Keeping it Short and Sweet: New Antibiotic Treatment Duration Recommendations

by Kaitlin Cauthen, PharmD Candidate and Jamie Wagner, PharmD, BCPS

Antibiotics are one of the greatest advancements in medicine; however, antibiotic resistance is a significant worldwide public health challenge due, in part, to overuse and misuse.^1,2,3 This adversely affects both individual patients and healthcare systems. For the patient, antibiotic overuse leads to undesirable effects like gastrointestinal distress, allergic reactions, or Clostridioides difficile infections.⁴ For the healthcare system, antibiotic resistance leads to higher treatment costs and longer hospital stays.² Antibiotic stewardship programs (ASPs) have emerged to thwart the development of resistant bacteria and ensure antibiotics remain effective when needed. The primary focus of ASPs is to optimize antibiotic therapy by selecting the “right” drug for an appropriate duration.⁵ Unfortunately, many clinicians avoid short course therapy despite compelling evidence that short-course regimens can achieve similar outcomes as longer course regimens.⁶

In April 2021, the American College of Physicians developed best practice advice (BPA) for internists, family physicians, and other prescribers to encourage shorter treatment durations for four common outpatient infections: symptomatic adults with acute bronchitis with chronic obstructive pulmonary disease (COPD) exacerbation, community-acquired pneumonia (CAP), urinary tract infections (UTIs), and cellulitis.⁷ There are some caveats to these recommendations. First, while this is a narrative review that combined published guidelines and relevant studies from peer-reviewed literature, the authors of the report did not evaluate the quality of the included guidelines and studies. Second, the recommendations assume that the patient’s diagnosis is correct and the selected antibiotic is appropriate. Should a patient’s condition not improve after the recommended treatment duration, prescribers should reassess the patient to determine other causes instead of increasing the duration of therapy. Lastly, these recommendations do not apply to patients with complicated anatomy.

BPA – Recommendation 1: Clinicians should limit antibiotic treatment duration to 5 days when managing patients with COPD exacerbations and acute uncomplicated bronchitis who have clinical signs of a bacterial infection (presence of increased sputum purulence in addition to increased dyspnea, and/or increased sputum volume).

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend treating moderate to severe exacerbations of COPD with antibiotics.⁸ Typical pathogens that must be covered include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. GOLD recommends treating exacerbations for 5-7 days with an aminopenicillin and clavulanic acid, a macrolide, or a tetracycline. A meta-analysis showed no difference in clinical improvement between groups of patients receiving short-courses vs longer courses of treatment (4.9 days vs 8.3 days), and a sub-analysis of the different antibiotic classes also showed no difference between duration groups.⁹ Therefore, the BPA recommends a 5-day duration for treating COPD exacerbations if the patient has clinical signs of bacterial infection.⁷

BPA – Recommendation 2: Clinicians should prescribe antibiotics for community-acquired pneumonia for a minimum of 5 days. Extension of therapy after 5 days of antibiotics should be guided by validated measures of clinical stability, which include resolution of vital sign abnormalities, ability to eat, and normal mentation.

CAP is a respiratory infection characterized by purulent sputum, dyspnea, and pleuritic chest pain.  Common bacterial pathogens for CAP include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella spp., Chlamydia pneumoniae, and Moraxella catarrhalis.¹⁰ Amoxicillin, doxycycline, or a macrolide are the antibiotics of choice for healthy adults, and a beta-lactam in combination with a macrolide or respiratory fluoroquinolone are recommended for patients with comorbidities, such as chronic heart disease or diabetes mellitus.¹⁰ The IDSA/ATS guidelines recommend a minimum treatment duration of 5 days, as well as withdrawing antibiotic treatment 48 hours after reaching clinical stability (~5 days in most cases).¹¹ A recent trial assessed the effectiveness of 3 days of beta-lactam therapy in 706 non-critically ill patients diagnosed with CAP. All patients received 3 days of beta-lactam treatment and then were randomly assigned to receive placebo or additional beta-lactam treatment. This study showed non-inferiority between the two treatment durations.¹²  While more studies are needed, these data suggest that 5-days may be too long in some cases of CAP.

BPA – Recommendation 3: In women with uncomplicated bacterial cystitis, clinicians should prescribe short-course antibiotics with either nitrofurantoin for 5 days, trimethoprim–sulfamethoxazole (TMP–SMZ) for 3 days, or fosfomycin as a single dose. In men and women with uncomplicated pyelonephritis, clinicians should prescribe short-course therapy either with fluoroquinolones (5 to 7 days) or TMP–SMZ (14 days) based on antibiotic susceptibility.

UTIs are most commonly caused by Escherichia coli, and typical symptoms include urinary urgency and frequency for cystitis and flank pain and fever for pyelonephritis.¹³ The duration of treatment varies with what antibiotic is prescribed. The BPA recommendations for cystitis and pyelonephritis are consistent with the IDSA guidelines¹³ and by randomized controlled trials (RCTs) for pyelonephritis.^7,14 The durations recommended in this BPA are not appropriate for complicated cases, which include structural or functional abnormalities of the genitourinary tract, pregnant women, or acute bacterial prostatitis.⁷

BPA – Recommendation 4: In patients with nonpurulent cellulitis, clinicians should use a 5- to 6-day course of antibiotics active against streptococci, particularly for patients able to self-monitor and who have close follow-up with primary care.

Nonpurulent cellulitis is a diffuse, superficial, spreading skin infection caused by Streptococci and sometimes methicillin-resistant S. aureus (MRSA).¹⁵ It is usually treated with a cephalosporin or a penicillin, and, when needed, MRSA coverage with TMP-SMZ, doxycycline, or clindamycin. The current guideline-recommended treatment duration for nonpurulent cellulitis is 5 days, with treatment extending only if symptoms have not improved.¹⁵ Several RCTs have shown similar rates of cure between shorter and longer durations of antibiotic therapy: 5 days vs 10 days (fluoroquinolones), 6 days vs 10 days (oxazolidinones), and 6 days vs 12 days (flucloxacillin).^16–18 However, it is important to note that patients in the 6-day flucloxacillin group had higher 90-day relapse rates.¹⁶ While more studies are needed to determine the most appropriate duration of treatment for nonpurulent cellulitis, a 5- to 6-day course of most antibiotics will be sufficient.

The bottom line:  Short-course antibiotic regimens are appropriate for many common infections seen in ambulatory care settings.  However, clinicians must be diligent in their follow-up to ensure that the patient has responded and to consider alternative diagnoses and treatments if the patient’s symptoms have not improved.

🎙 Listen to the Annals on Call Podcast – The Right Antibiotic, for the Right Infection, and for the Right Duration about the ACP recommendations for short-course therapy with antibiotics for these common infections.

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