What are the treatment options for bacterial infections using cephalsporins (cephalosporins)?

Cephalosporin Treatment Options for Bacterial Infections

Cephalosporins are broad-spectrum bactericidal antibiotics with distinct generations offering different coverage patterns: first-generation agents (cefazolin) excel against staphylococci and streptococci, second-generation agents provide enhanced gram-negative coverage, and third-generation agents (ceftriaxone, cefotaxime, ceftazidime) offer superior activity against Enterobacteriaceae and select resistant organisms, though their extended use should be restricted to prevent resistance emergence, particularly ESBL-producing bacteria. 1

Generation-Specific Coverage and Clinical Applications

First-Generation Cephalosporins

• Cefazolin is the preferred first-generation agent with optimal activity against methicillin-sensitive Staphylococcus aureus (MSSA) and streptococci 1, 2
• Indicated for skin and soft tissue infections including impetigo, non-purulent cellulitis, and surgical site infections away from the axilla or perineum 1
• FDA-approved for respiratory tract infections (S. pneumoniae, S. aureus, S. pyogenes), urinary tract infections (E. coli, P. mirabilis), bone and joint infections, and septicemia 2
• Perioperative prophylaxis: Cefazolin is the standard for contaminated or potentially contaminated procedures (vaginal hysterectomy, cholecystectomy, open-heart surgery, prosthetic arthroplasty), typically discontinued within 24 hours post-procedure, though may continue 3-5 days for high-risk surgeries 2
• First-generation agents demonstrate limited activity against gram-negative bacilli beyond E. coli, Klebsiella, and P. mirabilis 3, 4

Second-Generation Cephalosporins

• Cefuroxime and cefoxitin provide enhanced coverage against Haemophilus influenzae compared to first-generation agents 3
• Recommended for animal bites (cefuroxime, cefoxitin) in combination regimens and moderate intra-abdominal infections 1
• Cefoxitin offers anaerobic coverage including some Bacteroides species 1

Third-Generation Cephalosporins

Ceftriaxone and cefotaxime are the cornerstone third-generation agents with critical clinical applications:

• Bacterial meningitis: Third-generation cephalosporins (except cefoperazone) penetrate cerebrospinal fluid and are drugs of choice for H. influenzae type b meningitis and pneumococcal/meningococcal meningitis caused by penicillin-resistant strains 1
• Superior to chloramphenicol and second-generation cephalosporins for childhood bacterial meningitis 1
• For highly penicillin- and cephalosporin-resistant pneumococcal meningitis, combine vancomycin with third-generation cephalosporin (never vancomycin alone) 1

Intra-abdominal infections:

• Ceftriaxone or cefotaxime plus metronidazole are first-line for severe community-acquired intra-abdominal infections 1
• For mild-to-moderate infections, combination therapy with ceftriaxone/cefotaxime plus metronidazole provides adequate coverage 1
• Plasma and peritoneal concentrations of cefotaxime are similar, requiring no dose adjustment in severe intra-abdominal infections 1

Ceftazidime and cefepime:

• Ceftazidime provides antipseudomonal coverage and is reserved for Pseudomonas aeruginosa infections 1, 5
• Cefepime (fourth-generation) offers broader spectrum than third-generation agents with activity against AmpC-producing organisms, but requires metronidazole for anaerobic coverage 1
• Increased doses of ceftazidime required for adequate peritoneal concentrations in severe intra-abdominal infections 1

Skin and soft tissue infections:

• Necrotizing fasciitis: Ceftriaxone plus metronidazole (with vancomycin or linezolid for broader coverage) 1
• Diabetic wound infections (moderate-to-severe): Ceftriaxone as part of combination regimens 1

Critical Resistance and Stewardship Considerations

ESBL-Producing Enterobacteriaceae

In settings with high ESBL prevalence, extended cephalosporin use must be discouraged and limited to pathogen-directed therapy due to selective pressure driving resistance emergence. 1

• Overuse of cephalosporins has directly contributed to increasing ESBL-producing Enterobacteriaceae and MRSA prevalence 1
• Treatment failure occurs with cephalosporins or piperacillin-tazobactam against ESBL producers even when appearing susceptible in vitro; carbapenems are preferred 1

Novel Beta-Lactamase Inhibitor Combinations

• Ceftolozane/tazobactam: Strong activity against ESBL-producing Enterobacteriaceae and multiresistant Pseudomonas, must be combined with metronidazole for intra-abdominal infections 1
• Ceftazidime/avibactam: Consistent activity against Klebsiella pneumoniae carbapenemase (KPC) producers, requires metronidazole for anaerobic coverage 1
• These agents preserve carbapenems for treating gram-negative multidrug-resistant organisms, though cautious use advised until roles better defined 1

Antimicrobial De-escalation

• Reassess patients when microbiological results available and de-escalate therapy when appropriate 1
• De-escalation associated with lower ICU mortality rates and is key antimicrobial stewardship practice 1
• MDR non-fermenting gram-negative organisms limit de-escalation implementation 1

Pharmacokinetic Advantages

• Ceftriaxone: Long half-life permits once-daily dosing, making it excellent for outpatient parenteral antibiotic therapy and treatment of Lyme disease and sexually transmitted diseases 5
• Meropenem (carbapenem alternative): Broad activity with less seizure risk than imipenem, equivalent outcomes to cefotaxime/ceftriaxone for bacterial meningitis 1

Common Pitfalls and Contraindications

• Never use cephalosporins for enterococcal infections—they lack activity and superinfection with enterococci has occurred during treatment 4
• Avoid imipenem for meningitis due to 33% seizure risk in children 1
• Cephalosporins ineffective against MRSA; use vancomycin, linezolid, or daptomycin instead 1
• Bacteroides fragilis and Pseudomonas aeruginosa treatment unsatisfactory with many cephalosporins; use specific agents (ceftazidime for Pseudomonas, metronidazole for Bacteroides) 4
• Dose adjustment required in renal impairment to prevent seizures from inappropriately high levels 2
• Monitor prothrombin time in patients with renal/hepatic impairment, poor nutritional state, or on anticoagulants due to potential fall in prothrombin activity 2