Clinical Case

History of Present Illness: A 59-year old male reports to the hospital after a 2-day history of “excruciating pain” in his right lower abdomen.

Past Medical History: Hypertension, hyperlipidemia, type 2 diabetes mellitus, depression

Social History: Drinks 6-8 beers per week according to his wife

Current Medications: amlodipine, lovastatin, venlafaxine, sertraline, glargine insulin, metformin, empagliflozin

Allergies: ampicillin (mild rash several days into treatment); trimethoprim-sulfamethoxazole (nausea)

Vital Signs: Temperature 100.8°F (37.8°C); heart rate 118 beats/minute; respiratory rate 24 breaths/minute; blood pressure 90/50 mm Hg; SpO2 (arterial oxygen saturation) 94% on 2 L

Lab Values: WBC 18.8 x 10³ cells/mm³ (SI 18.8 x 10⁹ cells/L); Hgb 12.1 g/dL (SI 121 g/L); Hct 43.4% (SI 0.434); Na 140 mEq/L (SI 140 mmol/L); K 3.5 mEq/L (SI 3.5 mmol/L); Cl 98 mEq/L (SI 98 mmol/L); HCO₃ 23 mEq/L (SI 23 mmol/L); glucose 189 mg/dL (SI 10.49 mmol/L); calcium 9.5 mg/dL (SI 2.4 mmol/L); SCr 1.3 mg/dL (SI 114.92 micromoles/L); phosphorus 2.3 mg/dL (SI 0.74 mmol/L); magnesium 1.5 mEq/L (SI 0.75 mmol/L)

Procedure Data: CT scan suggestive of peritonitis due to a perforated appendix

Blood cultures: pending

Other Data: N/A

Question 1

Which antimicrobial therapy is most appropriate empirically?

1. Ampicillin-sulbactam
2. Cefazolin plus clindamycin
3. Cefepime plus metronidazole
4. Levofloxacin plus clindamycin

Answer: 3. Cefepime plus metronidazole

Rationale: Cefepime plus metronidazole (answer choice 3) is the most appropriate answer choice of those listed and follows in line most closely with the IDSA guidelines. Ampicillin-sulbactam, answer choice 1, is not recommended for use because of high rates of resistance to this agent among community-acquired E. coli. Clindamycin is not recommended for use because of increasing prevalence of resistance to these agents among the Bacteroides fragilis group (answer choice 2 and 4).

Citation:  Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:133.

Question 2

The patient is started on meropenem and vancomycin. On hospital day 3, culture results from the abdominal fluid indicate ampicillin-susceptible Enterococcus faecalis and pan-susceptible E. coli. What is best course of action given this finding?

1. Continue both antibiotics
2. Stop vancomycin, continue meropenem
3. Switch to piperacillin-tazobactam
4. Switch to trimethoprim-sulfamethoxazole

Answer: 3. Switch to piperacillin-tazobactam

Rationale: The patient can be appropriately de-escalated in this case to piperacillin-tazobactam monotherapy (answer choice 3). Patient’s history of mild rash with ampicillin in the past does not preclude use of penicillins. Given that susceptibilities have returned, answer choice 1, is inappropriate. Moreover, answer choice 2, continue meropenem is also inappropriate as the E. coli isolate is pan-susceptible. Answer choice 4, is incorrect as trimethoprim-sulfamethoxazole is not active against Enterococcus faecalis.

Citation: Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:133.

Question 3

After an additional washout, the patient is discharged on meropenem for 3 weeks. He reports to an emergency department at an outside hospital 2 days after completing the meropenem with fever and weakness. The physician suspects residual infection associated with his recent surgery. Which therapy would be most appropriate today?

1. Colistin
2. Eravacycline
3. Plazomicin
4. Restart meropenem

Answer: 2. Eravacycline

Rationale: Answer choice 2, eravacycline, is likely to be active against most intraabdominal pathogens including multidrug-resistant pathogens. Given the exposure to carbapenems, drug resistance is likely. Answer choice 3, plazomicin, is inappropriate as monotherapy and would be limited in its spectrum of activity for intraabdominal organisms. Answer choice 4, restart meropenem, is inappropriate due to the potential for carbapenem resistance given the duration of therapy and the recent prolonged course. Answer choice 1, colistin, is considered a drug of last resort and is rarely appropriate empirically.

Citation: Heaney M, Mahoney MV, Gallagher JC. Eravacycline: the tetracyclines strike back. Ann Pharmacother 2019; 53:1124–35.

Question 4

An abdominal abscess is seen on imaging. The abscess is drained and culture results indicate an Enterobacter cloacae which is resistant to carbapenems. Which drug is most likely to be active?

1. Ceftaroline plus aztreonam
2. Ceftolozane-tazobactam
3. Lefamulin
4. Meropenem-vaborbactam

Answer: 4. Meropenem-vaborbactam

Rationale: Meropenem-vaborbactam, answer choice 4, is most likely to be active against most carbapenem-resistant Enterobacter isolates. In contrast, ceftolozane-tazobactam (answer choice 2) may be active, but is variable and susceptibilities should be confirmed before considering its use. Answer choice1, ceftaroline plus aztreonam is inappropriate with aztreonam plus ceftazidime-avibactam being employed for metallo-beta-lactamase producing isolates, not ceftaroline plus aztreonam. Lefamulin, answer choice 3, is not active against Enterobacterales.

Citation: Zhanel GG, Lawrence CK, Adam H, et al. Imipenem-relebactam and meropenem-vaborbactam: two novel carbapenem-beta-lactamase inhibitor combinations. Drugs. 2018;78(1):65–98.

Question 5

The patient is started on meropenem-vaborbactam. The addition of vaborbactam expands activity against which type of organism?

1. Carbapenem-resistant E. coli
2. Carbapenem-resistant Pseudomonas aeruginosa
3. OXA-48 producing Enterobacterales
4. Stenotrophomonas maltophilia.

Answer: 1.      Carbapenem-resistant E. coli

Rationale: Vaborbactam does not restore activity against carbapenem-resistant Pseudomonas, making answer choice 2 incorrect. Answer choice 4, Stenotrophomonas, is inherently resistant to carbapenems due to inherent metallo-beta-lactamase production. Vaborbactam is also unable to restore the activity of meropenem against this organism. Answer choice 3, vaborbactam does not restore activity; however, avibactam would. Vaborbactam restores the activity of meropenem against carbapenem-resistant Enterobacterales (answer choice 1).

Citation: Zhanel GG, Lawrence CK, Adam H, et al. Imipenem-relebactam and meropenem-vaborbactam: two novel carbapenem-beta-lactamase inhibitor combinations. Drugs. 2018;78(1):65–98.