The perceived need for intravenous antibiotics drives many hospital admissions. In a sense, the decision to administer IV antibiotics instead of oral formulations represents a line in the sand between infections we are worried might kill a patient and ones that won’t.
Explore This IssueACEP Now: Vol 39 – No 01 – January 2020
But for the vast majority of common infections we treat in the emergency department, oral antibiotics should actually be preferred over IV antibiotics when efficacy, safety, efficiency, and cost are taken into account together. My goal is to convince you to correctly choose oral antibiotics more often. I believe this will lead to fewer admissions, fewer hassles, and less suffering for our patients.
Of course, there are various physiological arguments that support oral antibiotics being theoretically as effective as IV antibiotics. But I know that, in order for us to change our behavior, the only thing that matters is whether data on outcomes support us. Here, I will concentrate on the clinically relevant outcome data for various indications and practical aspects comparing IV to oral antibiotics. Once armed with this knowledge, we should feel more comfortable prescribing pills and discharging rather than ordering IVs and admitting.
UTI and Pyelonephritis
Most urinary tract infections (UTIs) can be managed in the outpatient setting. In a Cochrane review of 15 randomized controlled trials (RCTs) comprising 1,743 children and adults with severe UTI, pooled outcomes showed no significant differences between oral and IV antibiotics.1
But what about pyelonephritis? In adults with pyelonephritis and complicated UTI, oral fluoroquinolones have been shown to be noninferior to IV antibiotics.2,3
And kids? Similarly, a Cochrane review of antibiotics for acute pyelonephritis in well-appearing children older than 1 month of age found no significant differences between oral antibiotics for 14 days and IV antibiotic therapy for three days followed by oral antibiotics, as well as no significant differences in persistent bacteriuria at the end of treatment or persistent kidney damage.4 A review in Annals of Emergency Medicine agreed with this assessment.5
Skin and Soft Tissue Infections
In multiple (albeit small) studies, no difference in clinical resolution of cellulitis has been demonstrated between IV and oral antibiotics for simple cellulitis.6-8 One study, a RCT, found no difference in convenience, complications, effectiveness, overall satisfaction, and mean time to cessation of advancement of cellulitis between oral and IV antibiotics.8 A Cochrane review of 25 studies including 2,588 patients comparing oral and IV antibiotics for uncomplicated cellulitis looking at “symptoms rated by participant or medical practitioner or proportion symptom-free” found that IV antibiotics were no better than oral ones. In fact, two of the studies suggested that oral antibiotics were more effective!9
This comports with the Infectious Diseases Society of America recommendation that IV antibiotics for nonpurulent cellulitis be reserved for patients who are immunocompromised or have systemic signs of infection, hemodynamic instability, or altered mental status.10 In fact, adherence to this guideline has recently been shown to reduce treatment failure rates in ED patients.11 In a recent retrospective chart review of 500 patients, independent predictors of oral antibiotic treatment failure (defined as hospitalization, change in class of oral antibiotic, or switch to IV therapy after 48 hours of oral therapy) for nonpurulent and soft tissue infections included tachypnea at triage, the presence of chronic ulcers, history of methicillin-resistant Staphylococcus aureus colonization or infection, previous recent cellulitis (in the past year), chronic kidney disease, and diabetes.12
One reason that IV antibiotics are overused is an incorrect diagnosis of “treatment failure.” All too often, patients with skin and soft tissue infections are deemed to have failed oral antibiotics after fewer than 48 hours of oral antibiotics. They then are needlessly switched to IV antibiotics. There is no evidence to support this practice. Treatment failure of simple cellulitis should only be entertained after a 48- to 72-hour trial of oral antibiotics. Even in many of these cases, switching classes of oral antibiotics is sufficient. IV antibiotics are not the automatic answer to “treatment failures.”
One of the most common reasons for hospital admission is pneumonia. Several RCTs studying treatment approaches in both adults and children with community-acquired pneumonia have been performed. In comparing oral to IV antibiotics, and in assessing the efficacy of early switches from IV to oral antibiotics, there are no data to support the notion of an advantage to IV therapies in most cases.13-18 A Cochrane review confirms this.19
Febrile Neutropenia, Osteomyelitis, and Endocarditis
Let’s step it up a bit and consider antibiotic route for cancer patients with febrile neutropenia. Many of us reflexively obtain blood cultures and initiate broad-spectrum antibiotic coverage for these patients without batting an eyelash. And yet again, a Cochrane review of 22 RCTs found that, in patients who were hemodynamically stable without evidence of organ failure or obvious source of infection, oral antibiotics (or an early switch to oral antibiotics) were an acceptable alternative to IV antibiotics.20 Both the mortality rate and treatment failure rate were similar between groups.
How about osteomyelitis? You guessed it—a Cochrane review of five RCTs found no statistically significant difference in remission rates between oral and IV antibiotics for patients with chronic osteomyelitis, and a recent RCT of more than 1,000 patients with bone or joint infection in The New England Journal of Medicine found that the one-year failure rate was similar between patients treated with six weeks of oral antibiotics compared to IV antibiotics of the same duration.21,22
Finally, both an RCT from 1996 and a recent one from 2019 found no advantage of oral over IV antibiotics in patients with endocarditis—the former compared oral directly to IV in IV drug users with endocarditis, while the latter compared patients with left-sided endocarditis in stable condition who had been on IV antibiotics for 10 days either continuing IV antibiotics or switching to oral antibiotics.23,24 All-cause mortality, unplanned cardiac surgery, clinically evident embolism, and relapse of bacteremia were no different between groups.
Surely, all patients confirmed to have bacteremia require at least five days of IV antibiotics! Is nothing sacred? But again, in a recent study of almost 5,000 hospitalized patients with Enterobacteriaceae bacteremia, 30-day mortality was no different between patients who received oral step-down after an appropriate clinical response compared with continued IV antibiotics.25 The authors also found that early transition to oral antibiotics decreased hospital length of stay.
Complications, Efficiency, and Cost
Sometimes patients are admitted to hospital “for IV antibiotics” when they can be safely discharged home on oral antibiotics. The cost savings to the health care system as well as decreased risk of nosocomial infections by avoiding admissions are considerable.26 There are validated decision tools to help us safely discharge such patients on oral antibiotics for a variety of conditions.27,28
Naturally, IV antibiotics are generally more expensive than their oral antibiotic equivalents. However, it isn’t only the direct cost of the drugs that needs to be taken into account, but also the indirect costs of using IV antibiotics compared to oral antibiotics. A United Kingdom study looking at nondrug costs of IV antibiotic therapy for patients admitted to hospital with pneumonia or intra-abdominal infections showed that preparation and administration of antibiotics was more time-consuming in those receiving IV antibiotics compared to those receiving oral antibiotics. Use of IV antibiotics was associated with significantly higher workload and additional costs that sometimes were more than the cost of the medications themselves.29 In the ED, it takes longer to administer IV antibiotics than oral ones. Additionally, there are complications of IV antibiotics to consider, including extravasation injury, phlebitis, as well as local or systemic infection.30 The risk of bacteraemia caused by a peripheral IV can be as high as 0.1%.26 Even antibiotic-associated diarrhea and secondary infections with Clostridium difficile have been shown to be more prevalent in ED patients given a single dose of IV antibiotics before being discharged on oral antibiotics compared to oral antibiotics alone.31
Taken together, these data support the argument that if we used oral antibiotics for most common infections in the ED, we could safely improve throughput and efficiency and decrease our patients’ suffering. So, next time you are faced with a stable non-critically ill patient with a UTI, cellulitis, pneumonia, osteomyelitis, or febrile neutropenia (who is not vomiting and has low aspiration risk), ask yourself whether IV antibiotics are necessary.
If we all chose oral antibiotics most of the time in these situations, we could improve ED efficiency and overcrowding, prevent complications associated with IV insertion, and save our health care system money while safely and effectively providing excellent care for our patients. Meet with your ED group to integrate oral antibiotics choices into your electronic medical records. That alone is likely to help nudge us and our colleagues in the right direction.
Thanks to Dr. Andrew Morris for his contributions to the EM Cases podcasts that inspired this article.
- Pohl A. Modes of administration of antibiotics for symptomatic severe urinary tract infections. Cochrane Database Syst Rev. 2007;(4):CD003237.
- Mombelli G, Pezzoli R, Pinoja-Lutz G, et al. Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial. Arch Intern Med. 1999;159(1):53-58.
- Lojanapiwat B, Nimitvilai S, Bamroongya M, et al. Oral sitafloxacin vs intravenous ceftriaxone followed by oral cefdinir for acute pyelonephritis and complicated urinary tract infection: a randomized controlled trial. Infect Drug Resist. 2019;12:173-181.
- Strohmeier Y, Hodson EM, Willis NS, et al. Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev. 2014;(7):CD003772.
- Cruz C, Spina L. Are oral antibiotics as effective as a combination of intravenous and oral antibiotics for kidney infections in children? Ann Emerg Med. 2016;67(1):30-31.
- Bernard P, Chosidow O, Vaillant L. Oral pristinamycin versus standard penicillin regimen to treat erysipelas in adults: randomised, non-inferiority, open trial. BMJ. (Clinical research ed.). 2002;325(7369):864.
- Jorup-Rönström C, Britton S, Gavlevik A, et al. The course, costs and complications of oral versus intravenous penicillin therapy of erysipelas. Infection. 1984;12(6):390-394.
- Aboltins CA, Hutchinson AF, Sinnappu RN, et al. Oral versus parenteral antimicrobials for the treatment of cellulitis: a randomized non-inferiority trial. J Antimicrob Chemother. 2015;70(2):581-586.
- Kilburn SA, Featherstone P, Higgins B, et al. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev. 2010;(6):CD004299.
- Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52.
- Haran JP, Wilsterman E, Zeoli T, et al. Deviating from IDSA treatment guidelines for non-purulent skin infections increases the risk of treatment failure in emergency department patients. Epidemiol Infect. 2018;147:e68.
- Yadav K, Suh KN, Eagles D, et al. Predictors of oral antibiotic treatment failure for nonpurulent skin and soft tissue infections in the emergency department. Acad Emerg Med. 2019;26(1):51-59.
- Oosterheert JJ, Bonten MJ, Schneider MM, et al. Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial. BMJ. 2006;333(7580):1193.
- Siegel RE, Halpern NA, Almenoff PL, et al. A prospective randomized study of inpatient iv. antibiotics for community-acquired pneumonia. The optimal duration of therapy. Chest. 1996;110(4):965-971.
- Atkinson M, Lakhanpaul M, Smyth A, et al. Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial. Thorax. 2007;62(12):1102-1106.
- Addo-Yobo E, Chisaka N, Hassan M, et al. Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study. Lancet. 2004;364(9440):1141-1148.
- Agweyu A, Gathara D, Oliwa J, et al. Oral amoxicillin versus benzyl penicillin for severe pneumonia among Kenyan children: a pragmatic randomized controlled noninferiority trial. Clin Infect Dis. 2015;60(8):1216-1224.
- Castro-Guardiola A, Viejo-Rodríguez AL, Soler-Simon S, et al. Efficacy and safety of oral and early-switch therapy for community-acquired pneumonia: a randomized controlled trial. Am J Med. 2001;111(5):367-374.
- Pakhale S, Mulpuru S, Verheij TJ, et al. Antibiotics for community‐acquired pneumonia in adult outpatients. Cochrane Database Syst Rev. 2014;(10):CD002109.
- Vidal L, Ben Dor I, Paul M, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst Rev. 2013;(10):CD003992.
- Conterno LO, Turchi MD. Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev. 2013;(9):CD004439.
- Li HK, Rombach I, Zambellas R, et al. Oral versus intravenous antibiotics for bone and joint infection. N Engl J Med. 2019;380(5):425-436.
- Heldman AW, Hartert TV, Ray SC, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med. 1996;101(1):68-76.
- Iversen K, Ihlemann N, Gill SU, et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N Engl J Med. 2019;380(5):415-424.
- Tamma PD, Conley AT, Cosgrove SE, et al. Association of 30-day mortality with oral step-down vs continued intravenous therapy in patients hospitalized with Enterobacteriaceae bacteremia. JAMA Intern Med. 2019;179(3):316-323.
- Maki DG, Kluger DM, Crnich CJ. The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc. 2006;81(9):1159-1171.
- Marras TK, Gutierrez C, Chan CK. Applying a prediction rule to identify low-risk patients with community-acquired pneumonia. Chest. 2000;118(5):1339-1343.
- Klastersky J, Paesmans M, Georgala A, et al. Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. J Clin Oncol. 2006;24(25):4129-4134.
- van Zanten AR, Engelfriet PM, van Dillen K, et al. Importance of nondrug costs of intravenous antibiotic therapy. Crit Care. 2003;7(6):R184-190.
- Li HK, Agweyu A, English M, et al. An unsupported preference for intravenous antibiotics. PLoS Medicine. 2015;12(5):e1001825.
- Haran JP, Hayward G, Skinner S, et al. Factors influencing the development of antibiotic associated diarrhea in ED patients discharged home: risk of administering IV antibiotics. Am J Emerg Med. 2014; 32(10):1195-1199.