What alternative antibiotics are recommended for a patient with pneumonia who has failed treatment with intravenous (IV) ceftriaxone (Ceftriaxone)?

From the Guidelines

For a patient who has failed IV ceftriaxone for pneumonia, switching to piperacillin-tazobactam (4.5g IV every 6 hours) or meropenem (1g IV every 8 hours) is recommended, as these antibiotics provide broader coverage against potential resistant organisms, including Pseudomonas and MRSA, as suggested by the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society 1. When considering alternative antibiotics, it's essential to take into account the patient's risk of mortality, factors increasing the likelihood of MRSA, and local resistance patterns.

• For patients not at high risk of mortality and without factors increasing the likelihood of MRSA, options include piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem, as outlined in the guidelines 1.
• For patients at high risk of mortality or with recent intravenous antibiotic use, a combination of two antibiotics, avoiding two β-lactams, is recommended, with options including piperacillin-tazobactam, cefepime, levofloxacin, imipenem, meropenem, and vancomycin for MRSA coverage, as per the guidelines 1. It's crucial to obtain cultures before changing antibiotics to identify the causative organism and its susceptibilities, and to consider adding coverage for atypical pathogens if not previously included.
• Treatment duration should be guided by clinical improvement, typically ranging from 5-7 days for community-acquired pneumonia to 7-14 days for hospital-acquired pneumonia.
• If the patient continues to deteriorate despite broadened antibiotic coverage, reassess the diagnosis and consider pulmonary consultation, as treatment failure may indicate resistant organisms, inadequate drug levels, or a non-infectious cause of symptoms, as suggested by the guidelines 1.

From the FDA Drug Label

Table 13: Clinical Cure Rates at TOC from Two Adult Phase 3 CABP Trials Teflaro n/N (%)Ceftriaxone n/N (%)Treatment Difference (2-sided 95% CI) CABP Trial 1 CE194/224 (86.6%)183/234 (78.2%)8.4 (1.4,15.4) MITTE244/291 (83.8%)233/300 (77.7%)6.2 (-0.2,12.6) CABP Trial 2 CE191/232 (82.3%)176/229 (76.9%)5.4 (-2.3,13.1)

Alternative Antibiotics:

• Ceftaroline may be considered as an alternative for patients who have failed IV ceftriaxone for pneumonia, as it has shown clinical cure rates comparable to ceftriaxone in CABP trials 2.
• However, it is essential to note that the FDA label does not provide direct guidance on the use of ceftaroline as a salvage therapy for ceftriaxone failure.
• The decision to use ceftaroline should be based on individual patient factors, such as the causative pathogen, disease severity, and local resistance patterns.
• Other antibiotics may also be considered as alternatives, but their selection should be guided by susceptibility patterns and clinical judgment.

From the Research

Alternative Antibiotic Options

If a patient has failed IV ceftriaxone for pneumonia, alternative antibiotic options can be considered. The choice of antibiotic depends on various factors, including the severity of the infection, the patient's underlying health conditions, and the susceptibility of the causative organism to different antibiotics.

Broad-Spectrum Antibiotics

• Piperacillin/tazobactam has been shown to be effective in the treatment of hospital-acquired pneumonia, including cases where ceftriaxone is not effective 3.
• Ceftriaxone at a higher dose (2g daily) may be considered for ICU patients with lower mortality risk 4.
• Combination therapy with levofloxacin and ceftriaxone has been shown to attenuate lung inflammation in a mouse model of bacteremic pneumonia caused by multidrug-resistant Streptococcus pneumoniae 5.

Network Meta-Analysis

A network meta-analysis of empiric antibiotics for community-acquired pneumonia in adult patients found that:

• Ceftaroline and piperacillin/tazobactam have the highest probability of being the best option for cure rate 6.
• Ceftriaxone plus levofloxacin, ertapenem, and amikacin plus clarithromycin have the highest probability of being the best option for mortality rate 6.

Considerations

When selecting an alternative antibiotic, it is essential to consider the patient's individual needs, the severity of the infection, and the potential for antibiotic resistance. Consultation with an infectious disease specialist or a clinical pharmacist may be helpful in making an informed decision.