What is the empiric coverage for Gram-negative rods (GNR) in bacteremia?

From the Guidelines

For empiric coverage of gram-negative rods in blood, I recommend starting with a broad-spectrum carbapenem such as meropenem 1g IV every 8 hours, as it provides broad coverage against most pathogens isolated in healthcare-associated infections, including resistant gram-negative bacilli 1. When selecting empiric antimicrobial therapy, several factors must be considered, including the anatomic site of infection, prevalent pathogens within the community and hospital, resistance patterns, and the presence of specific immune defects or risk factors for multidrug-resistant pathogens.

• The choice of empiric antimicrobial regimens in patients with sepsis and septic shock is complex and cannot be reduced to a simple table, but general suggestions can be provided, such as using a broad-spectrum carbapenem or extended-range penicillin/β-lactamase inhibitor combination 1.
• Multidrug therapy is often required to ensure a sufficiently broad spectrum of empiric coverage initially, and clinicians should be cognizant of the risk of resistance to broad-spectrum β-lactams and carbapenems among gram-negative bacilli in some communities and healthcare settings 1.
• The addition of a supplemental gram-negative agent to the empiric regimen is recommended for critically ill septic patients at high risk of infection with multidrug-resistant pathogens, such as Pseudomonas or Acinetobacter, to increase the probability of at least one active agent being administered 1.
• Blood cultures should be obtained before starting antibiotics whenever possible, and therapy should be narrowed once culture and sensitivity results are available, to provide coverage against common gram-negative pathogens including Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa 1.

From the FDA Drug Label

Tigecycline has been shown to be active against most of the following microorganisms, both in vitro and in clinical infections... Gram-negative bacteria Citrobacter freundii Enterobacter cloacae Escherichia coli Haemophilus influenzae Klebsiella oxytoca Klebsiella pneumoniae Colistimethate sodium is a surface active agent which penetrates into and disrupts the bacterial cell membrane It has been shown to have bactericidal activity against most strains of the following microorganisms, both in vitro and in clinical infections... Aerobic gram-negative microorganisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa

Empiric coverage for gram-negative rods in blood can be achieved with tigecycline or colistin, as both have shown activity against various gram-negative bacteria, including:

• Tigecycline: Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae
• Colistin: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa 2 3

From the Research

Empiric Coverage for Gram-Negative Rods in Blood

• The choice of empiric therapy for gram-negative rods in blood has become increasingly difficult due to the increasing incidence of antibiotic-resistant bacteria 4.
• Current diagnostic and treatment guidelines suggest that all seriously ill patients in whom infection is suspected undergo a comprehensive work-up to confirm the etiology prior to initiation of antibiotic therapy 4.
• Empiric therapy for many nosocomial infections must be directed at multi-drug-resistant, gram-negative bacilli, especially in patients with a history of prolonged hospitalization and recent antibiotic use 4.
• Meropenem is a broad-spectrum antibacterial agent that is indicated as empirical therapy prior to the identification of causative organisms, or for disease caused by single or multiple susceptible bacteria in both adults and children with a broad range of serious infections, including those caused by gram-negative rods 5.
• Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity encompassing most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases, and is useful for the treatment of patients with polymicrobial infections caused by aerobic or anaerobic beta-lactamase-producing bacteria 6.
• The initial empiric antibiotic therapy should have activity against typical gram-positive and gram-negative causative micro-organisms, and anaerobic coverage should be provided for intra-abdominal infections or others where anaerobes are significant pathogens 7.
• A beta-lactam plus an aminoglycoside is the standard for treating severe Pseudomonas aeruginosa infections, but the fluoroquinolones are safer and have been widely used as an alternative to the aminoglycosides in this setting 8.
• The degree of synergy between a beta-lactam plus aminoglycoside and a beta-lactam plus fluoroquinolone seems to be comparable, and there is a similar rate of synergy among different fluoroquinolone-based combinations 8.

Antibiotic Options

• Meropenem is an option for the empirical treatment of serious bacterial infections in hospitalized patients, including those caused by gram-negative rods 5.
• Piperacillin/tazobactam is an effective treatment for patients with lower respiratory tract, intra-abdominal, urinary tract, gynaecological and skin/soft tissue infections, and for fever in patients with neutropenia 6.
• Cefepime, piperacillin/tazobactam, gentamicin, ciprofloxacin, and levofloxacin alone and in combination have been studied against Pseudomonas aeruginosa, and the results suggest that these antibiotics can be effective against gram-negative rods 8.

Treatment Considerations

• Early administration of broad-spectrum antimicrobial drugs is one of the most important treatments for patients with sepsis or septic shock, and drugs should be initiated as soon as possible 7.
• The choice of empiric antimicrobials should take into account patient factors, common local pathogens, hospital antibiograms and resistance patterns, and the suspected source of infection 7.
• Antimicrobial agent therapy should be de-escalated as soon as possible 7.