ročník 11,2003 č.4
Satelites

Cefoperazon in biliary tract infections - experience from multicenter clinical observation

Procházka V., Šváb J., Kolář M.

2nd Clinic of Internal Medicine, Faculty Hospital Olomouc
1st Surgical Clinic, 1. Medical Faculty, Charles University and Vinohradská Faculty Hospital Prague
Department of Microbiology

Preconditions

An indispensible part of the treatment of biliary tract infections is the administration of a suitable antibiotic. Goal-directed therapy at the beginning of the illness is not possible. Therefore, it is necessary to initiate treatment empirically according to the principles of initial antibiotherapy (1). Among suitable antibiotics are ß-lactam antibiotics (piperacilin, aminopenicilins combined with inhibitors of bacterial ß- lactamases), cephalosporins of the 2nd and 3rd generation (possibly in combination with aminoglycosides or metronidazol) and fluorochinolons (1, 2).
In illnesses without obstructions of the biliary tract, antibiotics penetrate the bile relatively well (3). During complete obstruction of the biliary duct, only cephalosporin of the 3rd generation-cefoperazon, is noted as having good penetration into the bile (4). The concentrations of cefoperazon in the bile and in tissues of the gallbladder are higher than of other cephalosporins and reach up to a hundred times those of serum concentrations (5, 6). Cefoperazon proved its worth in the treatment of biliary tract infections in the surgically ill (4, 7, 8). The dual method of excretion ensures safe administration even during light or moderate dysfunctions of the kidneys or liver (5).

Study aims

The main aim of the prospective multicentric study was the evaluation of treatment of biliary tract infections with cefoperazon. The administration method, clinical efficiency and mortality of the patients were studied. Concurrently, microbial examination, evaluation of bacterial effectiveness and influence of risk factors on the course of therapy were determined.

Methods

Cefoperazon, as the antibiotic of choice, was administered to patients standardly treated for acute cholecystitis, cholangitis even with simultaneous acute pancreatitis, liver abscess, or intra-abdominal infection. The patients were followed prospectively according to to a uniform protocol. Observation and data collection took place at Intensive Care Units and Standard Surgical Units and Internal Units in the Czech Republic. Microbiological examination included determining the bacterial etiologic agent and evaluating its elimination or persistence. The protocols were processed by an independent statistical subject.

Results

212 patient protocols were evaluated from 30 workplaces (Tab.1).

Surgery
Internal Medicine
Surgical Intensive Care Unit
Internal Intensive Care Unit
58.5 %
12.3 %
23.1 %
6.1 %
Total 30
Tab. No.1 - Specialty representation of workplaces

The average age was 61 years, the women outnumbered the men (54.2%). The dividing of patients according to diagnosis is shown in Table 2.

Acute cholecystitis
Cholangitis
Acute pankreatitis
Liver abscess
Intra-abdominal infection
37.3 %
38.2 %
15.1 %
3.3 %
6.1 %
Total 212
Tab. No.2 - Division according to diagnosis

Cefoperazon was administered in the initial treatment to 86.8%, as a second choice drug in 13.2% (Tab.3).

In intial treatment
As drug of second choice
86.8 %
13.2 %
Tab. No.3 - Cefoperazon indicated

Most often, dose of 2g was administered intravenously every 12 hours for a period of 7 days. Sufficient clinical efficiency was observed in 90% (Tab.4).

Diagnosis acute cholecystitis cholangitis pancreatitis liver abscess
Effective
Ineffective
98,7%
1,3%
88,9%
11,2%
71,9%
28,1
85,7%
14,3%
Tab. No.4 - Clinical effectiveness of cefoperazon

Efficiency was lowest (72%) in patients with simultaneously occuring acute pancreatitis.
High effectivity was noted in the treatment of acute cholecystitis (99%) and in the treatment of acute cholangitis (89%). A bacterial etiologic agent was determined in 22% of those treated whereas enterobacteria prevailed. Elimination of the original microbial infect was verified in 91.3% of the evaluated patients (Tab.5).

Clinical efficiency
Bacteriological efficiency
90 %
91 %
Tab. No.5 - Total effectiveness of cefoperazon treatment

Total mortality reached 3.3%. The highest mortality was seen in patients with liver abscesses (14.3%). In the group of those treated for acute pancreatitis, two patients died (6.3%). The mortality of patients with acute cholangitis was 3.7%. No patients with acute cholecystitis died (Tab.6).

Total
Acute cholecystitis
Cholangitis
Acute pankreatitis
Liver abscess
3,3%
0%
3,7%
6,3%
14,3%
of 211 patients
of 79 patients
of 81 patients
of 32 patients
of 7 patients
Tab. No.6 - Mortality of patients with biliary tract infection

The course of therapy and clinical efficiency were significantly influenced by the simultaneously occuring secondary illnesses as well as current needs for surgical or radiologic intervention.

Conclusions

The study of treatment of biliary tract infections by cefoperazon showed a very good clinical (90%) and bacteriological (91.3%) effectiveness. Cefoperazon was administered mainly empirically in the initial antimicrobial treatment (87%). The effectiveness of the treatment significantly affected the secondary associated illnesses. High effectiveness was noted in the treatment of acute cholecystitis (99%) and acute cholangitis (89%). The mortality of patients with acute cholangitis was 3.7%, in the group of patients with liver abscesses it was 14.3%.
Cefoperazon may be considered a suitable drug for safe and efficient initial antibiotic therapy in patients with biliary tract infections.

References

  1. Kolář, M., Lovečková, Y. Antibioterapie infekcí žlučových cest. Interní medicína pro praxi, 1999, roč. 4. s. 21 - 25.
  2. Forssmann, K., Singer, M.V. Acute Cholecystis - Conservative Therapy. Schweiz. Rundschau Med. (PRAXIS). 1994, roč. 83, s. 877 - 879.
  3. Lochmann, O. Antimikrobní terapie při infekcích žlučových cest. Bulletin HPB, 1997, roč. 5, Suppl. 1, s. 6 - 8.
  4. Leung, J. W. C., Chan, R.C. Y. et al. The effect of obstruction on the biliary excretion of cefoperazone and ceftazidime. Journal of Antimicrobial Chemotherapy, 1990, roč. 25, s. 399 406.
  5. Cefobid - souhrn údajů o přípravku. Praha: Pfizer, spol. s. r. o ., 1995.
  6. Berger, S. A., et al. Penetration of cefazolin, cefriaxone, cefoperazone and ceftazidime in human gallblader tissue and bille. World J. Surg., 1998, roč. 32, č. 8, s. 1231 - 1236.
  7. Mashimo, K. Clinical Experience with Cefoperazon in Biliary Tract Infections. Drugs, 1981, roč. 22, Suppl. 1, s. 100 - 107.
  8. Vyhnánek, F., Lochmann O., Pelák, Z. Cefoperazon v léčbě infekcí žlučníku , žlučových cest a jater u chirurgických nemocných. Rozhl. Chir., 1996, roč. 75, č. 11, s. 544 - 548.

Address for correspondence:

Doc. MUDr. Vlastimil Procházka, Ph.D.
2nd Internal Clinic of Faculty Hospital Olomouc
I. P. Pavlova 6
775 20 Olomouc
Czech Republic