Peritonitis and Abdominal Sepsis Medication

The goals of pharmacotherapy in patients with peritonitis and abdominal sepsis are to reduce morbidity and prevent complications. The agents used are antimicrobials such as cefotaxime, gentamicin, ampicillin, and sulfamethoxazole.

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Traditionally, a combination of an aminoglycoside and ampicillin was used to treat SBP. This regimen affords excellent empiric coverage of more than 90% of SBP cases caused by gram-negative aerobes or gram-positive cocci. More recently, the third-generation cephalosporin cefotaxime has been demonstrated to be as effective as the ampicillin/aminoglycoside combination, and it does not carry the increased risk of nephrotoxicity in cirrhotic patients. Cefotaxime does not cover enterococci, which are the pathogen in up to 5% of cases.

Class Summary

Cephalosporins are structurally and pharmacologically related to penicillins. They inhibit bacterial cell wall synthesis, resulting in bactericidal activity. Cephalosporins are divided into first, second, third, and fourth generation. First-generation cephalosporins have greater activity against gram-positive bacteria, and succeeding generations have increased activity against gram-negative bacteria and decreased activity against gram-positive bacteria.

Cefotaxime (Claforan)

Cefotaxime is a third-generation cephalosporin with a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Thus, it provides excellent empiric coverage of SBP.

Cefuroxime (Ceftin, Kefurox, Zinacef)

Second-generation cephalosporin; maintains gram-positive activity of first-generation cephalosporins; adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis.

Binds to penicillin binding proteins and inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Condition of patient, severity of infection, and susceptibility of microorganism determines proper dose and route of administration. Resists degradation by beta-lactamase.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; and higher efficacy against resistant organisms. Its bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins. It exerts an antimicrobial effect by interfering with synthesis of peptidoglycan, a major structural component of bacterial cell walls. Bacteria eventually lyse due to the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.

Ceftriaxone is highly stable in the presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of the dose is excreted unchanged in the urine; the remainder is secreted in bile and ultimately in feces as microbiologically inactive compounds. Ceftriaxone reversibly binds to human plasma proteins, and the binding decreases from 95% bound at plasma concentrations of less than 25 mcg/mL to 85% bound at 300 mcg/mL.

Cefotetan

Cefotetan is a second-generation cephalosporin used as single-drug therapy to provide broad gram-negative coverage and anaerobic coverage. Also provides some coverage of gram-positive bacteria. Half-life is 3.5 h. Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death.

Cefepime

Cefepime is a fourth-generation cephalosporin. Gram-negative coverage comparable to ceftazidime but has better gram-positive coverage (comparable to ceftriaxone). Cefepime is a zwitter ion; rapidly penetrates gram-negative cells. Best beta-lactam for IM administration.

Class Summary

Aminoglycosides are bactericidal antibiotics used primarily to treat gram-negative infections. They interfere with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.

Gentamicin (Gentacidin, Garamycin)

Gentamicin is an aminoglycoside antibiotic effective against Pseudomonas aeruginosa; E coli; and Proteus, Klebsiella, and Staphylococcus species. Gentamicin is also variably effective against some strains of certain gram-positive organisms, including S aureus, enterococci, and L monocytogenes. Dosing regimens are numerous; adjust the dose based on creatinine clearance and changes in volume of distribution. Gentamicin may be given IV/IM. Gentamicin has been reported to offer additive or synergistic activity against enterococci when used with ampicillin.

Class Summary

The penicillins are bactericidal antibiotics that work against sensitive organisms at adequate concentrations and inhibit the biosynthesis of cell wall mucopeptide.

Piperacillin and Tazobactam sodium (Zosyn)

Piperacillin is a semisynthetic extended-spectrum penicillin that inhibits bacterial cell wall synthesis by binding to specific penicillin-binding proteins; it is the most effective of the antipseudomonal penicillins.

Tazobactam increases piperacillin activity against S aureus, Klebsiella, Enterobacter, and Serratia species; the greatest increase is in activity against B fragilis. However, it does not increase anti–P aeruginosa activity.

Amoxicillin and clavulanate (Augmentin)

Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins; clavulanate inhibits beta-lactamase producing bacteria. This combination is a good alternative antibiotic for patients allergic or intolerant to the macrolide class. Usually, it is well tolerated, and it provides good coverage to most infectious agents. It is not effective against Mycoplasma and Legionella species. The half-life of the oral dosage form is 1-1.3 hours. It has good tissue penetration but does not enter cerebrospinal fluid.

Ticarcillin and clavulanate potassium (Ticar)

This combination of an antipseudomonal penicillin with a beta-lactamase inhibitor provides coverage against most gram-positive and gram-negative organisms, as well as most anaerobes. It inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active growth.

Ampicillin (Omnipen, Marcillin)

Ampicillin interferes with bacterial cell wall synthesis during active multiplication, causing bactericidal activity against susceptible organisms. Dose adjustments may be necessary in renal failure. Rash should be evaluated carefully to differentiate nonallergic ampicillin rash from hypersensitivity reaction.

Class Summary

Macrolide antibiotics have bacteriostatic activity and exert their antibacterial action by binding to the 50S ribosomal subunit of susceptible organisms, resulting in inhibition of protein synthesis

Tobramycin (Nebcin)

Tobramycin is used in skin, bone, and skin structure infections, caused by S aureus, P aeruginosa, Proteus species, E coli, Klebsiella species, and Enterobacter species. It is indicated in the treatment of staphylococcal infections when penicillin or potentially less-toxic drugs are contraindicated and when bacterial susceptibility and clinical judgment justifies its use. Like other aminoglycosides, tobramycin is associated with nephrotoxicity and ototoxicity.

Clindamycin (Cleocin)

Clindamycin is a semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of its parent compound lincomycin. It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Clindamycin distributes widely in the body without penetration of the CNS. Clindamycin is protein bound and excreted by the liver and kidneys.

Class Summary

Carbapenems are structurally related to penicillins and have broad-spectrum bactericidal activity. The carbapenems exert their effect by inhibiting cell wall synthesis, which leads to cell death. They are active against gram-negative bacteria, gram-bacteria, and anaerobes.

Meropenem (Merrem IV)

A bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis, meropenem is effective against most gram-positive and gram-negative bacteria. Compared with imipenem, meropenem has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci.

Aztreonam (Azactam)

Aztreonam is a monobactam, not a beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. It is active against gram-negative bacilli but has very limited gram-positive activity and is not useful for anaerobes. Aztreonam lacks cross-sensitivity with beta-lactam antibiotics. It may be used in patients allergic to penicillins or cephalosporins. Transient or persistent renal insufficiency may prolong serum levels.

Ertapenem (Invanz)

The bactericidal activity of ertapenem results from inhibition of cell wall synthesis and is mediated through binding to penicillin-binding proteins. Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended spectrum beta-lactamases; it is hydrolyzed by metallo-beta-lactamases.

Imipenem and cilastatin (Primaxin)

This combination is used for treatment of infections with multiple organisms because other agents do not have wide spectrum coverage or are contraindicated due to potential for toxicity.

Class Summary

Fluoroquinolones have broad-spectrum activity against gram-positive and gram-negative aerobic organisms. They inhibit DNA synthesis and growth by inhibiting DNA gyrase and topoisomerase, which is required for replication, transcription, and translation of genetic material.

Ciprofloxacin (Cipro)

Ciprofloxacin, a fluoroquinolone, inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerase, which is required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. It has no activity against anaerobes. Continue treatment for at least 2 days (7-14 d typical) after signs and symptoms have disappeared. In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust the dose in the presence of renal function impairment. Superinfections may occur with prolonged or repeated antibiotic therapy.

Norfloxacin (Chibroxin, Noroxin)

Norfloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms, but it has no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, growth.

Class Summary

Anti-infectives such as metronidazole and sulfamethoxazole/trimethoprim are effective against some types of bacteria that have become resistant to other antibiotics.

Sulfamethoxazole and trimethoprim (Bactrim, Bactrim DS, Cotrim, Cotrim DS, Septra, Septra DS)

Trimethoprim-sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. Its antibacterial activity includes common urinary tract pathogens, except Pseudomonas aeruginosa.

Metronidazole (Flagyl)

Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents (but is used as monotherapy in C difficile enterocolitis).

Class Summary

Glycylcycline antibiotics are structurally similar to tetracycline antibiotics and were developed to overcome bacterial mechanisms of tetracycline resistance. Tigecycline is the first drug approved in this class.

Tigecycline (Tygacil)

Tigecycline is a glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. It is used for complicated intra-abdominal infections caused by C freundii, E cloacae, E coli, K oxytoca, K pneumoniae, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible isolates only), S anginosus group. (includes S anginosus, S intermedius, and S constellatus), B fragilis, B thetaiotaomicron, B uniformis, B vulgatus, C perfringens, and P micros. Use with caution in patients with severe hepatic impairment.