What are the treatment choices for Gram-Negative Bacteria (GNB) infections?

From the Guidelines

For the treatment of Gram-negative bacterial (GNB) infections, the most recent and highest quality study recommends using beta-lactam antibiotics such as cephalosporins, carbapenems, or piperacillin-tazobactam as first-line treatment 1. The choice of antibiotic should be guided by local resistance patterns, infection site, patient factors (allergies, renal function), and culture results when available. Some key points to consider in the treatment of GNB infections include:

• Using beta-lactam antibiotics such as cephalosporins (ceftriaxone 1-2g IV daily, cefepime 1-2g IV q8-12h), carbapenems (meropenem 1g IV q8h, imipenem 500mg IV q6h), or piperacillin-tazobactam (4.5g IV q6h) as first-line treatment.
• Considering fluoroquinolones like ciprofloxacin (400mg IV q12h or 500mg PO q12h) or levofloxacin (750mg IV/PO daily) for less severe infections.
• Using aminoglycosides such as gentamicin (5-7mg/kg IV daily) in combination therapy for synergistic effects, particularly for Pseudomonas infections.
• Treatment duration typically ranges from 7-14 days depending on infection site and severity.
• For multidrug-resistant organisms, combinations may be necessary, such as colistin (loading dose 5mg/kg IV, then 2.5mg/kg q12h) with a carbapenem.
• De-escalation to narrower-spectrum antibiotics should occur once susceptibility results are known to reduce resistance development and adverse effects.
• Adequate dosing, monitoring for toxicity (especially with aminoglycosides and colistin), and assessment of clinical response are essential components of effective GNB infection management 1. It is also important to note that the treatment of GNB infections should be individualized based on the specific patient and infection characteristics, and that antibiotic stewardship considerations should be taken into account to minimize the development of resistance and adverse effects 1.

From the FDA Drug Label

Ceftazidime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Gram-negative bacteria • Citrobacter species • Enterobacter species • Escherichia coli • Klebsiella species • Haemophilus influenzae • Neisseria meningitidis • Proteus mirabilis • Proteus vulgaris • Pseudomonas aeruginosa • Serratia species Gram-positive bacteria • Staphylococcus aureus • Streptococcus pneumoniae • Streptococcus pyogenes • Streptococcus agalactiae Anaerobic bacteria • Bacteroides species (Note: many isolates of Bacteroides species are resistant)

Piperacillin and tazobactam for injection is an antibacterial drug [see Microbiology (12.4)].

Treatment choices of drugs for GNB (Gram-Negative Bacteria) include:

• Ceftazidime 2, which is effective against various Gram-negative bacteria such as Pseudomonas aeruginosa, Escherichia coli, and Klebsiella species.
• Piperacillin/Tazobactam 3, which is also an antibacterial drug effective against various Gram-negative bacteria.

It is essential to note that the choice of treatment depends on the specific type of GNB, its susceptibility to the antibiotic, and the patient's clinical condition.

From the Research

Treatment Choices for GNB Infections

The treatment of Gram-negative bacteria (GNB) infections is a growing concern due to limited treatment options and increasing resistance to antibiotics.

• The choice of treatment depends on the type of microorganism, mechanism of resistance, source and severity of infection, as well as pharmacotherapy considerations 4, 5, 6.
• For urinary tract infections (UTIs) caused by antibiotic-resistant GNB, recommended first-line empiric antibiotic therapy includes nitrofurantoin, fosfomycin tromethamine, or pivmecillinam 4.
• Second-line options for UTIs include oral cephalosporins, fluoroquinolones, and β-lactams, such as amoxicillin-clavulanate 4.
• For UTIs due to extended-spectrum β-lactamase-producing (ESBL) Enterobacteriaceae, treatment options include nitrofurantoin, fosfomycin, pivmecillinam, amoxicillin-clavulanate, finafloxacin, and sitafloxacin 4.
• Parenteral treatment options for UTIs due to ESBL-producing Enterobacteriaceae include piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, and ceftolozane-tazobactam 4.

Treatment of Multidrug-Resistant GNB Infections

• The treatment of multidrug-resistant GNB infections requires a complex clinical reasoning, taking into account the peculiar characteristics of the target population, the need for adequate empirical coverage, and the specific enzyme-level activity of novel antimicrobials 6.
• New treatment options, such as ceftazidime/avibactam, meropenem/vaborbactam, and ceftolozane/tazobactam, have become available for the treatment of multidrug-resistant GNB infections 6, 7.
• The optimal use of these new agents should be guaranteed in the long term to delay the emergence and diffusion of resistance 6.
• Antimicrobial stewardship programs should be instituted in all care settings to improve the outcome of infections with multidrug-resistant GNB strains 7.

Recommendations for Treatment

• The British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party makes recommendations for the treatment of infections caused by multidrug-resistant GNB, including the use of intravenous antibiotics and oral agents 7.
• The guidance includes recommendations for stakeholders, including prescribers, and antibiotic-specific recommendations 7.
• Local and national surveillance of antibiotic use, resistance, and outcomes should be supported to inform antibiotic prescribing guidelines 7.