Classification and Treatment of Gram-Positive Cocci (GPC) and Gram-Negative Bacilli (GNB)
Microbiological Classification
Gram-Positive Cocci (GPC)
GPC include methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci (VRE), methicillin-sensitive S. aureus (MSSA), coagulase-negative staphylococci, and Streptococcus species. 1 These organisms have emerged as increasingly common causes of healthcare-associated infections, now representing up to 55% of spontaneous bacterial peritonitis cases in cirrhotic patients. 2
Gram-Negative Bacilli (GNB)
GNB encompass carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and extensively drug-resistant Acinetobacter baumannii (CRAB), along with susceptible strains of E. coli, Klebsiella pneumoniae, and other Enterobacterales. 3 The WHO has designated carbapenem-resistant organisms as critical priority pathogens, with CRAB and carbapenem-resistant K. pneumoniae causing over 50,000 deaths annually attributed to antimicrobial resistance. 3
Risk Stratification for Empiric Therapy Selection
Identify high-risk patients requiring broad-spectrum coverage based on: prior MDR organism infection/colonization within 90 days, recent antibiotic exposure (especially carbapenems, broad-spectrum cephalosporins, fluoroquinolones), hospitalization >2 days in past 90 days, current hospitalization ≥5 days, hemodialysis dependence, poor functional status, and immunosuppression. 4 Prior carbapenem or fluoroquinolone use specifically increases risk for MDR Pseudomonas aeruginosa. 4
Treatment Approach by Pathogen Type
Gram-Positive Cocci Treatment
MRSA and MSSA
- For acute bacterial skin and skin structure infections (ABSSSI): Use dalbavancin, oritavancin, telavancin, or daptomycin as first-line agents. 1
- For community-acquired pneumonia: Ceftaroline, linezolid, or tigecycline are formally approved options. 1
- For MSSA infections: Penicillin, cloxacillin, or erythromycin cover 90% of Gram-positive infections with narrow spectrum activity. 5
Vancomycin-Resistant Enterococci (VRE)
- For pneumonia: Linezolid 600 mg IV every 12 hours for at least 7 days (strong recommendation). 6
- For bloodstream infections: Linezolid 600 mg IV every 12 hours for 10-14 days (strong recommendation). 6
- For complicated intra-abdominal infections: Linezolid 600 mg IV every 12 hours for 5-7 days (strong recommendation). 6
Gram-Negative Bacilli Treatment
Carbapenem-Resistant Enterobacterales (CRE)
For bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP): Use ceftazidime-avibactam 2.5g IV every 8 hours infused over 3 hours as first-line therapy. 6, 7 This agent demonstrates superior clinical cure rates of 83-86% compared to polymyxin-based regimens. 7
For complicated urinary tract infections: Choose ceftazidime-avibactam 2.5g IV every 8 hours, meropenem-vaborbactam 4g IV every 8 hours, or imipenem-cilastatin-relebactam 1.25g IV every 6 hours. 6
For uncomplicated urinary tract infections: Use fosfomycin 3g PO single dose OR 3g PO every other day for 3-7 days. 6
When newer agents are unavailable: Use polymyxin B or colistin-based combination therapy with two in vitro active agents (polymyxin + carbapenem if MIC ≤8 mg/L, polymyxin + fosfomycin, or polymyxin + aminoglycoside). 7 Combination therapy reduces 28-30 day mortality compared to monotherapy (35.7% vs 55.5%; OR 0.46,95% CI 0.30-0.69). 7
Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)
Use ceftolozane-tazobactam as the preferred agent for MDR Pseudomonas aeruginosa infections. 4 This recommendation is based on its superior activity against difficult-to-treat resistant strains.
Carbapenem-Resistant Acinetobacter baumannii (CRAB)
For pneumonia: Use colistin-based combination therapy with or without carbapenem, PLUS adjunctive inhaled colistin for at least 7 days. 6 Dosing should be colistin 2.5-5 mg CBA/kg/day IV in 2 or 4 divided doses with careful nephrotoxicity monitoring. 6
For bloodstream infections: Use colistin-carbapenem combination therapy, especially when carbapenem MIC ≤32 mg/L, for 10-14 days. 6 Double-covering therapy should be considered when CRAB is susceptible to more than one antibiotic, though evidence is of very low certainty. 3, 4
Extended-Spectrum Beta-Lactamase (ESBL) Producing Organisms
For healthcare-associated infections: Use carbapenem therapy such as meropenem 1g IV every 8 hours or imipenem/cilastatin 1g IV every 8 hours. 7 Add ampicillin 2g IV every 6 hours for enterococcal coverage in intra-abdominal infections. 7
For non-severe infections from low-risk sources (urinary tract, biliary after source control): Consider carbapenem-sparing alternatives like piperacillin-tazobactam to preserve carbapenems and delay resistance development. 3
Optimization Strategies
Beta-Lactam Administration
Administer β-lactams by prolonged IV infusion (3-4 hours) for severe infections, especially with high MIC pathogens. 6 Consider continuous infusion for carbapenems, ceftazidime, and piperacillin-tazobactam when risk of pharmacodynamic failure exists. 6
Therapeutic Drug Monitoring
Use optimal antibiotic dosing schemes with attention to adverse effects, particularly with polymyxins and aminoglycosides. 3 Refer to EUCAST's recommended dosing and implement therapeutic drug monitoring whenever available. 3
Source Control
Prioritize source control to optimize outcomes and shorten antibiotic treatment durations. 3 For intra-abdominal infections, perform percutaneous drainage or surgical intervention as clinically indicated. 7
Critical Pitfalls to Avoid
Never use tigecycline monotherapy for pneumonia or bloodstream infections, as it is associated with increased all-cause mortality (risk difference 0.6%, 95% CI 0.1-1.2). 6 Inadequate serum concentrations make it unsuitable for bacteremia. 7
Avoid fosfomycin monotherapy for severe systemic MDR infections outside uncomplicated UTIs. 6
Do not use polymyxin-rifampin combinations as strong evidence demonstrates lack of benefit and potential harm. 7
For polymyxin therapy, monitor for nephrotoxicity mandatorily, with polymyxin B preferred over colistin due to lower nephrotoxicity rates (adjusted HR 2.27 for colistin). 7
Obtain microbiological cultures before initiating therapy to guide targeted treatment. 4 Follow-up blood cultures for GNB bacteremia add little value unless bacteria are not sensitive to empiric antibiotics or fever persists. 8
Antimicrobial Stewardship Considerations
Reassess all antibiotic regimens at 48-72 hours and de-escalate based on clinical response and microbiological data. 6 Avoid empiric broad-spectrum antibiotics unnecessarily, as interval antibiotic therapy is the strongest risk factor for emergence of MDR bacteria (OR 5.1). 6
Implement in-ward antimicrobial stewardship programs to reduce selection pressure for resistance. 4 Use procalcitonin-guided therapy to reduce unnecessary antibiotic exposure in respiratory infections and sepsis. 4
Consult infectious disease specialists for all MDR infections to optimize treatment outcomes and reduce mortality. 6
Infection Control Measures
Implement strong hand hygiene education programs with monitoring and feedback to healthcare workers. 4 Perform active screening cultures at hospital admission for high-risk patients, followed by contact precautions. 4
Cohort patients with MDR gram-negative bacteria in designated areas and ensure proper environmental cleaning with specific disinfection protocols. 4