Treatment of Bloodstream Infections with Gram-Negative Bacilli

Recommended Treatment Approach

The Infectious Diseases Society of America recommends that patients with gram-negative bacteremia receive empirical antibiotic therapy with agents that have reliable activity against gram-negative bacilli, especially if they are critically ill, have sepsis, are neutropenic, have a femoral catheter, or have a known focus of gram-negative infection 1
For critically ill patients with suspected gram-negative bacteremia and recent colonization or infection with multidrug-resistant (MDR) gram-negative pathogens, two antimicrobial agents of different classes with gram-negative activity should be administered as initial therapy 1
Recommended empiric regimens include carbapenems, antipseudomonal cephalosporins, or piperacillin/tazobactam for broad-spectrum monotherapy 3
Combination therapy with an aminoglycoside plus an antipseudomonal penicillin or extended-spectrum cephalosporin is also recommended 3
The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines recommend more potent agents for treating infections caused by multidrug-resistant gram-negative bacilli 4

Once culture and susceptibility results are available, de-escalation to a single appropriate antibiotic is recommended 1
For persistent bacteremia or severe sepsis despite appropriate therapy, the intravascular device should be removed, and evaluation for endovascular or metastatic infection should be pursued 1
Treatment duration should be 7-14 days for uncomplicated bacteremia, with longer courses needed for complicated infections 1, 2

For patients with neutropenia and gram-negative bacteremia, broad-spectrum antibiotics with reliable gram-negative coverage are essential 3
For catheter-related bloodstream infections with gram-negative bacilli, catheter removal should be considered, especially for infections with certain species 5, 6
For non-HACEK gram-negative bacilli causing endovascular infections, combination therapy with a β-lactam and either an aminoglycoside or fluoroquinolone for 6 weeks is recommended 7

Using inadequate antimicrobial therapy with limited gram-negative coverage (like Augmentin) for bloodstream infections can lead to increased morbidity and mortality 1
Delaying appropriate broad-spectrum antibiotic therapy in patients with suspected gram-negative bacteremia can also lead to poor outcomes 1
Failing to remove infected intravascular devices in cases of persistent bacteremia despite appropriate antimicrobial therapy is another common pitfall 1