What is the significance of anaerobic and aerobic blood cultures detecting both Klebsiella pneumoniae and Escherichia coli (E. coli), with a Gram stain showing gram-negative bacilli, in a patient with sepsis and a normal white blood cell (WBC) count?

From the Guidelines

The patient with sepsis due to polymicrobial bloodstream infection with Klebsiella pneumoniae and Escherichia coli should be immediately started on broad-spectrum antibiotic therapy with a carbapenem such as meropenem 1 gram IV every 8 hours or piperacillin-tazobactam 4.5 grams IV every 6 hours, as recommended by the Surviving Sepsis Campaign guidelines 1. This approach is crucial given the high morbidity and mortality associated with sepsis and septic shock, especially when the causative pathogens are not promptly and effectively treated. The choice of empiric antimicrobial therapy depends on various factors including the patient's history, clinical status, and local epidemiologic factors, but in cases of suspected sepsis or septic shock, broad-spectrum coverage is recommended to ensure that all likely pathogens are covered 1.

Key Considerations

• The patient's normal white blood cell count does not exclude sepsis, as some patients, particularly those who are immunocompromised, may not mount a typical inflammatory response.
• Source identification is crucial, with common sources for these organisms including urinary tract, intra-abdominal, and biliary infections.
• Additional workup should include urinalysis, abdominal imaging, and evaluation of indwelling devices if present.
• The polymicrobial nature of this infection suggests a gastrointestinal or genitourinary source, as these are common sites where both organisms colonize.

Management Approach

• Immediate initiation of broad-spectrum antibiotic therapy is essential, with the option to narrow down the therapy once antibiotic susceptibility results are available, typically within 48-72 hours.
• Treatment duration should be 7-14 days, depending on source control and clinical response.
• Close monitoring for signs of septic shock, including hypotension, tachycardia, and altered mental status, is necessary.
• Fluid resuscitation with crystalloids (30 ml/kg) should be administered if hypotension develops.

Evidence-Based Practice

The recommendation for broad-spectrum antibiotic therapy in sepsis is supported by guidelines that emphasize the importance of prompt and effective treatment to reduce morbidity and mortality 1. These guidelines also highlight the need for obtaining appropriate routine microbiologic cultures before starting antimicrobial therapy, if possible, to guide the selection of antimicrobial agents and to ensure that the chosen therapy is effective against the causative pathogens.

From the FDA Drug Label

AVYCAZ has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections ... Aerobic Bacteria Gram-negative Bacteria ... Escherichia coli Klebsiella pneumoniae AVYCAZ demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA).

The patient has sepsis with anaerobic and aerobic blood cultures detecting both Klebsiella pneumoniae and E. coli. Avibactam (component of AVYCAZ) has been shown to be active against Klebsiella pneumoniae and E. coli in the presence of certain beta-lactamases. Therefore, AVYCAZ may be effective against the bacteria detected in the patient's blood cultures 2.

Piperacillin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections ... Aerobic gram-negative microorganisms ... Escherichia coli Klebsiella species

Piperacillin has been shown to be active against E. coli and Klebsiella species 3. However, the effectiveness of piperacillin against the specific strains of Klebsiella pneumoniae and E. coli detected in the patient's blood cultures is unknown.

Key points:

• AVYCAZ may be effective against Klebsiella pneumoniae and E. coli.
• Piperacillin has been shown to be active against E. coli and Klebsiella species, but its effectiveness against the specific strains detected in the patient's blood cultures is unknown.

From the Research

Patient Condition

The patient has sepsis with both anaerobic and aerobic blood cultures detecting Klebsiella pneumoniae and E. coli. The Gram stain shows gram-negative bacilli, and the patient has a normal white blood cell (WBC) count.

Treatment Options

• The study 4 compared the effectiveness of piperacillin-tazobactam and meropenem in treating bloodstream infections caused by E. coli or Klebsiella pneumoniae with ceftriaxone resistance. The results showed that piperacillin-tazobactam was not noninferior to meropenem in terms of 30-day mortality.
• Another study 5 investigated the in vitro activity of taniborbactam combined with cefepime or meropenem against Klebsiella pneumoniae and Pseudomonas aeruginosa metallo-beta-lactamase-producing clinical isolates. The results suggested that the combinations cefepime-taniborbactam and meropenem-taniborbactam are promising alternative treatment options for infections caused by metallo-beta-lactamase-producing isolates.
• The study 6 described the protocol for a randomized controlled trial comparing meropenem and piperacillin-tazobactam for the definitive treatment of bloodstream infections due to ceftriaxone non-susceptible E. coli and Klebsiella spp.
• The study 7 evaluated the in vitro efficacy of aztreonam in combination with ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/relebactam against multidrug-resistant, metallo-β-lactamase-producing Klebsiella pneumoniae. The results showed that synergy was observed in 97.5% of the combinations ceftazidime/avibactam-aztreonam and imipenem/relebactam-aztreonam.
• The study 8 investigated the in vitro and in vivo activities of piperacillin-tazobactam and meropenem at different inoculum sizes of ESBL-producing Klebsiella pneumoniae. The results showed that meropenem was more resistant to the inoculum effect of ESBL-Kpn than piperacillin-tazobactam both in vitro and in vivo.

Key Findings

• Meropenem may be a more effective treatment option than piperacillin-tazobactam for bloodstream infections caused by E. coli or Klebsiella pneumoniae with ceftriaxone resistance 4, 8.
• The combination of taniborbactam with cefepime or meropenem may be a promising alternative treatment option for infections caused by metallo-beta-lactamase-producing isolates 5.
• Aztreonam in combination with ceftazidime/avibactam, meropenem/vaborbactam, or imipenem/relebactam may be effective against multidrug-resistant, metallo-β-lactamase-producing Klebsiella pneumoniae 7.