Introduction

Although only 5±10 % of patients admitted to hospitalare treated in intensive care units (ICUs), most of thehospital acquired infections are seen in these units. Therate of hospital infection in the ICU is 5±10-fold higherthan in other units (1±4).

The high rate of hospital infection also leads to use ofa wide range of antibiotics. In this study, the influencesof the alternative use of imipenem and cefoperazone/sulbactam and of a regular daily infectious diseases con-sultation on antibiotic sensitivity rates in the ICU werestudied.

Materials and methods

The study was performed in the eight-bed ICU where the surgicaland medical patients requiring ventilator support were treated.The antibiotic sensitivity results from 1 April 1993±1 April 1994were compared to those of 1 April 1995±1 April 1996. The results

of cultures of deep endotracheal aspirate, blood, urine, wounds,drain, cerebrospinal fluid and catheters (colonization or infection)from the patients were used for the evaluation.

Identification of microorganisms and antibiotic sensitivity testswas performed using the Sceptor Microbiological Diagnosis Sys-tem (Becton-Dickinson Microbiology Systems, Cockeysville, Md.,USA), and antibiotic sensitivity was determined according to mini-mal inhibitory concentration values using National Committee forClinical Laboratory Standards (NCCLS) criteria. The Kirby-Bauerdisk diffusion method was employed for determining the sensitivi-ty of cefoperazone/sulbactam [5].

Between 1 April 1993 and 1 April 1994, infectious diseases con-sultants visited and examined patients when needed and there wasno alternative therapy protocol. From 1 April 1994 throughout thenext 2 years the same consultant followed up every patient in theICU by regular daily visits and an alternative therapy protocolwas initiated at random. The results of antibiotic sensitivity inthese two different periods were retrospectively evaluated.

The protocol used during the daily visits was as follows: (1)When an infection developed, antibiotic treatment was initiatedby alternating cefoperazone/sulbactam and imipenem, and therapywas modified according to antibiotic sensitivity results. (2) Quinol-ones were removed in the empirical therapy protocol because of ahigh rate of resistance. (3) Basic infection control techniques were

H. AkalõnF. KahveciC. ÖzakõnS. HelvacõS. GedikogÆ luO. KutlayO. Töre

Influences of alternate therapy protocoland continuous infectious diseaseconsultation on antibiotic susceptibilityin ICU

Received: 18 December 1998Final revision received: 14 June 1999Accepted: 18 June 1999

H. Akalõn ()) ´ C. Özakõn ´ S. Helvacõ ´S.GedikogÆlu ´ O.TöreUludagÆ University, School of Medicine,Department of Microbiologyand Infectious Diseases,16059 Görükle, Bursa, Turkeye-mail:halis@uludag.edu.trFax: + 90(2 24)4428331

F.Kahveci ´ O.KutlayUludagÆ University, School of Medicine,Department of Anesthesiologyand Reanimation, Bursa, Turkey

Abstract In this study, the effects ofalternate use of imipenem and cef-operazone/sulbactam(CFP/Sul) onantibiotic resistance in the intensivecare unit (ICU) were investigated.Between 1 April 1993 and 1 April1994, the infectious diseases con-sultant saw patients when requiredand there was no alternative therapyfor antibiotics. For the following2 years, the same consultant fol-lowed up each patient from admis-sion to discharge by daily visits tothe ICU and an alternative therapyprotocol was initiated. The mostcommon microorganisms were

found to be Acinetobacter bauman-nii and Staphylococcus aureus, fol-lowed by Pseudomonas aeruginosaand Klebsiella pneumoniae, respec-tively, in the two periods. This studydemonstrated that sensitivity ratesof imipenem, ciprofloxacin and am-inoglycosides were improved as aresult of this protocol.

Key words Alternate use ofantibiotics

Intensive Care Med (1999) 25: 1010±1012Ó Springer-Verlag 1999 BRIEF REPORT

regularly discussed with nurses in one to one sessions. (4) Antibiot-ic sensitivity and incidence of microorganisms were regularly fol-lowed up.

The mortality in both periods of the study was also compared.The chi-square test was used for statistical analysis.

Results

Among the species isolated in the two periods, Acineto-bacter baumannii and Staphylococcus aureus were themost frequent bacteria, followed by Pseudomonas aeru-ginosa and Klebsiella pneumoniae. A comparison of theantibiotic sensitivity of A. baumannii between the twoperiods showed significant increases in the sensitivityto amikacin, ciprofloxacin and imipenem in 1995(p < 0.001, p < 0.01 and p < 0.01, respectively). In con-trast, an insignificant decrease in the sensitivity to cef-operazone/sulbactam was seen (Table 1).

The sensitivity of P. aeruginosa to amikacin, ceftazi-dime, cefoperazone, ciprofloxacin, gentamicin and im-ipenem was found to be significantly increased (p <0.01, p < 0.01, p < 0.001, p < 0.001, p < 0.001, p < 0.01,respectively) (Table 2). In addition, K. pneumoniaeshowed significantly increased sensitivity to amikacin,ceftazidime, cefoperazone, ciprofloxacin, ceftriaxoneand gentamicin (p < 0.001, p < 0.01, p < 0.05, p < 0.001,p < 0.01, p < 0.001, respectively) (Table 3).

The rate of Methicillin Resistant StaphylococcusAureus (MRSA) was 60% in the first period and 50%in the second period.

In 1993, 171 patients were followed up and the mor-tality was 39%, with 68 deaths. In 1995 the mortalitywas also 39% with 79 deaths out of 192 cases. Therewere no significant differences in mortality betweenthe two periods.

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Table 1 Results of antibiotic sensitivity (%) of A. baumannii in 1993 and 1995

CFP-SUL AN* CAZ CFP CIP** CRO GM IPM**

1993No. of isolates testedAntibiotic sensitivity (%)

2475

1061

614

500

10616

1072

920

8562

1995No. of isolates testedAntibiotic sensitivity (%)

7767

9529

957

950

9532

950

954

9581

* p < 0.001; ** p < 0.01 when results of 1993 and 1995 are compared (CFP-SUL cefoperazone-sulbactam, AN amikacin, CAZ ceftazi-dime, CFP cefoperazone, CIP ciprofloxacin, CRO ceftriaxone, GM gentamicin, IPM imipenem)

Table 2 Results of antibiotic sensitivity (%) of P. aeruginosa in 1993 and 1995

CFP-SUL AN** CAZ** CFP* CIP* CRO GM* IPM**

1993No. of isolates testedAntibiotic sensitivity

850

7140

5135

478

7237

660

682

6346

1995No. of isolates testedAntibiotic sensitivity

3675

4369

4362

4344

4376

430

4346

4374

* p < 0.001; ** p < 0.01 when results of 1993 and 1995 are compared CFP-SUL cefoperazone-sulbactam, AN amikacin, CAZ ceftazidime,CFP cefoperazone, CIP ciprofloxacin, CRO ceftriaxone, GM gentamicin, IPM imipenem)

Table 3 Results of antibiotic sensitivity (%) of K. pneumoniae in 1993 and 1995

CFP-SUL AN* CAZ* CFP*** CIP* CRO** GM* IPM

1993No. of isolates testedAntibiotic sensitivity (%)

540

2917

190

160

2920

290

250

2470

1995No. of isolates testedAntibiotic sensitivity (%)

3470

3688

3633

3630

3686

3627

3641

3686

* p < 0.001; ** p < 0.01; *** p < 0.05 when results of 1993 and 1995 are compared

Discussion

Intensive care units are one of the critical hospital envi-ronments where resistant bacteria are found most exten-sively. Basic infection control techniques can reducetransmission from the environment. Antibiotic protocolsplay important roles in the appearance of resistant mi-croorganisms. Use of a single antibiotic extensively canlead to the appearance of resistant microorganisms, and,in addition, epidemics in ICUs with these microorgan-isms may occur [6±9]. In our unit, third-generation ceph-alosporins such as cefotaxime, ceftriaxone and ceftazi-dime were extensively used before 1994. The presenceof a high resistance to ceftazidime and ceftriaxone buthigh sensitivity to cefoperazone/sulbactam and imipe-nem in K. pneumoniae strains indirectly suggest that theresistance may be due to extended-spectrum beta-lacta-mases (ESBL), which may appear under the selective in-fluence of extensive usage of third generation cephalo-sporins. In recent years, it has been suggested that cyclingof antibiotics in 2-month periods may be effective to pre-vent the development of resistant microorganisms [10].Our study suggests that frequent changes in empiricaltherapy and removal of ciprofloxacin from empiricaltherapy protocols provided a significant improvementin the sensitivity rates of all three microorganisms (P.aeruginosa, K. pneumoniae, A. baumannii).

During our study, we used cefoperazone/sulbactamand imipenem alternately in empirical therapy because

other suitable regimens such as sefepim, ticarcillin/cla-vulanic acid and piperacillin/tazobactam were not avail-able in our country.

The alternate use of imipenem and cefoperazone/sulbactam, especially, prevented the extensive and con-tinuous use of these antibiotics and caused loss of resis-tant A. baumannii and P. aeruginosa. Significant in-creases in the sensitivity of K. pneumoniae to third gen-eration cephalosporins and amikacin may be explainedby the reduction of ESBL-producing K. pneumoniae[11].

We demonstrated that continuous infectious diseasesconsultation (regular daily visits), surveillance, an alter-native therapy protocol and use of basic infection con-trol techniques, which included use of chlorhexidine forhandwashing, educating health workers, nurses and oth-er staff about handwashing and wearing gloves, use ofdisposable ventilator circuits and reduction of patientnumbers to two per nurse, played a significant role inobtaining these results. However, it has to be notedthat these results were achieved without any change inmortality.

Therefore, we recommend that infectious diseasesconsultants should visit the same unit for a long time pe-riod and should initiate the alternative therapy protocol.We suggest that this strategy can prevent or delay thedevelopment of resistance.

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