Beta-lactams;

My elderly patient with UTI and E. coli bacteremia is ready to be switched from IV to oral antibiotic. Can I consider an oral beta-lactam in place of a fluoroquinolone or trimethoprim-sulfamethoxazole to complete an adequate course of antibiotic therapy at home.

FA Manian MD, MPH, , , , , , , , Leave a comment

Although oral fluoroquinolones (FQs) and trimethoprim-sulfamethoxazole (TMP-SMX) have been routinely recommended as step-down therapy for treatment of Enterobacterales bacteremia owing to their high bioavailability, increasing evidence suggests that beta-lactam (BL) antibiotics (particularly those with high bioavailability, such as cephalexin) are as effective without the attendant adverse risks associated with FQs—with increasing FDA warnings—and TMP-SMX.1,2

In the largest study to date involving a retrospective review of over 4,000 cases of Enterobacterales UTI-associated bacteremia (eg, E. coli, Proteus spp., Klebsiella spp) in Veterans Affairs hospitals, no significant difference in the main outcome (composite of 30-day all cause mortality or 30-day recurrent bacteremia) was found between the oral beta-lactam and FQ/TMP-SMX groups (4.4% vs 3.0%, respectively); additionally, when examined separately, no significant difference in mortality (3.0% vs 2.6%) or recurrent bacteremia (1.5% vs 0.4%) was found. 1

A meta-analysis of 8 retrospective studies (2019) also failed to find a significant difference in mortality or recurrent bacteremia between BLs and FQs or TMP-SMX groups; it did find a higher odds of any recurrent infection, however (5.5% vs 2.0% (O.R. 2.06, 1.18-3.61). 2

Before selecting an antibiotic, however, it’s important to recall that not all oral BLs are  created equal, with some having better bioavailability than others.   More specifically, it may not be common knowledge that cephalexin (“Keflex”), a commonly prescribed and inexpensive cephalosporin with great safety profile, has 90-100% bioavailability, rivaling those of FQs or TMP-SMX.

 Of interest, in a subset of patients who received cephalexin as step-down therapy (n=245) in the VA study above, the outcomes were nearly identical to those who received FQ or TMP-SMX, with a 30-d recurrent bacteremia of 0% and a 30-day mortality of 2% (vs 0.4% and 2.5% for ciprofloxacin and 1.0% and 2.4% for TMP-STX, respectively). Of note nearly one-half of the cephalexin group received a higher dose of 500 mg 4x/day, with the rest receiving less frequent dosing. 

These findings makes one wonder whether suboptimal oral BL dosing may not have contributed to the discrepant results from earlier studies suggesting the superiority of FQs or TMP-SMX over oral BLs as step-down therapy. 1,2

 

Bonus Pearl: Did you know that cephalexin may be given up to 4 gm/day in 4 divided doses with 90% of the drug excreted unchanged in the urine? 3

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Sutton JD, Stevens VW, Chang NCN, Khader K, et al. Oral beta-lactam antibiotics vs fluoroquinolones or trimethoprim-sulfamethoxazole for definite treatment of Enterobacterales bacteremia from a urine source. JAMA Network Open 2020;3 (10):e20220166. Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source – PubMed (nih.gov)
  2. Punjabi C, Tien V, Meng L, et al. Oral fluoroquinolone or trimethoprim-sulfamethoxazole vs beta-lactams as step-down therapy for Enterobacteriaceae bacteremia: systematic review and meta-analysis. Open Forum Infect Dis 2019;6:ofz364 doi:10.1.1093/ofid/ofz364   https://pubmed.ncbi.nlm.nih.gov/31412127/
  3. Herman TF, Hasmi MF. Cephalexin. StatPearls (internet). https://www.ncbi.nlm.nih.gov/books/NBK549780/ Accessed July 10, 2022.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My elderly patient with UTI and E. coli bacteremia is ready to be switched from IV to oral antibiotic. Can I consider an oral beta-lactam in place of a fluoroquinolone or trimethoprim-sulfamethoxazole to complete an adequate course of antibiotic therapy at home.

What changes should I consider in my treatment of hospitalized patients with community-acquired pneumonia (CAP) in light of the 2019 guidelines of the American Thoracic society (ATS) and Infectious Diseases Society of America (IDSA)?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Compared to 2007,1 the 2019 ATS/IDSA guidelines2 propose changes in at least 4 major areas of CAP treatment in inpatients, with 2 “Do’s” and 2 “Dont’s”:

  • Do select empiric antibiotics based on severity of CAP and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (see related pearl on P4P)
  • Do routinely treat CAP patients who test positive for influenza with standard CAP antibiotics
  • Don’t routinely provide anaerobic coverage in aspiration pneumonia (limit it to empyema and lung abscess) (see related pearl on P4P)
  • Don’t routinely treat CAP with adjunctive corticosteroids in the absence of refractory shock

β-lactam plus macrolide is recommended for both non-severe and severe CAP.  β-lactam plus respiratory fluoroquinolone is an alternative regime in severe CAP, though not endorsed as strongly as β-lactam plus macrolide therapy (low quality of evidence).  Management per CAP severity summarized below:

  • Non-severe CAP
    • β-lactam (eg, ceftriaxone, cefotaxime, ampicillin-sulbactam and newly-added ceftaroline) plus macrolide (eg, azithromycin, clarithromycin) OR respiratory fluoroquinolone (eg, levofloxacin, moxifloxacin)
    • In patients at risk of MRSA or P. aeruginosa infection (eg, prior isolation of respective pathogens, hospitalization and parenteral antibiotics in the last 90 days or locally validated risk factors—HCAP has been retired), obtain cultures/PCR
    • Hold off on MRSA or P. aeruginosa coverage unless culture/PCR results return positive.
  • Severe CAP
    • β-lactam plus macrolide OR β-lactam plus respiratory fluoroquinolone (see above)
    • In patients at risk of MRSA or P. aeruginosa infection (see above), obtain cultures/PCR
    • Add MRSA coverage (eg, vancomycin or linezolid) and/or P. aeruginosa coverage (eg, cefepime, ceftazidime, piperacillin-tazobactam, meropenem, imipenem) if deemed at risk (see above) while waiting for culture/PCR results

Duration of antibiotics is for a minimum of 5 days for commonly-targeted pathogens and a minimum of 7 days for MRSA or P. aeruginosa infections, irrespective of severity or rapidity in achieving clinical stability.

For patients who test positive for influenza and have CAP, standard antibacterial regimen should be routinely added to antiinfluenza treatment.

For patients suspected of aspiration pneumonia, anaerobic coverage (eg, clindamycin, ampicillin-sulbactam, piperacillin-tazobactam) is NOT routinely recommended in the absence of lung abscess or empyema.

Corticosteroids are NOT routinely recommended for non-severe (high quality of evidence) or severe (moderate quality of evidence) CAP in the absence of refractory septic shock.

Related pearls on P4P:

2019 CAP guidelines on diagnostics:                                        https://pearls4peers.com/2020/02/14/what-changes-should-i-consider-in-my-diagnostic-approach-to-hospitalized-patients-with-community-acquired-pneumonia-cap-in-light-of-the-2019-guidelines-of-the-american-thoracic-society-ats-and-inf/ 

Anerobic coverage of aspiration pneumonia: https://pearls4peers.com/2019/07/31/should-i-routinely-select-antibiotics-with-activity-against-anaerobes-in-my-patients-with-presumed-aspiration-pneumonia/

References

  1. Mandell LA, Wunderink RG, Anzueto A. Infectious Disease Society of America/American Thoracic Society Consensus Guidelines on the Management guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27-72. https://www.ncbi.nlm.nih.gov/pubmed/17278083
  2. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. Am J Respir Crit Care Med 2019;200:e45-e67. https://www.ncbi.nlm.nih.gov/pubmed/31573350

 

What changes should I consider in my treatment of hospitalized patients with community-acquired pneumonia (CAP) in light of the 2019 guidelines of the American Thoracic society (ATS) and Infectious Diseases Society of America (IDSA)?

Should empiric coverage of Staphylococcus aureus bacteremia (SAB) routinely include an anti-staphyloccal β-lactam?

FA Manian MD, MPH, , , Leave a comment

Although there are no clinical trials comparing  therapy with vancomycin and β-lactam to vancomycin alone in the empiric treatment of S. aureus bacteremia (SAB), combination therapy has been advocated by some based on reports of reduced morbidity and mortality (1). More recently however, a retrospective study involving 122 hospitals failed to find superiority of vancomycin-β-lactam combination therapy compared to vancomycin alone for empiric therapy of SAB (2).

We do know that despite its activity against methicillin-susceptible S. aureus (MSSA), vancomycin is less bactericidal (3), with a higher rate of relapse than anti-staphylococcal β-lactams in the treatment of established SAB (4).

So although it may not be clear if we need to empirically place all of our patients suspected of SAB on a vancomycin-β-lactam from the get go,  once MSSA has been confirmed, vancomycin should be dropped in favor of an anti-staphylococcal β-lactam.

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References 

  1. McConeghy KW, Bleasdale SC, Rodvold KA. The empirical combination of vancomycin and a β-lactam for staphylococcal bacteremia. Clin Infect Dis 2013;57:1760-5. https://www.ncbi.nlm.nih.gov/pubmed/23985343
  2. McDaniel JS, Perencevich EN, Diekema DJ, et al. Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals. Clin Infect Dis 2015;61:361-7. https://www.ncbi.nlm.nih.gov/pubmed/25900170 
  3. Fernandez Guerrero ML, de Gorgolas M. Comparative activity of cloxacillin and vancomycin against methicillin-susceptible Staphylococcus aureus experimental endocarditis. J Antimicrob Chemother 2006;58:1066-1069. https://www.ncbi.nlm.nih.gov/pubmed/16931540
  4. Chang F-Y, Peacock JE, Musher DM, et al. Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 2003;82:333-9. https://www.ncbi.nlm.nih.gov/pubmed/14530782
Should empiric coverage of Staphylococcus aureus bacteremia (SAB) routinely include an anti-staphyloccal β-lactam?