What are the implications of anaerobic Gram-negative (GN) bacteremia?

From the Guidelines

Anaerobic gram-negative bacteremia requires prompt treatment with appropriate antibiotics, and the recommended empiric treatment is metronidazole 500 mg IV every 8 hours or a carbapenem such as meropenem 1 gram IV every 8 hours, especially if mixed infection is suspected. The choice of antibiotic should be based on the clinical condition of the patient, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1. In patients with uncomplicated intra-abdominal infections, a short course of antibiotic therapy (3-5 days) after adequate source control is a reasonable option 1. However, in critically ill patients with ongoing sepsis, an individualized approach should be always mandatory, and patient’s inflammatory response should be monitored regularly 1.

• The major pathogens involved in community-acquired intra-abdominal infections are usual residents of gastrointestinal flora, including Enterobacteriaceae, streptococci, and certain anaerobes (particularly Bacteroides fragilis) 1.
• Narrower spectrum antimicrobial agents are appropriate for these patients, but in CA-IAI patients at risk for extended-spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae infections, anti-ESBL-producer coverage may be warranted 1.
• For patients with healthcare-associated infections (HA-IAIs), antibiotic regimens with broader spectra of activity are preferred, and carbapenem sparing treatment should be recommended particularly in the settings where there is a high incidence of carbapenem resistant K. pneumoniae 1.
• New antibiotics such as ceftolozane/tazobactam and ceftazidime/avibactam have recently been approved for the treatment of IAIs, including infection by ESBLs and P. aeruginosa, and may be valuable for treating infections caused by Gram-negative MDROs in order to preserve carbapenems 1.

Treatment duration typically ranges from 7-14 days depending on the source of infection, clinical response, and resolution of symptoms, but fixed antibiotic durations for GNB bacteraemia do not account for host characteristics or treatment response, and individualized courses guided by C-reactive protein may be a better approach 1. Blood cultures should be obtained before starting antibiotics to identify the specific organism and determine antibiotic susceptibility. Source control is crucial, so any abscesses or infected tissues should be surgically drained or debrided. Common sources of anaerobic bacteremia include intra-abdominal infections, pelvic infections, and oral/dental infections. These bacteria lack the cytochrome systems needed for oxygen metabolism and thus thrive in low-oxygen environments like the colon, female genital tract, and oral cavity. They often produce beta-lactamases, which can inactivate certain antibiotics, making appropriate antibiotic selection essential for effective treatment.

From the Research

Anaerobic Gram Negative Bacteremia

• Anaerobic gram negative bacteremia is a type of infection caused by anaerobic bacteria, which are the most predominant components of the normal human skin and mucous membranes bacterial flora 2.
• These infections can occur in all body locations, including the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin, and soft tissues 2.
• Treatment of anaerobic infections is complicated by their slow growth in culture, polymicrobial nature, and growing resistance to antimicrobials 2, 3.

Treatment Options

• The most effective antimicrobials against anaerobes are metronidazole, carbapenems (imipenem, meropenem, doripenem, ertapenem), chloramphenicol, combinations of a penicillin and a beta-lactamase inhibitor (ampicillin or ticarcillin plus clavulanate, amoxicillin plus sulbactam, piperacillin plus tazobactam), tigecycline, cefoxitin, and clindamycin 2, 3.
• Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, and is effective in treating patients with lower respiratory tract infections, intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia 4, 5.
• New antimicrobial treatment options, such as beta-lactam/beta-lactamase inhibitor combinations, eravacycline, plazomicin, and cefiderocol, are being developed to treat severe or multidrug-resistant Gram-negative infections 6.

Management

• Antimicrobial therapy is frequently the only form of therapy needed, whereas in others it is an important adjunct to drainage and surgery 2.
• Surgical drainage is of primary importance, including debriding of necrotic tissue, draining the pus, improving circulation, alleviating obstruction, and increasing tissue oxygenation 3.
• The primary role of antimicrobials is to limit the local and systemic spread of infection 3.