Other cephalosporins

Definition and Classification Context
The term “other cephalosporins” refers to beta-lactam antibiotics that belong to the broader cephalosporin class but do not fall strictly into the traditional generational classification (first to fifth generation) or are part of specialized subgroups such as cephalosporin derivatives, side-chain-modified agents, or orphan cephalosporins developed for specific bacterial targets. These agents may feature unique antimicrobial spectra, beta-lactamase resistance profiles, or route-specific utility (e.g., ophthalmic or intramuscular-only products).

This group includes older cephalosporins not commonly in use today, newly engineered cephalosporins with advanced beta-lactamase stability, and combination agents that are not easily classified within a standard generation.

---

1. Mechanism of Action

All cephalosporins—including those in this “other” category—function by:

• Inhibiting bacterial cell wall synthesis

• Binding to penicillin-binding proteins (PBPs)

• Blocking peptidoglycan cross-linking

• Causing bacterial cell lysis and death (bactericidal)

These agents are structurally similar to penicillins but with a six-membered dihydrothiazine ring fused to the beta-lactam ring (vs. a five-membered thiazolidine in penicillins), conferring different resistance profiles and spectrum of activity.

---

2. Unique Features of 'Other Cephalosporins'

• May include older cephalosporins not widely prescribed today

• Often administered via IM injection, topical, or ophthalmic routes

• May be non-generational, i.e., they do not fit standard 1st–5th generation classification

• Some are used for niche infections or in resource-limited settings

• Others serve as intermediates between generations in terms of spectrum

---

3. Representative Agents

Generic Name	Brand Name(s)	Use	Notes
Cefacetrile	–	Bovine mastitis (veterinary use)	Not used in humans
Cefazaflur	–	Gram-positive coverage	Rarely used in modern therapy
Cefaclor monohydrate	Ceclor, Distaclor	RTIs, UTIs, otitis media	Variant of 2nd-gen cephalosporin
Cefatrizine	–	Broad-spectrum oral use	Rarely available today
Cefapirin	–	Early-generation cephalosporin	Formerly used for mastitis (vet/human)
Cefonicid	Monocid	Skin, soft tissue infections	Longer half-life than cefazolin
Ceforanide	–	Gram-negative and positive cocci	Discontinued in many regions
Ceftezole	–	Surgical prophylaxis	Limited use; similar to cefazolin
Cefroxadine	Roxil	Similar to cefadroxil	Oral; low usage globally
Cefalonium	–	Veterinary cephalosporin	Not for human use
Cefmenoxime	Cefmax	Broad Gram-negative activity	Similar to 3rd-gen agents
Cefpirome	Cefrom	Nosocomial infections	4th-gen-like; more common in EU/Asia
Cefmetazole	Zefazone	Anaerobes, Gram-negative bacilli	Cephamycin subgroup (cefoxitin-like)
Cefotiam	Pansporin	Broad-spectrum cephalosporin	Popular in Japan, Korea
Cefbuperazone	–	Broad activity including Pseudomonas	Used primarily in Japan

4. Spectrum of Activity

These agents exhibit variable activity across Gram-positive, Gram-negative, and anaerobic bacteria. For example:

• Cefmetazole, a cephamycin, exhibits notable anaerobic activity

• Cefpirome resembles 4th-generation agents with extended Gram-negative coverage

• Cefonicid and cefotiam possess enhanced Gram-positive potency

In general, “other cephalosporins” often fill gaps where resistance to mainstream agents is emerging, particularly in hospital-acquired infections or in countries where their use is well established but not globalized.

---

5. Therapeutic Indications

Indication	Applicable Agents
Respiratory tract infections	Cefroxadine, Cefotiam
Surgical prophylaxis	Ceftezole, Cefonicid
Skin and soft tissue infections	Cefbuperazone, Cefmenoxime
Urinary tract infections	Cefmetazole, Ceforanide
Nosocomial infections including Pseudomonas	Cefpirome, Cefbuperazone
Infections in penicillin-allergic patients*	Depends on cross-reactivity; caution advised

6. Routes of Administration

Route	Agents
Oral	Cefatrizine, Cefroxadine, Cefaclor monohydrate
Intramuscular/IV	Cefmenoxime, Cefpirome, Cefmetazole, Cefotiam
Topical/Ophthalmic	Cefazaflur (rare), cefapirin (some veterinary use)

7. Adverse Effects

As with all cephalosporins:

System	Reactions
GI	Diarrhea, nausea, C. difficile–associated colitis
Hypersensitivity	Rash, urticaria, cross-reactivity in penicillin-allergic pts
Hematologic	Eosinophilia, thrombocytopenia (rare)
Hepatic	Transaminase elevation
Renal	Interstitial nephritis (rare), especially with high doses

Some agents like cefmetazole may cause hypoprothrombinemia or disulfiram-like reactions due to N-methylthiotetrazole (MTT) side chains.

---

8. Contraindications

• History of anaphylaxis to cephalosporins or penicillins

• Severe renal impairment (dose adjustments required)

• Hypersensitivity to beta-lactam ring structures

• Avoid alcohol with MTT side-chain agents (e.g., cefmetazole)

---

9. Precautions and Monitoring

Parameter	Monitoring Guidance
Renal function	Adjust dose for CrCl <30 mL/min
CBC	Watch for eosinophilia, leukopenia with prolonged use
Liver enzymes	Monitor ALT/AST if therapy exceeds 7–10 days
INR/PT	Especially with MTT-containing drugs
Superinfection	Monitor for signs of fungal/Clostridium overgrowth

10. Drug Interactions

Interacting Drug	Effect
Anticoagulants (warfarin)	↑ INR with cefmetazole, cefotetan (MTT side chain)
Aminoglycosides	↑ Nephrotoxicity potential
Loop diuretics	Additive renal risk
Alcohol	Disulfiram-like reactions with MTT-containing cephalosporins
Probenecid	Inhibits renal excretion; ↑ cephalosporin levels

11. Clinical Pearls

• Cefmetazole and related agents resemble cephamycins, and thus are effective against anaerobes and beta-lactamase producers

• Cefpirome is 4th-gen equivalent, though not widely approved in the U.S.; active against Pseudomonas

• Cefonicid offers once-daily dosing due to its long half-life

• Many “other cephalosporins” are regionally important, especially in Asia and Europe

• Some agents are obsolete or discontinued in high-income countries but used in resource-limited settings

---

12. Resistance Considerations

While many agents in this group retain activity against common pathogens, resistance is emerging:

• Beta-lactamase–producing organisms (e.g., ESBLs) reduce efficacy in many older cephalosporins

• PBP mutations (as in MRSA, PRSP) limit cephalosporin utility

• Anaerobic resistance is variable; cephamycins help bridge this gap

---

13. Special Populations

Population	Considerations
Pregnancy	Most agents are Category B (safe); limited data for some
Pediatrics	Dose adjustments required by weight and age
Elderly	Risk of renal impairment; monitor creatinine clearance
Renal Impairment	Dose reduction mandatory for IV agents like cefmenoxime

14. Summary Table: Selected 'Other Cephalosporins'

Drug	Spectrum	Route	Notable Uses
Cefmetazole	Gram-neg, anaerobes	IV/IM	Intra-abdominal infections
Cefpirome	Broad incl. Pseudomonas	IV	Nosocomial infections
Cefotiam	Broad Gram-positive	IV/IM	SSTIs, respiratory infections
Cefonicid	Gram-positive	IV/IM	Prophylaxis, SSTIs
Cefbuperazone	Broad, Pseudomonas	IV	Hospital-acquired infections
Cefaclor monohydrate	RTIs	Oral	URTIs, otitis media