First-generation cephalosporins: Uses, common brands, and safety info

We’re exposed to millions of different pathogens and the risk of infectious diseases every day. It’s vital that the correct organisms are identified by healthcare providers when an infection occurs so that the proper medications can be prescribed to combat the infection quickly and effectively. Luckily when there is a bacterial infection, there are numerous antibiotic options available. Your healthcare provider will choose the most suitable antibiotic for the particular type of bacteria or certain infection they are treating. 

First-generation cephalosporins are a commonly prescribed antibiotic for when simple skin infections or common bacterial organisms are involved. They have been around the longest compared to other cephalosporin groups but are still quite effective. The chart below provides some common first-generation cephalosporins available in the United States as well as coupons and safety information.

Other first-generation cephalosporins

• Biocef (cephalexin)

• Cefadyl (cephapirin)

• Cephalothin

• Panixine (cephalexin)

• Ultracef (cefadroxil)

• Velosef (cephradine) 

What are first-generation cephalosporins?

First-generation cephalosporins are the original class of cephalosporins, which are a type of beta-lactam antibiotics. There are a total of five generations of cephalosporins that have been developed at this time. They are derived from the mold Acremonium. 

They are usually available in two forms: oral and parenteral preparations. Oral cephalosporins are usually reserved for milder, uncomplicated infections. Whereas parenteral forms are used for more serious infections as they will allow for quicker resolution of the infection. 

First-generation cephalosporins are classified as bactericidal and broad-spectrum antibiotics as they are able to kill a large variety of the bacteria they are susceptible against. Antibacterial agents listed as first-generation cephalosporins are some of the first antibiotics in their class. They are still very popular antimicrobial options even with newer generations being available on the market. These antibacterial agents are very helpful against uncomplicated gram-positive bacterial infections and are usually the antibiotic of choice for surgical prophylaxis.

How do first-generation cephalosporins work?

First-generation cephalosporins are a large group of antibiotic agents that work through their beta-lactam rings. Their pharmacokinetics involve the beta-lactam rings binding to the penicillin-binding protein that is found in various bacteria. This prevents the bacteria from completing their activities such as synthesizing the cell wall. 

Another mode of action for cephalosporins against bacteria is that they primarily work by inhibiting an enzyme called peptidoglycan that is also part of the bacterial cell wall. This also prevents cell wall synthesis in bacteria causing the bacteria to die. The pharmacology for this class of antibiotics works well in most body fluids except cerebrospinal fluid. Higher generations of cephalosporins are usually used in this location. None of the cephalosporins work well within the intracellular fluid and the vitreous humor.

Due to the popularity of first-generation cephalosporins, there is a greater risk of bacteria developing resistance to these antibiotics. Staphylococcus aureus is a common bacteria known for developing resistance to first-generation cephalosporins as this antibiotic is most commonly used to treat this particular bacteria. Staphylococcus aureus is able to develop a resistance to these types of antibiotics by modifying the gene found in the penicillin-binding protein. This change does not allow the antibiotic’s beta-lactam rings to inactivate the protein which would negatively impact the bacteria’s cell wall so that the bacteria does not die. 

Additionally, Staphylococcus aureus is able to produce an enzyme called beta-lactamase. The enzyme prevents the beta-lactam ring in cephalosporins from attaching to the penicillin-binding proteins. This type of resistant bacteria is known as methicillin-resistant Staphylococcus aureus (MRSA). Currently, only fifth-generation cephalosporins are active against MRSA. 

Cephalosporins can increase their spectrum of activity against resistant bacteria by adding beta-lactamase inhibitors to their formulas. Examples include ceftazidime-avibactam and ceftolozane-tazobactam.

Other cephalosporins

Because of potential bacterial resistance to first-generation cephalosporins, newer generations have been developed. Second-generation cephalosporins were developed to treat more gram-negative organisms, including H. influenza, Bacteroides species, Enterobacter aerogenes, Neisseria species, and Serratia marcescens. These antibiotics are divided into second-generation and the cephamycin subgroups, which include the antibiotics cefuroxime, cefprozil, cefmetazole, cefotetan, and cefoxitin. 

Third-generation cephalosporins cover H. influenza, Neisseria meningitidis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Examples of this generation of antibiotics include cefotaxime, ceftazidime, cefdinir, ceftriaxone, cefpodoxime, and cefixime. This generation can penetrate in cerebral fluid making it the ideal choice for the treatment of meningitis.

Cefepime is the only FDA-approved fourth-generation cephalosporins, which is reserved for more serious gram-positive and gram-negative bacteria. 

Ceftaroline is a fifth-generation cephalosporin, which has the most extensive bacteria coverage as it includes MRSA, Listeria monocytogenes, and Enterococcus faecalis.

What are first-generation cephalosporins used for?

Various bacterial infections can be treated with first-generation cephalosporin antibiotics. The conditions successfully treated with first-generation cephalosporins include:

• Bacterial endocarditis prevention

• Bladder infection

• Bone infection

• Gallstone inflammation

• Endocarditis

• Impetigo

• Joint infection

• Kidney infections

• Ear infection (otitis media)

• Abdominal wall inflammation

• Pharyngitis

• Pneumonia

• Prevention of birth infections associated with Group B Streptococcal disease

• Prostatitis

• Sepsis

• Skin infection

• Soft tissue infection

• Post-surgical infection prevention

• Tonsillitis

• Upper respiratory tract infection

• Urinary tract infection

First-generation cephalosporins are most effective against gram-positive bacteria such as staphylococci or streptococci. They are rarely able to adequately treat gram-negative bacteria as gram-negative organisms are usually reserved for the higher generations. The only gram-negative organisms susceptible to first-generation cephalosporins are Escherichia coli (E. coli), Proteus mirabilis, and Klebsiella pneumoniae. 

First-generation cephalosporins, although useful, have other limitations as well. These limitations include the inability to treat enterococci as well as methicillin-resistant staphylococci. 

First-generation cephalosporin antibiotics are also a great alternative for those with a penicillin allergy. They should, however, be avoided if there was a serious anaphylactic reaction that occurred with previous penicillin use.

Who can take first-generation cephalosporins?

First-generation cephalosporins are excellent antibiotic options for men, women, seniors, and children when minor bacterial infections need to be addressed. However, because seniors are prone to having less kidney function, first-generation cephalosporin antibiotics should be monitored closely to ensure kidney damage does not occur in those who are vulnerable.

Are first-generation cephalosporins safe?

The first-generation cephalosporins are considered a safe antimicrobial agent option due to their minimal toxicity with use. Most of the adverse effects associated with its use include mild gastrointestinal side effects. Because the benefits of use usually outweigh the risks, these antibiotic medications are frequently sought out by both patients and healthcare providers. 

First-generation cephalosporin restrictions

Do not use first-generation cephalosporins if you have any known:

• Hypersensitivity or allergic reactions to medication

• Anaphylactic reaction to penicillins

• Kidney disease

• History of antibiotic-associated colitis

• History of gastrointestinal disorders

• History of seizure disorder

Can you use first-generation cephalosporin antibiotics while pregnant or breastfeeding?

Research shows that first-generation cephalosporins are safe to use during pregnancy and do not cause any fetal harm. However, there are studies that show first-generation cephalosporins are able to be transmitted to infants through breast milk and may cause gastrointestinal distress to the infant. Therefore, these medications should be avoided if possible while breastfeeding.

Are first-generation cephalosporin controlled substances?

First-generation cephalosporin antibiotics are not considered controlled substances. They are not habit-forming and do not pose any risk of dependency on the medication when used to fight bacterial infections.

Common first-generation cephalosporins side effects

Side effects are common with any medication. Some commonly seen side effects to be aware of with first-generation cephalosporins include:

• Diarrhea

• Rash

• Vomiting

• Nausea

• Abdominal pain

• Decreased appetite

• Elevated liver enzymes

• Hives

• Thrombophlebitis

• Headache

• Oral thrush

• Dizziness 

• High levels of eosinophils

• Itchy skin

How much do first-generation cephalosporins cost?

Because first-generation cephalosporins have been around for some time, they are commonly used and known to be fairly affordable. This affordability makes first-generation cephalosporins a reasonable option as a first line of treatment for many Staphylococcal and Streptococcal bacterial infections. Their prices can run as low as $50 for a prescription and as high as $140. Because insurance plans have varying coverage for these types of medications, other discount programs should always be considered for cost-saving options. SingleCare has free discounts available to help lower the prices associated with first-generation cephalosporins and other prescription drugs.