What are the recommended treatments for complicated infectious diseases, including urinary tract infections and hospital-acquired pneumonia?

From the Guidelines

The most effective treatment for complicated infectious diseases, including urinary tract infections and hospital-acquired pneumonia, involves targeted antimicrobial therapy based on the specific infection, with a focus on newer IPD drugs such as ceftolozane/tazobactam and imipenem/cilastatin/relebactam, as recommended in the most recent guidelines 1.

Treatment Options

For complicated urinary tract infections (UTIs) and hospital-acquired pneumonia (HAP), the following treatment options are recommended:

• For UTIs: Piperacillin/tazobactam, ceftazidime, cefepime, ciprofloxacin, or levofloxacin, with treatment duration of 5-10 days 1.
• For HAP: Ceftolozane/tazobactam, ceftazidime/avibactam, or imipenem/cilastatin/relebactam, with treatment duration of 10-14 days 1.

Key Considerations

• Antimicrobial susceptibility testing results should guide treatment choices, with a focus on targeted therapy to reduce resistance development 1.
• Source control, such as removing infected catheters or draining empyemas, is essential alongside antimicrobial therapy 1.
• Regular monitoring of clinical response, including fever trends, white blood cell counts, and organ function, helps guide treatment adjustments and duration 1.

Newer IPD Drugs

• Ceftolozane/tazobactam and imipenem/cilastatin/relebactam are newer IPD drugs that have shown efficacy in treating complicated infectious diseases, including those caused by multidrug-resistant organisms 1.
• These drugs offer broader coverage and may be used as part of combination therapy to enhance treatment outcomes 1.

From the FDA Drug Label

1. 1. Complicated Urinary Tract Infections (cUTI), including Pyelonephritis VABOMERE® is indicated for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex.
2. INDICATIONS AND USAGE 1. 1 Complicated Urinary Tract Infections (cUTI), including Pyelonephritis ZEMDRI is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by the following susceptible microorganism(s): Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae

The recommended treatments for complicated urinary tract infections (cUTI) include:

• Meropenem-vaborbactam (VABOMERE): for patients 18 years of age and older with cUTI, including pyelonephritis, caused by susceptible microorganisms such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex 2.
• Plazomicin (ZEMDRI): for patients 18 years of age or older with cUTI, including pyelonephritis, caused by susceptible microorganisms such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae, and who have limited or no alternative treatment options 3. Key points:
• These treatments should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
• Culture and susceptibility information should be considered in selecting or modifying antibacterial therapy.
• Local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy in the absence of such data.

From the Research

New IPD Drugs for Complicated Infectious Diseases

• The U.S. Food and Drug Administration (FDA) has approved several new antibiotics with activity against Gram-negative bacteria, including plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam 4.
• These new antibiotics have been shown to be effective in treating complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) 4, 5, 6.
• Ceftazidime-avibactam, a combination of a third-generation cephalosporin and a β-lactamase inhibitor, has been approved for the treatment of cUTI, cIAI, HAP, and other infections caused by aerobic Gram-negative organisms in patients with limited treatment options 5.
• Clinical trials have demonstrated the efficacy and safety of ceftazidime-avibactam in the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, compared to meropenem 7.

Treatment Options for Specific Infections

• For cUTI, treatment options include ceftazidime-avibactam, meropenem-vaborbactam, ceftolozane-tazobactam, and imipenem-relebactam 4, 6.
• For HAP/VAP, treatment options include cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam 4, 6.
• For infections caused by multidrug-resistant Gram-negative bacilli, treatment options include ceftazidime-avibactam, meropenem-vaborbactam, ceftolozane-tazobactam, and cefiderocol, among others 6, 8.

Expert Recommendations

• A panel of experts from the French and Italian Societies of Infectious Diseases has recommended the following treatment options for infections caused by multidrug-resistant Gram-negative bacilli:

• Cefepime for ventilator-acquired pneumonia due to AmpC β-lactamase-producing Enterobacterales
• Ceftazidime-avibactam or cefiderocol combined with fosfomycin for severe pneumonia due to Pseudomonas aeruginosa resistant to ceftolozane-tazobactam
• High-dose piperacillin-tazobactam for cUTI caused by extended-spectrum β-lactamase-producing Enterobacterales
• Ceftolozane-tazobactam or ceftazidime-avibactam plus metronidazole for intra-abdominal infections due to third-generation cephalosporin-resistant Enterobacterales 8.