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Ann Thorac Surg 1999;68:208-211
© 1999 The Society of Thoracic Surgeons


Original Articles

Preoperative microbiologic screening and antibiotic prophylaxis in pulmonary resection operations

Joachim Boldt, MDa, Sven Piper, MDa, Dirk Uphusb, Roswita Füssle, MDc, Gunter Hempelmann, MDb

a Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Germany
b Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig-University, Giessen, Germany
c Institute of Microbiology, Justus-Liebig-University, Giessen, Germany

Address reprint requests to Dr Boldt, Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Bremserstrasse 79, D-67063 Ludwigshafen, Germany


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Background. Pulmonary resection is associated with considerable risk of infection, so antibiotic prophylaxis has become routine practice in pulmonary operations. We studied two standard flash antibiotic prophylaxis regimens and matched them to preoperatively acquired microorganisms.

Methods. In 120 patients scheduled for elective pulmonary resection, aspirates were taken separately from the left and the right lung using a double-lumen tube. Then the patients received either 1.5 g of sulbactam plus ampicillin (n = 60; group 1) or 2 g of cefazolin (n = 60; group 2) intravenously as a single-shot antibiotic prophylaxis according to a prospective randomized sequence. When bacteria were found in the aspirates, both antibiotics were tested for susceptibility. The patients were monitored for the first 3 postoperative days with regard to bronchopulmonary infections.

Results. Fifty-eight pathogens were isolated from the 120 patients. The cultured bacteria did not differ significantly between the two groups. In group 1 all found bacteria were susceptible to the used antibiotic prophylaxis, whereas in group 2 eight of the 25 found bacteria were not susceptible to antibiotic prophylaxis. Postoperatively, group 2 showed significantly more signs of bronchopulmonary infections than the group 1 and subsequently needed additional antibiotics more often. Intensive care unit stay was longer in patients of group 2 and costs were higher for these patients.

Conclusions. Preoperative microbiologic examination could be helpful to evaluate efficacy of the antibiotic prophylaxis regimen. Sulbactam plus ampicillin was significantly more effective than cefazolin.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Antibiotic prophylaxis is recommended in clean-contamined surgery such as pulmonary surgery. Of patients who have lung operations, 12% to 40% had postoperative infections, eg, bronchopneumonia, wound infections, and empyemas [13]. Thus prophylactic antibiotics are used routinely in patients who have thoracic surgery to prevent infective complications [4]. Various antibiotics can be given intravenously for this purpose[46]. It is important that antibiotics used for prophylaxis are chosen correctly for the lung flora because inappropriate prophylactic antibiotics can lead to development of resistant strains and can also increase costs considerably. Various antibiotics have been used for prophylaxis in noncardiac thoracic operations, but the ideal substance still has not been determined. Which antibiotic regimen is most effective depends also on the bacteria that are present preoperatively. Thus in the present study microbiologic examinations were done preoperatively and efficacy of two different regimens of single-dose antibiotics were tested.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
After review and approval by the Ethics Study Board of the hospital and informed consent was obtained, 120 consecutive patients with primary lung cancer who had first-time, elective lung resection (lobectomy, bilobectomy, or pneumonectomy) were studied. None of the patients received antibiotics during the 14 days before the operation. None of the patients had any clinical (normal temperature) or laboratory signs of infection (normal leukocyte count). Patients with obstructing cancer and patients using cortisone or other immunodepressive substances were not included in the study. All patients showed normal hepatic (serum bilirubin < 15 µmol/L, aspartate aminotransferase [AST] < 20 U/L, alanine aminotransferase [ALT] < 20 U/L) and renal function (serum creatinine < 1.2 mg/dL).

Induction and maintenance of anesthesia were carried out using weight-related doses of fentanyl, midazolam, and pancuronium. No volatile anesthestics were used. All patients were intubated with a double-lumen endobronchial tube to perform atelectasis of the operated lung (one-lung ventilation). Immediately after the double-lumen tube was placed, aspirates were taken selectively from the right and left sides of the lung. Aspirates were immediately sent for microbiologic examination. According to a randomized sequence the patients were then separated into two groups: group 1 (n = 60) received a single dose of 1.5 g of ampicillin plus sulbactam (combined with a beta-lactamase inhibitor), and group 2 (n = 60) received 2 g of cefazolin (a basic cephalosporine).

Bronchoscopy was done postoperatively in all patients to explore the bronchial stump. The double-lumen tube was replaced by a standard tube, and controlled mechanical ventilation was continued in the intensive care unit until the patients breathed sufficiently spontaneously, cardiorespiratory parameters remained stable for at least 30 minutes, and temperature was higher than 36°C.

Extensive intercostal nerve blockade was performed directly by the surgeons before chest closure. In the ICU, additional intercostal nerve blockade was used or piritramide (a morphine derivative) was given whenever the patient felt pain. The entire perioperative therapeutic management of the patients (volume replacement, pharmacologic support, ventilation patterns, and antibiotic therapy) was done by physicians who were not involved in the study and who were unaware of the grouping.

Measured parameters
In cases of positive microbiologic cultures, the bacteria were identified and tested for sensitivity to the two antibiotics. Leukocyte count and C-reactive protein levels were measured from central venous blood samples preoperatively (baseline data), at arrival in the ICU, on the morning of the first, second, and third postoperative days. Chest roentgenograms were done postoperatively and daily on postoperative days 1 through 3 and were assessed by physicians who were not involved in the study and unaware of the grouping. The following evaluation scores were defined: no signs of bronchopneumonia = 0, local or moderate bronchopneumonia = 1, and massive bronchopneumonia = 2. When patients showed signs of infection (temperature higher than 38°C, leukocyte increase of more than 50% of baseline data, positive chest roentgenogram) intravenous ciprofloxacin (2 x 200 mg) was started and continued until bronchopulmonary infection was sucessfully treated.

Acquisition costs for antibiotics were derived from the hospital’s pharmacy list (cefazolin, $3.11/2 g; ampicillin plus sulbactam, $4.26/1.5 g; ciprofloxacin, $47.30/400 mg). Cost analyses did not include specific costs for ICU staff (physicians, nurses) and disposable instruments (cannula, infusion lines). According to data taken from the hospital’s internal clearing system, 1 day in our ICU costs $694.

Statistics
All values are expressed as mean ± standard deviation. Data analysis included a nonparametric analysis of variance (Kruskal-Wallis), t test, and two-way analysis of variance for repeated measures of the same variable (analysis of variance followed by Scheffé test [for serially measured data]). A p value less than 0.05 was considered significant.


    Results
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 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
The two groups did not differ with regard to demographic and perioperative data (Table 1). There was no difference in the number of peripheral versus central tumors between the two groups. The kind of pulmonary operation also did not differ. One patient in each group died secondary to multiple-organ dysfunction syndrome, which was not related to pulmonary infection (low output syndrome secondary to myocardial infarction). Bronchopulmonary infection was diagnosed more often from chest roentgenograms in group 2 (n = 10) than in group 1 (n = 2) (Table 1). Significantly more patients in group 2 (n = 10) than in group 1 (n = 2) needed additional antibiotics (Table 1). Patients in group 2 stayed significantly longer in the ICU than patients in group 1 (Table 1). Leukocyte count, C-reactive protein level, and temperature were significantly higher in group 2 than in group 1 (Table 2).


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Table 1. Demographic and Perioperative Data

 

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Table 2. Laboratory Data and Temperature in the Two Groups

 
A total of 58 pathogens were isolated from the 120 patients: 23 pathologic bacteria were found in patients in group 1, whereas 25 bacteria were obtained from patients in group 2 (Table 3). The panel of cultured bacteria did not differ significantly between the two groups. In 58 patients pathologic bacteria were found in the operated (cancerous) lung, and in 45 pathologic bacteria were found in the opposite side (Table 3). Antibiogram revealed susceptibility to all found bacteria in group 1, whereas in group 2, eight of the 25 found bacteria were not susceptible to the antibiotic prophylaxis (no efficacy in 13% of all patients; 32% of the found pathologic bacteria were not susceptible).


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Table 3. Bacteria Found in the Preoperatively Acquired Aspirates

 
Analysis of total acquisition costs of antibiotics revealed significantly higher costs for patients treated with cefazolin (group 2) than for patients treated with sulbactam plus ampicillin (group 1) (Table 4). The additional use of antibiotics and the prolonged stay in the ICU increased costs for group 2 considerably (Table 4).


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Table 4. Cost Analysis

 

    Comment
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Patients scheduled for resection of the lungs are prone to develop infections [7]. Most have a history of severe smoking with subsequent impairment in ciliary mobility and altered bronchial mucosa. Routine antibiotic prophylaxis in pulmonary operations remains controversial, but its use has become standard practice. A variety of organisms must be considered as potential pathogens, eg, gram-negative (Escherichia coli, Klebsiella pneumonia, Haemophilus influenzae) and gram-positive organisms (Staphylococcus aureus) [8]. In thoracic surgical procedures including lobectomy and pneumonectomy, prophylaxis using cefazolin (2 g) has been recommended. First-generation cefalosporines, however, were shown to be ineffective against gram-negative bacteria or against Staphylococcus aureus [3], whereas second-generation cephalosporins appeared to fit the bacteria encountered during lung operations [1].

One finding of interest was that the panel of cultured bacteria was different between the cancerous lung and the other lung. Thus microbiological examination from aspirates obtained by a single-lumen tube might not be representative of the causative bacteria of infection.

Another result was that the regimen of preoperatively used antibiotics might not be directed correctly against the bacteria encountered in pulmonary operations. In 13% of the patients who received a single dose of cefazolin, that strategy of antibiotic prophylaxis was ineffective; up to 32% of the bacteria were not susceptible to that substance. The most common bacterial organism was Haemophilus influenzae. In patients who received sulbactam plus ampicillin, no lack of susceptibility was seen. Postoperatively, the bronchopulmonary infection rate was significantly lower in the patients who received sulbactam plus ampicillin, and subsequent use of additional antibiotics was lower and ICU stay was significantly shorter than in the other group. All patients infected with H influenzae showed signs of pneumonia (infiltration on chest roentgenogram) and signs of infection (leukocyte count, temperature increase). All patients were extubated and breathed spontaneously. Because we never use sputum for microbiologic analysis and bronchoscopy was not necessary, we unfortunately did not know possible causative bacteria in patients who developed infection several days postoperatively.

Efficacy of ampicillin in combination with sulbactam, a beta-lactamase inhibitor, was also shown in a study in patients who had general thoracic operations [9]. Use of ampicillin or comparable substances (eg, amoxicillin) appeared to be ineffective for antibiotic prophylaxis. In a study of 256 patients who had pulmonary operations, patients treated with amoxicillin showed significantly more infections than patients treated with cefamandole (a second generation cefalosporine) [10]. In this study, H influenzae was also an important bacterial organism for infection. The beta-lactamase of our combination (sulbactam plus ampicillin) was important for our beneficial results. Other studies, however, reported that penicillin was sufficient for antibiotic prophylaxis. In a double-blind randomized study, Krasnik and colleagues [11] compared penicillin (5 million IU) with 1.5 g cefuroxime (an intermediate cephalosporine). They found no intergroup differences with regard to postoperative empyema, pneumonia, or wound infections.

Acquisition costs were slightly higher in the ampicillin plus sulbactam group than in the cefazolin group. When additional antibiotic therapy was included, however, the cefazolin group had significantly higher acquisition costs. Moreover, because of the longer stay in the ICU, costs for the cefazolin group were considerably higher.

Determination of preoperatively acquired microorganisms might help to identify the ideal antibiotic prophylaxis regimen in patients scheduled for lung operations. Antibiotic single-dose prophylaxis regimen using sulbactam plus ampicillin lowered the incidence of bronchopulmonary infection after lung operations, reduced additional costs for antibiotics, and was associated with shorter stay in the ICU compared with antibiotic prophylaxis with cefazolin.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

  1. Bernard A., Pillet M., Goudet P., Viard H. Antibiotic prophylaxis in pulmonary surgery. J Thorac Cardiovasc Surg 1994;107:896-900.[Abstract/Free Full Text]
  2. Tarkka M., Pokela R., Lepojarvi M., Nissinen J., Karkola P. Infection prophylaxis in pulmonary surgery. Ann Thorac Surg 1987;44:508-513.[Abstract]
  3. Olak J., Jeyasingham K., Forrester-Wood C., et al. Randomized trial of one dose versus six dose cefazolin prophylaxis in elective general thoracic surgery. Ann Thorac Surg 1991;51:956-958.[Abstract]
  4. Conte J.E., Jr Antibiotic prophylaxis and abdominal surgery. In: Remington J.S., Swart M.N., eds. Current clinical topics in infectious disease. Boston: Blackwell Scientific, 1989:254-305.
  5. Simon C., Stille W., Wilkinson P.J. Antibiotic therapy. Stuttgart: Schattauer, 1993:613-616.
  6. Frey D.J.M., Reichmann A.K., Potchinkow J., Kaiser D. Prophylaxis of pneumonia after lung surgery in risk-patients?. Thorac Cardiovasc Surg 1992;40(Suppl):100-101.
  7. Kelly J. State of the art. Am Rev Respir Dis 1990;141:765-788.[Medline]
  8. Martin C., Ragni J., Lockiec F. Pharmacokinetics and tissue preparation of a single dose ceftriaxone (1,000 mg intravenously) for antibiotic prophylaxis in thoracic surgery. Antimicrob Agents Chemother 1992;36:2804-2807.[Abstract/Free Full Text]
  9. Wertzel H., Swoboda L., Joos-Wutemberger A., Frank U., Hasse J. Perioperative antibiotic prophylaxis in general thoracic surgery. Thorac Cardiovasc Surg 1992;40:326-329.[Medline]
  10. Train M., Soulard D., Bouyler L., Bizouarn P., Blanloeil Y. Comparison of amoxicillin and cefamandole in the prevention of bronchopulmonary infections in pulmonary surgery. A randomized double-blind study. Ann Fr Anesth Reanim 1994;13:280-284.[Medline]
  11. Krasnik M., Thiis J., Frimodt-Moller N. Antibiotic prophylaxis in non-cardiac thoracic surgery. A double-blind study of penicillin vs. cefuroxime. Scand J Thorac Cardiovasc Surg 1991;25:73-76.[Medline]
Accepted for publication January 18, 1999.




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