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How can we effectively treat complicated intra-abdominal infections?

By Noah Engel


 

Case


OLer

LR is a 25F with a PMH most significant for NF1, invasive ductal carcinoma of breast (s/p bilateral breast mastectomy, on chemotherapy), UC (on mesalamine), and developmental delay who presented with abdominal pain.


History

LR started to have R sided and epigastric abdominal pain, which subsequently turned into several episodes of bilious, non-bloody emesis and abdominal distension. Upon presentation to the ED, she had a brown non-bloody liquid bowel movement reminiscent of her past ulcerative colitis flares.


ED Course

Physical Exam: Notable for protuberant abdomen with marked distension. Normal bowel sounds with a soft, non-tender abdomen. Otherwise grossly negative.

 

Vitals: BP: 133/63, Pulse: 70, Temp: 35.5℃, Resp: 18, SpO2: 97% on RA


Laboratory Data:

-       CMP: Normal

-       Urinalysis: Spec Grav > 1.045

-       CBC: WBC value of 16.89 and a neutrophilic predominance of 82.2%

-       CRP: 1.2

-       EKG: normal


Imaging

Impression: Focal areas of wall thickening in the distal ileum; question infectious or inflammatory process.


Treatment

1. Moxifloxacin 400 mg PO q24h (d/t Cefalosporin allergy preventing use of Ceftriaxone)

2. Metronidazole 1g IV q24h


Clinical Question: What is the best course of antibiotics for an immunocompromised patient with an intra-abdominal infection? Why is this the case?


Summary of Evidence

            Treating patients’ infectious processes varies with immune status. In the case of ileitis presented above, immunocompetent patients should not receive empiric antibiotic treatment to preserve the utility of diagnostic procedures and avoid unwarranted side effects.1 Multiple Emergency Medicine guidelines, however, indicate those with compromised immune systems should receive antimicrobial coverage to prevent infection.2, 3

            Literature attests to the microbial diversity of intraabdominal infections. For instance – in one review with over 2600 patients suffering from intra-abdominal infections from over 300 ICUs from around the world – isolated organisms and their respective frequency of isolations were from the following classes: gram-negative bacteria (58.6%), gram-positive aerobic bacteria (39.4%), and anaerobic bacteria (11.7%).4 The wide range of potential pathogens necessitates broad coverage when an immunocompromised patient presents with an infection, as the same study revealed an overall mortality rate of 29.1%.4 Nevertheless, providers who practice antibiotic stewardship must balance the need to sufficiently treat their patients and mitigate the iatrogenicity and antibiotic resistance that accompanies excessive antimicrobial coverage.

            Which antibiotic would provide sufficient coverage for anaerobic bacteria? Several sources indicate metronidazole effectively treats both the most common and causative anaerobic pathogens. For example, the Surgical Infection Society – in its review of nearly 700 peer-reviewed publications – recommended metronidazole paired with an agent directed at aerobic bacteria in nearly all its first-line recommendations. Notably, this study also identified that the plurality (44.4%) of anaerobic intraabdominal infections that resulted in ICU stays were caused by the Bacteroides species.5 Johns Hopkins Hospital designates metronidazole as the first-line agent for this species6 and – in addition to its coverage of other anaerobic bacteria – explains why metronidazole was chosen for the case above.

            What antibiotic would provide appropriate coverage for aerobic bacteria? The guidelines from SIS indicate that cephalosporins would best complement the anaerobic coverage provided by metronidazole. Cephalosporins should serve as the bedrock of aerobic coverage in this context because – compared to fluoroquinolones or piperacillin-tazobactam – they have a comparatively narrow coverage range and less severe side effects.5 Of the antibiotics within the cephalosporin class, ceftriaxone would best serve the JHH-based patient in the clinical vignette, as its coverage profile specified by the antibiogram7 provides adequate coverage against the most common intraabdominal aerobic pathogens without the potentially over-broad coverage provided by cefepime.5

            Which antibiotic would provide sufficient aerobic bacterial coverage for the patient with a documented cephalosporin allergy? UpToDate – an evidence-based clinical resource that cites over 40 peer-reviewed publications in its article on intra-abdominal infections - suggests either monotherapy with piperacillin-tazobactam or a combination therapy of metronidazole and a fluoroquinolone.8 Providers, however, should recognize that piperacillin-tazobactam is a beta-lactam antibiotic and, as such, is likely to elicit a similar allergic reaction to the allergic reaction caused by cephalosporins.9 As such, several guidelines in different geographic regions indicate that – if a patient has an anaphylactic reaction to a cephalosporin – he or she should not receive penicillin antibiotics without proper testing and/or desensitization protocols.10, 11 The choice of a fluoroquinolone also does not come at the expense of effective treatment. Another 2019 meta-analysis of seven randomized controlled trials with over 4000 patients showed that those who received fluoroquinolones in the setting of complicated intraabdominal infections did not have inferior treatment outcomes compared to those who received beta-lactam antibiotics.12

Given the above information, which fluoroquinolone should be provided for the above patient? Guidelines by the SIS indicate that moxifloxacin – with its broad spectrum of coverage – would best complement metronidazole for complicated intra-abdominal infections.5 This is echoed by other analyses of RCTs which state that, unlike other fluoroquinolones, moxifloxacin’s extended anaerobic coverage could prove useful in eliminating anaerobic bacteria not covered by metronidazole.13 Moxifloxacin is also preferable to other fluoroquinolones as gram-negative organisms – namely E. coli – have increasing rates of antibacterial resistance that has yet to translate into resistance patterns for moxifloxacin as of the SIS’s 2019 guidelines.5


Recommendations

-       When presented with an intra-abdominal infection for an immunocompromised patient, one should use metronidazole to cover anaerobic bacteria.

-       Cephalosporins are the best agents to cover both gram-positive and gram-negative aerobic bacteria in intra-abdominal infections, with a preference for ceftriaxone.

-       Fluoroquinolones are an alternative antibiotic choice for aerobic bacteria, although they are considered inferior to cephalosporins because of their broad coverage and side effect profile.

-       When using fluoroquinolones for the treatment of aerobic bacteria in intra-abdominal infections, moxifloxacin should be considered a first-line agent.

-       Piperacillin-tazobactam should be considered after cephalosporin and fluoroquinolone antibiotics for the coverage of aerobic bacteria in abdominal infections.


Citations:

  1. Schertzer, K. A., & Garmel, G. M. (2018). Acute Infectious Diarrhea. Emergency Management of Infectious Diseases: Second Edition, 169–180. https://doi.org/10.1017/9781316597095.027

  2. Patel, D. M., & Riedel, D. J. (2013). Fever in immunocompromised hosts. Emergency Medicine Clinics of North America, 31(4), 1059–1071. https://doi.org/10.1016/j.emc.2013.07.002

  3. Lee, M.C., Perkins, J. (2019). An Introduction: Is My Patient Immunocompromised? How Do I Interpret History and Physical Examination Findings in the Immunocompromised Patient? What Does the Work-Up Look Like for an Immunocompromised Patient? What Are the Unique Risks and Potential Pitfalls?. In: Graham, A., Carlberg, D.J. (eds) Gastrointestinal Emergencies. Springer, Cham. https://doi.org/10.1007/978-3-319-98343-1_111

  4. Blot, S., Antonelli, M., Arvaniti, K., Blot, K., Creagh-Brown, B., de Lange, D., … Davis, N. (2019). Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project. Intensive Care Medicine, 45(12), 1703–1717. https://doi.org/10.1007/s00134-019-05819-3

  5. Mazuski, J. E., Tessier, J. M., May, A. K., Sawyer, R. G., Nadler, E. P., Rosengart, M. R., … Prince, J. M. (2017). The surgical infection society revised guidelines on the management of intra-abdominal infection. Surgical Infections, 18(1). https://doi.org/10.1089/sur.2016.261

  6. Dzintars Pharm.D., BCPS, K., & Pham Pharm.D., P. (2020, January 12). Metronidazole. The Johns Hopkins University. Retrieved from https://www.unboundmedicine.com/ucentral/view/Johns_Hopkins_ABX_Guide/540346/all/Metronidazole

  7. Antibiograms. (2022). In Cosgrove, S. E., & Avdic, E. (Eds.), Guidelines for Antibiotic Use. The Johns Hopkins Hospital (JHH) and Johns Hopkins Health System (JHHS). https://www.unboundmedicine.com/ucentral/view/Guidelines for AntibioticUse/1308128/all/Antibiogram-Anaerobes, JH

  8. Barshak, Miriam Baron. “Antimicrobial Approach to Intra-Abdominal Infections in Adults.” Edited by Stephen B Calderwood and Keri K Hall, UpToDate, UpToDate, 1 Dec. 2023, www.uptodate.com/contents/antimicrobial-approach-to-intra-abdominal-infections-in-adults?search=intraabdominal+infection&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

  9. Romano, A., Gaeta, F., Valluzzi, R. L., Caruso, C., Rumi, G., & Bousquet, P. J. (2010). IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. Journal of Allergy and Clinical Immunology, 126(5), 994–999. https://doi.org/10.1016/j.jaci.2010.06.052

  10. UCDH Pharmacy Therapeutics Committee. “Allergic Cross-Reactivity of Select Antimicrobials - UC Davis Health.” Antimicrobial Stewardship Program at UC Davis, UC Davis, June 2017, health.ucdavis.edu/antibiotic-stewardship/pdfs/abx_cross_reactivity.pdf.

  11. Vancouver Coastal Health, and Providence Health Care. “VCH-PHC Pharmacy Department Antibiotic CROSS-ALLERGY Chart.” Vancouver Coastal Health, Vancouver Coastal Health, May 2021, aspires.vch.ca/Documents/Penicillin%20Allergy/Antibiotic%20Cross-Allergy%20Chart.pdf.

  12. Mavros, M. N., Theochari, N. A., Kyriakidou, M., Economopoulos, K. P., Sava, J. A., & Falagas, M. E. (2019). Fluoroquinolone-based versus β-lactam-based regimens for complicated intra-abdominal infections: a meta-analysis of randomised controlled trials. International Journal of Antimicrobial Agents, 53(6), 746–754. https://doi.org/10.1016/j.ijantimicag.2019.01.004

  13. Goldstein, E. J. C., Solomkin, J. S., Citron, D. M., & Alder, J. D. (2011). Clinical efficacy and correlation of clinical outcomes with in vitro susceptibility for anaerobic bacteria in patients with complicated intra-abdominal infections treated with moxifloxacin. Clinical Infectious Diseases, 53(11), 1074–1080. https://doi.org/10.1093/cid/cir664

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