Your response to Stacey can explain that antibiotics will not help her feel better. Antibiotics are not indicated, nor expected to be of benefit for influenza. Influenza is caused by a virus and antibiotics cannot cure a virus. It would be appropriate to discuss with her that the natural history of influenza infection, or what we normally expect in the case of flu, would suggest that her symptoms are likely to improve within 5-7 days. You can also give her clear information about when antibiotics would be beneficial. You can advise that she should return if she develops symptoms that point towards a secondary bacterial infection, such as persistent fever, increasing difficulty breathing, or if her symptoms do not improve over the next 3-4 days.

A key component in this case is effectively communicating with the patient to ensure they understand the reasoning behind not prescribing antibiotics. Often, providing a written handout can ensure that your patient retains the key messages you have discussed and may help them feel they have ‘gotten something’ out of the appointment. One such resource is the Viral Prescription Pad (see References). This resource helps patients understand their diagnosis, gives recommended over-the-counter analgesics they can use, and instructions to return if certain symptoms arise.

This would also be an ideal time to discuss the benefits of the annual influenza vaccination and health promotion strategies for the future. You can remind Stacey that building good hand washing habits is a simple and effective way to prevent the flu.  

Sometimes good antimicrobial stewardship practice involves knowing when medications other than antibacterial agents are likely to be of benefit. It is important to note, although not applicable in this case, that there are certain factors that put patients with influenza virus infection at a higher risk for progressive disease. These include severe disease (requiring hospitalization); however, some patients with milder disease are at risk for severe disease (see Risk Factors). In these patients with suspected or proven influenza, antiviral medication (oseltamivir) would be indicated if they presented to clinic within 48 hours of symptom onset to reduce the risk of severe outcomes such as hospitalization or death. 

BEST ANSWER: 4. No treatment necessary

Teaching Points:

Asymptomatic bacteriuria (ASB) is the presence of one or more species of bacteria growing in the urine (≥10^5 colony-forming units [CFU]/mL or ≥10^8 CFU/L), regardless of the presence of pyuria, in the absence of signs or symptoms attributable to urinary tract infection (UTI). The patient described here does not have any signs or symptoms that are associated with UTIs, which include dysuria and urinary frequency, (see UTI Symptoms). Cloudy or foul-smelling urine are not indicative of a urinary tract infection in the absence of symptoms.

A positive urine leucocyte esterase test reliably identifies pyuria but may be seen in other inflammatory disorders of the pelvis or genitourinary tract. A nitrite test is also of limited value because urinary tract infections can still occur with non-nitrite producing uropathogens. False positives can also be seen with delays in sample testing. Although the combination of a positive leucocyte esterase and a positive nitrite is more specific to bacteriuria, these tests do not distinguish between those patients with asymptomatic bacteriuria and those that are symptomatic (i.e. have a UTI). 

To summarize, a urinalysis that is negative for both nitrites and pyuria does indicate that a UTI is unlikely, but even a positive urinalysis for both nitrites and pyuria in absence of symptoms (see Box) does not ‘rule in’ a UTI, and could indicate ASB.

ASB should not be treated. Exceptions to this rule include treatment of ASB in pregnant women and prior to an invasive urological procedure where bleeding can occur. Further, changes to urine such as foul-smelling or cloudy urine, in the absence of symptoms of a UTI, should not prompt testing. A urine culture in an asymptomatic patient (excluding those with indications listed above) is unnecessary and can lead to wasted healthcare resources, as well as unnecessary antibiotic prescriptions. Antibiotic therapy exposes patients to risk of adverse effects and promotes antibiotic resistance. Caution against unnecessary treatment should be taken, especially for older adults living in long-term care homes where the prevalence of ASB can be up to 50%. 

BEST ANSWER: 3. Treat with amoxicillin for 5 days

Teaching Points:

Based on guidelines, asymptomatic bacteriuria (ASB) is defined as >10^8 CFU/L of uropathogens identified on urine culture, which is still present on repeat urine culture testing. Repeat testing will help to exclude the possibility that your patient is among the ~20% of individuals who will spontaneously clear the ASB. Practically speaking, however, a repeat urine culture is rarely pursued in clinical practice.

In most patients, asymptomatic bacteriuria should not be treated, but in pregnant women, screening for ASB during the first trimester, or on their first obstetrical visit, is indicated. If the screening urine culture is positive, treatment is indicated to reduce the risk of pyelonephritis and spontaneous abortion. Pregnant individuals are tested routinely during pregnancy and, if urine cultures are positive for uropathogens, are treated.

Beta-lactam antibiotics such as amoxicillin or cephalexin are the safest choices of antibiotics to give to someone during pregnancy. Nitrofurantoin is also a safe choice in pregnancy, except in patients at term (i.e. 38-42 weeks), due to the risk of hemolytic anemia in the newborn.  However, nitrofurantoin is noted to be resistant in this case. Trimethoprim-sulfamethoxazole is contraindicated in the first trimester due to its action as a folate antagonist causing neural tube defects. Also, fluoroquinolones are generally not recommended during pregnancy due to potential fetal bone toxicity.

BEST ANSWER: A. No treatment necessary

1. No treatment is necessary.
2. Vancomycin 125 mg PO QID for 10 – 14 days
3. Vancomycin 125 mg PO QID for 10 – 14 days; followed by a ‘taper and pulse’ extended regimen of vancomycin (e.g., 125 mg PO TID for 7 days, 125 mg PO BID for 7 days, 125 mg PO once daily for 7 days, and then every 3 days for 2 – 3 weeks)
4. Fidoxamicin 100 mg PO BID for 10 days
5. Metronidazole 500 mg PO TID for 10 – 14 days

Teaching Points: Clostridioides difficile is a common cause of antibiotic-associated colitis. Transmitted via the fecal-oral route, colonization of the intestinal tract with C. difficile also occurs in 3-5% of healthy adults. Risk factors for disease due to C. difficile (termed C. difficile infection, CDI) include antibiotic use, which is the most common and modifiable factor, as well as older age, hospitalization, and chronic comorbid illness.

Diagnosis of C. difficile infection is based on the presence of clinical symptoms (unexplained, new onset diarrhea of ≥ 3 unformed stools in 24 hours) along with a diagnostic test that detects C. difficile organism or toxin production. In Manitoba, C. difficile testing is performed using a 2-stage approach, initially with GDH antigen screen (very sensitive, poor specificity) followed by testing for C. difficile toxin A & B via nucleic acid amplification testing (NAAT). It is important to recognize that, in some cases, both recent treatment of C. difficile, as well as asymptomatic carriage of C. difficile can lead to false positive results. This can lead to over treatment. For this reason, in accredited clinical microbiology laboratories, requests for C. difficile assay on fully formed stool will be rejected by the lab (and, probably should have been rejected in this case).

Margaret does have a history of two previous C. difficile infections that required treatment and is at risk for recurrence.  Although her repeat C. difficile toxin test came back positive, it’s important to consider the clinical context; she is asymptomatic, and her positive result may be due to recent treatment of C. difficile infection, rather than an active (current) disease, and requires no treatment. More importantly, in view of her upcoming surgery, in the context of recent C. difficile, extra care should be taken to avoid unnecessary antimicrobial pressure, which could result in a significant risk of recurrent C. difficile. Strategies to reduce her risk of recurrent C. difficile after her next surgery include avoiding unnecessary antibiotics (for example, keeping perioperative antibiotic prophylaxis to the shortest possible course), as well as not testing for, or treating, asymptomatic bacteriuria if it develops post-op.

For information, see first line treatment options (Box, inset) for C. difficile (i.e., in persons who are symptomatic).

The best response:

B. Proceed to direct oral amoxicillin challenge

Local and international guidelines (see ‘Resources’ box) for community-acquired pneumonia [1] strongly recommend amoxicillin 1 g PO TID as treatment of CAP in healthy outpatients. However, we are faced with the common clinical dilemma of a patient with a history of penicillin allergy.

This case highlights a common issue with penicillin allergy labels. Unverified penicillin allergy labels are associated with inappropriate or broad-spectrum antibiotic prescribing, which may result in the development of antibiotic-resistant infections, poor health outcomes and excess health care costs [2,3]. Less than 5% of adult patients labeled with a penicillin allergy are truly allergic. By contrast, over 95% of adult patients reporting a penicillin allergy will have a negative penicillin allergy test result and tolerate subsequent exposure [4].

In 2020, the externally validated PEN-FAST score was created to help non-allergy specialists identify low-risk penicillin allergy in adults [5]. A score lower than 3* (see caveat below) can reliably identify low-risk penicillin allergy with a negative predictive value for a true allergy of 96.3%. The efficacy and safety of this score was shown in the PALACE RCT published in 2023 [6]. The PALACE trial randomly assigned adults labelled with a penicillin allergy scoring lower than 3 on the PEN-FAST tool (i.e.: low risk of positive penicillin allergy test) to receive either a direct oral penicillin challenge or a two-step process of intradermal testing followed by an oral penicillin challenge. Only 1 patient (0.5%) in each arm developed a reaction, which were mild cutaneous reactions resolving after a dose of antihistamine. This trial demonstrates that a direct oral penicillin challenge in an emergency room or outpatient setting is safe in patients with a PEN-FAST score lower than 3 and is as effective as the standard 2-step intradermal test followed by oral challenge. A subsequent prospective study confirmed that implementing a pharmacist-directed beta-lactam oral challenge for low-risk (PEN-FAST score < 3) adult patients can be implemented safely in the Emergency Department [7].

In this case, the PEN-FAST score is 0 (or 1 if the patient could not recall whether symptomatic treatments, such as oral antihistamines, were used). This corresponds to a very low to low risk of a positive penicillin allergy test and a direct oral penicillin challenge with amoxicillin 500 mg PO x 1 can be safely performed in the patient. If there are no immediate reactions within 1h of administration, the allergy label should be removed and the patient can safely proceed with amoxicillin 1 g PO TID for his community-acquired pneumonia.

Option A, referral for penicillin skin testing, is not required here. Note that levofloxacin in option D is too broad spectrum for the treatment of community-acquired pneumonia in an otherwise healthy patient. Doxycycline, option C, is recommended as a second-line agent for community-acquired pneumonia, whereas amoxicillin represents the best therapy if it can be safely provided via an oral challenge, such as in this case. Option E is not recommended – treatment with oral amoxicillin is preferred over no treatment for patients with mild community-acquired pneumonia.

A low-risk allergy label can be effectively and safely delabeled by non-allergy specialist and, therefore, should not be a barrier to receiving the first-line option of amoxicillin for community-acquired pneumonia.

_{*Caveat: For any patients with a previous severe cutaneous adverse reaction (such as Steven-Johnson-Syndrome/Toxic Epidermal Necrolysis), oral penicillin challenge without referral to or discussion with an allergy specialist, is not recommended (even if the PEN-FAST score is < 3). This is, however, a rare scenario.}