimen, with fewer new episodes of tonsillitis and fewer adverse events in the short course arm, but a small decrease in eradication of colonization (80% vs. 90%).