From the Guidelines
Broad-spectrum antibiotic coverage against Multi-Drug Resistance (MDR) infections is crucial and can be achieved with options such as carbapenems, which may lead to higher resolution of infections and lower mortality in patients with nosocomial or critically ill patients.
Options for Broad-Spectrum Antibiotic Coverage
- Carbapenems: Initial use of carbapenems may lead to higher resolution of infections and lower mortality in patients with nosocomial or critically ill patients 1.
- Third-generation cephalosporins: Traditionally recommended in all patients with infections, with resolution rates of approximately 90%, but their effectiveness has decreased due to the growing number of infections by MDR organisms 1.
Considerations for Antibiotic Selection
- Local epidemiology: Empirical antimicrobial therapy should be based on local epidemiology, individual patient risk factors for difficult to treat pathogens, clinical severity of infection, and infection source 1.
- Patient risk factors: Previous antimicrobial therapy, acquisition in a healthcare setting, corticosteroid use, organ transplantation, baseline pulmonary or hepatic disease, and recent traveling should be taken into account when selecting antimicrobial therapy 1.
- Infection source: The epidemiology of intra-abdominal flora in critically ill patients with secondary and tertiary abdominal sepsis should be considered, with a prevalence of Gram-positive and Candida in the high gastrointestinal tract and a progressive increase of anaerobes and Gram-negative towards the lower gastrointestinal tracts 1.
Importance of Antibiotic Stewardship
- Narrowing antibiotic coverage: Antibiotic coverage should be narrowed as soon as culture results are available and given for as short a time as possible to prevent the development of resistance 1.
- Avoiding unnecessary use: Unnecessary prolonged use of empiric broad-spectrum antibiotics should be avoided whenever possible to prevent the development of resistance 1.
From the Research
Broad-Spectrum Antibiotic Coverage Options
The following options are available for broad-spectrum antibiotic coverage against Multi-Drug Resistance (MDR) infections:
- Carbapenem-sparing strategies, such as the use of beta-lactam/beta-lactamase inhibitors (e.g., piperacillin-tazobactam) for the treatment of ESBL-producing strains 2
- Combination therapy, including a carbapenem-containing regimen with colistin, high-dose tigecycline, or aminoglycoside, for the treatment of CRE 2
- The use of broad-spectrum antibiotic adjuvants, such as SLAP-S25, to enhance the efficacy of existing antibiotics against MDR Gram-negative pathogens 3
- Newer agents, such as tigecycline, ceftolozane-tazobactam, and ceftazidime-avibactam, which exhibit good activity against MDR Gram-negative bacterial strains 4
- Emerging treatment options, including ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol, for the treatment of MDR Gram-negative bacilli 5
Considerations for Antibiotic Selection
When selecting antibiotics for the treatment of MDR infections, the following factors should be considered:
- The use of broad-spectrum antibiotics should be reserved for cases where the risk of MDR infection is high 4
- Antibiotic selection should be guided by antimicrobial stewardship principles to minimize the development of resistance 4, 5
- Combination therapy may be preferred over monotherapy for the treatment of CRE 2
- The use of antibiotic adjuvants, such as SLAP-S25, may enhance the efficacy of existing antibiotics against MDR Gram-negative pathogens 3
Emerging Treatment Options
Several emerging treatment options are available for the treatment of MDR infections, including:
- Ceftaroline, ceftobiprole, and tedizolid for the treatment of MDR Gram-positive cocci 5
- Ceftolozane-tazobactam, ceftazidime-avibactam, and meropenem-vaborbactam for the treatment of MDR Gram-negative bacilli 5
- Fosfomycin, eravacycline, and plazomicin for the treatment of MDR Gram-negative bacilli 5
- Cefiderocol, a novel siderophore cephalosporin, for the treatment of MDR Gram-negative bacilli 5