Medication Summary
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 spontaneous bacterial peritonitis (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.
Cephalosporins
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.
Aminoglycosides
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.
Penicillins
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 provides good coverage for 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.
Macrolides
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 is excreted by the liver and kidneys.
Carbapenems
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.
Imipenem/cilastatin/relebactam (Recarbrio)
Three-drug combination containing previously approved imipenem/cilastatin and relebactam, a beta-lactamase inhibitor. It is indicated for complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections in adults with limited or no other treatment options. Dosage modifications are necessary for patients who have renal impairment.
Fluoroquinolones
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.
Glycylcycline Antibiotic
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.
Tetracyclines
Class Summary
Eravacycline is a synthetic fluorocycline antibiotic belonging the tetracycline drug class. Approval for complicated intra-abdominal infections was based on results from the IGNITE-1 clinical trial (n=541) which demonstrated eravacycline to be noninferior to ertapenem. [35]
Eravacycline (Xerava)
Fluorocycline antibacterial within the tetracycline class; disrupts bacterial protein synthesis by binding the 30S ribosomal subunit, thus preventing incorporation of amino acid residues into elongating peptide chains. It is indicated for treatment of complicated intra-abdominal infections caused by the following susceptible bacteria: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Klebsiella oxytoca, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus anginosus group, Clostridium perfringens, Bacteroides species, or Parabacteroides distasonis.
Anti-Infectives
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).
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Peritonitis and abdominal sepsis. Diagnostic and therapeutic approach to peritonitis and peritoneal abscess.
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Peritonitis and abdominal sepsis. A 48-year-old man underwent suprapubic laparotomy, right hemicolectomy, and gastroduodenal resection for right colon cancer invading the first portion of the duodenum. After surgery, the patient developed abdominal pain and distention. Computed tomography (CT) scanning was used to confirm an anastomotic dehiscence. Figure A shows a contrast-enhanced scan of the abdomen and pelvis that reveals multiple fluid collections, perihepatic ascites, and mild periportal edema. A collection of fluid containing an air-fluid level is visible anterior to the left lobe of the liver. A second collection is anterior to the splenic flexure of the colon. In figure B, a third fluid collection is present in the inferior aspect of the lesser space and in the transverse mesocolon. Figure C shows the pelvis with a collection of free fluid in the rectovesical pouch.
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Peritonitis and abdominal sepsis. A 78-year-old man was admitted with a history of prior surgery for small bowel obstruction and worsening abdominal pain, distended abdomen, nausea, and obstipation. In figure A, a marked amount of portal venous gas within the liver, mesenteric venous gas, and pneumatosis intestinalis are consistent with ischemic small intestine. The superior mesenteric artery appears patent. The liver has a nodular contour consistent with cirrhosis. In figures B and C, markedly distended loops of small intestine containing fluid and air-fluid levels are consistent with a small bowel obstruction. No focal fluid collections are identified.
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Peritonitis and abdominal sepsis. A 35-year-old man with a history of Crohn disease presented with pain and swelling in the right abdomen. In figure A, a thickened loop of terminal ileum is evident adherent to the right anterior abdominal wall. In figure B, the right anterior abdominal wall is markedly thickened and edematous, with adjacent inflamed terminal ileum. In figure C, a right lower quadrant abdominal wall abscess and enteric fistula are observed and confirmed by the presence of enteral contrast in the abdominal wall.
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Peritonitis and abdominal sepsis. Gram-negative Escherichia coli.
Tables
Source Regions |
Causes |
Esophagus |
Boerhaave syndrome Malignancy Trauma (mostly penetrating) Iatrogenic* |
Stomach |
Peptic ulcer perforation Malignancy (eg, adenocarcinoma, lymphoma, gastrointestinal stromal tumor) Trauma (mostly penetrating) Iatrogenic* |
Duodenum |
Peptic ulcer perforation Trauma (blunt and penetrating) Iatrogenic* |
Biliary tract |
Cholecystitis Stone perforation from gallbladder (ie, gallstone ileus) or common duct Malignancy Choledochal cyst (rare) Trauma (mostly penetrating) Iatrogenic* |
Pancreas |
Pancreatitis (eg, alcohol, drugs, gallstones) Trauma (blunt and penetrating) Iatrogenic* |
Small bowel |
Ischemic bowel Incarcerated hernia (internal and external) Closed loop obstruction Crohn disease Malignancy (rare) Meckel diverticulum Trauma (mostly penetrating) |
Large bowel and appendix |
Ischemic bowel Diverticulitis Malignancy Ulcerative colitis and Crohn disease Appendicitis Colonic volvulus Trauma (mostly penetrating) Iatrogenic |
Uterus, salpinx, and ovaries |
Pelvic inflammatory disease (eg, salpingo-oophoritis, tubo-ovarian abscess, ovarian cyst) Malignancy (rare) Trauma (uncommon) |
*Iatrogenic trauma to the upper GI tract, including the pancreas and biliary tract and colon, often results from endoscopic procedures; anastomotic dehiscence and inadvertent bowel injury (eg, mechanical, thermal) are common causes of leak in the postoperative period. |
|
Type |
Organism |
Percentage |
Aerobic |
|
|
Gram negative |
Escherichia coli |
60% |
|
Enterobacter/Klebsiella |
26% |
|
Proteus |
22% |
|
Pseudomonas |
8% |
Gram positive |
Streptococci |
28% |
|
Enterococci |
17% |
|
Staphylococci |
7% |
Anaerobic |
Bacteroides |
72% |
|
Eubacteria |
24% |
|
Clostridia |
17% |
|
Peptostreptococci |
14% |
|
Peptococci |
11% |
Fungi |
Candida |
2% |
Peritonitis (Type) |
Etiologic Organisms |
Antibiotic Therapy (Suggested) |
|
Class |
Type of Organism |
||
Primary |
Gram-negative |
E coli (40%) K pneumoniae (7%) Pseudomonas species (5%) Proteus species (5%) Streptococcus species (15%) Staphylococcus species (3%) Anaerobic species (< 5%) |
Third-generation cephalosporin |
Secondary |
Gram-negative |
E coli Enterobacter species Klebsiella species Proteus species |
Second-generation cephalosporin Third-generation cephalosporin Penicillins with anaerobic activity Quinolones with anaerobic activity Quinolone and metronidazole Aminoglycoside and metronidazole |
Gram-positive |
Streptococcus species Enterococcus species |
||
Anaerobic |
Bacteroides fragilis Other Bacteroides species Eubacterium species Clostridium species Anaerobic Streptococcus species |
||
Tertiary |
Gram-negative |
Enterobacter species Pseudomonas species Enterococcus species |
Second-generation cephalosporin Third-generation cephalosporin Penicillins with anaerobic activity Quinolones with anaerobic activity Quinolone and metronidazole Aminoglycoside and metronidazole Carbapenems Triazoles or amphotericin (considered in fungal etiology) (Alter therapy based on culture results.) |
Gram-positive |
Staphylococcus species |
||
Fungal |
Candida species |
||
Routine |
Optional |
Unusual |
Less Helpful |
Cell count |
Obtain culture in blood culture (BC) bottles. |
Tuberculosis (TB) smear and culture |
pH |
Albumin |
Glucose |
Cytology |
Lactate |
Total protein |
Lactate dehydrogenase (LDH) |
Triglyceride |
Cholesterol |
|
Amylase |
Bilirubin |
Fibronectin |
|
Gram stain |
|
Alpha 1-antitrypsin |
|
|
|
Glycosaminoglycans |
