Beta-lactam antibiotic
-lactam antibiotics are a broad class of antibiotics which include penicillin derivatives, cephalosporins, monobactams, carbapenems and -lactamase inhibitors; basically any antibiotic agent which contains a -lactam nucleus in its molecular structure. They are the most widely used group of antibiotics available.

# Clinical use
-lactam antibiotics are indicated for the prophylaxis and treatment of bacterial infections caused by susceptible organisms. While traditionally -lactam antibiotics were mainly active only against Gram-positive bacteria, the development of broad-spectrum -lactam antibiotics active against various Gram-negative organisms has increased their usefulness.

# Mode of action
-Lactam antibiotics are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls.  The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs).
-lactam antibiotics are analogues of D-alanyl-D-alanine - the terminal amino acid residues on the precursor NAM/NAG-peptide subunits of the nascent peptidoglycan layer. The structural similarity between -lactam antibiotics and D-alanyl-D-alanine facilitates their binding to the active site of penicillin binding proteins (PBPs). The -lactam nucleus of the molecule irreversibly binds to (acylates) the Ser403 residue of the PBP active site. This irreversible inhibition of the PBPs prevents the final crosslinking (transpeptidation) of the nascent peptidoglycan layer, disrupting cell wall synthesis.
Under normal circumstances peptidoglycan precursors signal a reorganisation of the bacterial cell wall and consequently trigger the activation of autolytic cell wall hydrolyses. Inhibition of cross-linkage by -lactams causes a build-up of peptidoglycan precurors which triggers the digestion of existing peptidoglycan by autolytic hydrolases without the production of new peptidoglycan. This as a result further enhances the bactericidal action of -lactam antibiotics.

# Modes of resistance
By definition, all -lactam antibiotics have a -lactam ring in their structure.  The effectiveness of these antibiotics relies on their ability to reach the PBP intact and their ability to bind to the PBP.  Hence, there are 2 main modes of bacterial resistance to -lactams, as discussed below.
The first mode of -lactam resistance is due to enzymatic hydrolysis of the -lactam ring. If the bacteria produces the enzymes -lactamase or penicillinase, these enzymes will break open the -lactam ring of the antibiotic, rendering the antibiotic ineffective.  The genes encoding these enzymes may be inherently present on the bacterial chromosome or may be acquired via plasmid transfer, and beta-lactamase gene expression may be induced by exposure to beta-lactams.  The production of a -lactamase by a bacterium does not necessarily rule out all treatment options with -lactam antibiotics.  In some instances, -lactam antibiotics may be co-administered with a -lactamase inhibitor.
However, in all cases where infection with -lactamase-producing bacteria is suspected, the choice of a suitable -lactam antibiotic should be carefully considered prior to treatment.  In particular, choosing appropriate -lactam antibiotic therapy is highly important against organisms with inducible -lactamase expression.  If -lactamase production is inducible, then failure to use the most appropriate -lactam antibiotic therapy at the onset of treatment will result in induction of -lactamase production, thereby making further efforts with other -lactam antibiotics more difficult.
The second mode of -lactam resistance is due to possession of altered penicillin binding proteins.  -lactams cannot bind as effectively to these altered PBPs, and as a result, the -lactams are less effective at disrupting cell wall synthesis.  Notable examples of this mode of resistance include methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae.  Altered PBPs do not necessarily rule out all treatment options with -lactam antibiotics.

# Common -lactam antibiotics

## Penicillins
Main article: penicillin

### Narrow spectrum penicillins
- benzathine penicillin
- benzylpenicillin (penicillin G)
- phenoxymethylpenicillin (penicillin V)
- procaine penicillin

### Narrow spectrum penicillinase-resistant penicillins
- methicillin
- dicloxacillin
- flucloxacillin

### Narrow spectrum -lactamase-resistant penicillins
- temocillin

### Moderate spectrum penicillins
- amoxicillin
- ampicillin

### Broad spectrum penicillins
- co-amoxiclav (amoxicillin+clavulanic acid)

### Extended Spectrum Penicillins
- azlocillin
- carbenicillin
- ticarcillin
- mezlocillin
- piperacillin

## Cephalosporins
Main article: cephalosporin

### First generation cephalosporins
Moderate spectrum.
- cefalexin
- cephalothin
- cefazolin

### Second generation cephalosporins
Moderate spectrum with anti-Haemophilus activity.
- cefaclor
- cefuroxime
- cefamandole

### Second generation cephamycins
Moderate spectrum with anti-anaerobic activity.
- cefotetan
- cefoxitin

### Third generation cephalosporins
Broad spectrum.
- ceftriaxone
- cefotaxime
- cefpodoxime
Broad spectrum with anti-Pseudomonas activity.
- ceftazidime

### Fourth generation cephalosporins
Broad spectrum with enhanced activity against Gram positive bacteria and beta-lactamase stability.
- cefepime
- cefpirome

## Carbapenems
Main article: carbapenem
Broadest spectrum of beta-lactam antibiotics.
- imipenem (with cilastatin)
- meropenem
- ertapenem
- faropenem

## Monobactams
Unlike other beta-lactams, there is no fused ring attached to beta-lactam nucleus.  Thus, there is less probability of cross-sensitivity reactions.
- aztreonam (Azactam)

## Beta-lactamase inhibitors
Negligible antimicrobial activity although they contain the beta-lactam ring.  Their sole purpose is to prevent the inactivation of beta-lactam antibiotics by binding the beta-lactamases, and as such, they are co-administered with beta-lactam antibiotics.
- clavulanic acid
- tazobactam
- sulbactam

# Adverse effects

## Adverse drug reactions
Common adverse drug reactions (ADRs) for the -lactam antibiotics include: diarrhea, nausea, rash, urticaria, superinfection (including candidiasis). (Rossi, 2004)
Infrequent ADRs include: fever, vomiting, erythema, dermatitis, angioedema, pseudomembranous colitis. (Rossi, 2004)
Pain and inflammation at the injection site is also common for parenterally-administered -lactam antibiotics.

## Allergy/hypersensitivity
Allergic reactions to any -lactam antibiotic may occur in up to 10% of patients receiving that agent. Anaphylaxis will occur in approximately 0.01% of patients. (Rossi, 2004) There is perhaps a 5-10% cross-sensitivity between penicillin-derivatives, cephalosporins and carbapenems; but this figure has been challenged by various investigators.
Nevertheless, the risk of cross-reactivity is sufficient to warrant the contraindication of all -lactam antibiotics in patients with a history of severe allergic reactions (urticaria, anaphylaxis, interstitial nephritis) to any -lactam antibiotic.