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Department of Surgical Intensive Care Unit, Onassis Cardiac Surgery Center, 356 Sygrou Avenue, 17674 Athens, Greece
Received 5 November 2007; received in revised form 5 February 2008; accepted 6 February 2008.
* Corresponding author. Address: 29, Irodoutou Street, 15122, Maroussi, Athens, Greece. Tel.: +30 210 8063790; fax: +30 210 9493333. (Email: dr_kamast{at}yahoo.gr).
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Abstract |
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 Top Abstract 1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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Key Words: Acinetobacter baumannii • Cardiac surgery • Preventing strategy
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1. Introduction |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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2. Material and methods |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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Data variables extracted for evaluation in each case of MDR-AB infection included: demographics, dates of admission and discharge, transfer from another institution, infection on ICU admission, previous nosocomial infection, surgical procedure, the nature of complication, pre-existing medical conditions, comorbidities, presence of prosthetic material or intra-vascular devices and the outcome including hospital discharge diagnoses, SICU length of stay and mortality rate. Additional data regarding infectious complications were also included: positive bacterial cultures, antibiotic susceptibilities, antibiotics administered, dates and sites of the first isolation of the MDR bacteria, subsequent cultures results and the duration of colistin treatment. Side effects related to colistin as well as the concomitant use of other drugs that could potentially cause nephrotoxicity were also registered.
Furthermore, we reviewed the prophylactic measures of the SICU and implemented a two scale multiple program. Scale I included classical infection control measures, i.e. strict contact and droplet isolation, surveillance of throat, nasal and anal flora for MDR pathogens on all patients transferred from other hospitals, separate nursing staff for each infected or colonized case and strict antibiotic policy, while scale II referred to the geographic isolation of all positive MDR-AB cases in distinct hospital units with exclusive medical and nursing personnel, use of separate supplies and facilities and environmental intense surveillance. Therefore, scale II prophylactic measures were mandatory and promptly implemented after the detection of AB strains in order to prevent the spread of the pathogen.
Standard media and techniques for bacterial isolation and identification were used. The breakpoints for susceptibility were those recommended by the Clinical Laboratory Standards Institute. Antibiotic susceptibility was determined for the following antimicrobial agents: piperacillin, piperacillin/tazobactam, ticarcillin/clavulanic acid, aztreonam, ceftazidime, cefepime, imipenem, meropenem, tobramycin, amikacin, gentamicin, ciprofloxacin and colistin with the disk diffusion method. With regard to colistin 10 µg disk an inhibition zone of <11 mm was accepted as the cut-off to confirm resistance. Isolates were classified as susceptible, intermediate or resistant according to standard criteria [6]. MICs of antibiotics were determined by the E-test method and were interpreted in accordance with national guidelines [7]. At the beginning of each outbreak carbapenemase detection was also performed by measuring hydrolysis of imipenem with UV spectrophotometry and PCR.
Diagnosis of pneumonia required the presence of new, persistent and otherwise unexplained pulmonary infiltrates appearing on the chest radiograms. Moreover, at least two of the following criteria were also mandatory: (i) temperature of >38 °C; (ii) leucocytosis of >10,000 cells/mm3 or leucopenia; and (iii) purulent respiratory secretions. Tracheobronchial secretions and/or bronchoalveolar lavage (BAL) specimens were used for microbiological diagnosis of pneumonia using non-quantitive cultures. Other infections, such as urinary tract infections and central venous catheter-related infections, were defined based on the guidelines issued by CDC. If bacteremia was suspected, at least two blood samples were obtained for culture from separate sites before the initiation of therapy.
On isolation of strains of AB that were resistant to all potentially active antibiotics apart from colistin, intravenous colistin was initiated at the discretion of the attending physician. All patients received intravenous colistin sulphomethate sodium at a dose of 3,000,000 IU every 8 h, with 1 mg of the colistin used being approximately equal to 13,333 IU (Norma, Athens, Greece). Dosage adjustments were made according to creatinine clearance in patients with renal failure. For patients receiving dialysis treatment, the dosage was adjusted to 1,000,000 IU after each period of dialysis. Aerolized colistin was administered at a dosage of 500,000 IU every 8 h.
Clinical cure was defined as resolution of presenting symptoms and signs of infection by the end of colistin treatment, while clinical improvement as partial resolution of these signs. Clinical failure was defined as persistence or worsening of presenting symptoms during colistin administration (unresponsiveness) and recurrence of infection as the occurrence of a new episode of infection at least 72 h after clinical resolution of a preceding episode. Eradication of the pathogen was defined as absence of growth in the final culture of specimens. Safety of the drug was assessed on the basis of laboratory test results for renal function during colistin administration. Normal renal function was defined as a serum creatinine level of <1.2 mg/100 ml.
The Institutional Review Board approved the study, but since only routine clinical and laboratory examinations were evaluated no ethical committee approval was necessary.
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3. Results |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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All patients were treated with intravenous colistin in combination with aerolized colistin. At the induction of anesthesia all patients who were submitted to coronary artery bypass grafting (CABG) received cefuroxime intravenously as a single dose of 3 g, while patients who underwent valvular replacement were administered a combination of two doses of 400 mg teicoplanin and three doses of 2 g ceftazidime for 24 h. Previous antimicrobial therapy included a carbapenem (16 cases), or piperacillin/tazobactam (12 cases), or aminoglycoside (16 cases), or fluoroquinolone (10 cases). Concurrently, eight patients received a glycopeptide for the treatment of bacteremia caused by a gram-positive coccus. In addition, all patients received inotropic agents.
Clinical cure or improvement was observed in four patients (20%), while 16 patients did not respond to colistin; they developed sepsis and multiple organ failure (MOF). All deaths occurred in the SICU. Eradication of the pathogen was observed in three cases. Only one patient in the study submitted to implantation of artificial heart appeared with a recurrent nosocomial infection caused by the same MDR strain of AB. Aerolized colistin was administered even after the cessation of intravenous therapy until the eradication of the pathogen was confirmed in two consecutive cultures of samples associated with the specific site infection. Colistin associated side effects were not documented. With regard to nephrotoxicity, six patients had an identified renal insufficiency at SICU admission (serum creatinine >2.5 mg/100 ml) before colistin administration. They all developed acute renal failure and were treated with continuous venovenous hemodiafiltration (CVVHD). The rest of the patients (n: 14) had a serum creatinine below 2.5 mg/100 ml and adequate diuresis.
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4. Discussion |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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AB represents multiple biotypes and plasmid types [9]. Resistance to b-lactams antimicrobials is often due to the production of PER-1 extended-spectrum b-lactamases [10] as well as alterations in the penicillin-binding proteins, the reduction in porins’ expression and the presence of OXA-derived b-lactamases [11]. The relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expression in AB strains has also been published [12]. Furthermore, nosocomial isolates of AB exhibit high rates of quinolone resistance [13].
Carbapenems appear to be a valuable option for the treatment of severe nosocomial infections caused by PA and AB strains [14]. Nevertheless, considerable overuse of imipenem resulted in the emergence and rapid dissemination of MDR pathogens in ICUs [15]. Several outbreaks attributed to MDR-AB epidemic strains that harbor a carbapenem-hydrolyzing enzyme have been reported [11]. Furthermore, European studies confirmed the spread of the VIM metallo-b-lactamases as the determinant of carbapenem resistance in MDR gram-negative bacilli isolates [16].
In our study colistin proved the only antimicrobial agent effective against AB strains. Colistin has not been used greatly since the early 1980s because of its potential toxicity, except in patients with cystic fibrosis [17]. It is a cationic polypeptide antibiotic of the polymyxin family that is rapidly bactericidal to gram-negative bacteria. The action of colistin is by a detergent-like mechanism, interfering with the structure and function of the outer cytoplasmic membrane of bacteria and resulting in their death [18]. It remains active against almost all strains of P. aeruginosa, Klebsiella pneumonia, Acinetobacter spp. and Enterobacter spp.
Clinical experience regarding the use of colistin in severely ill patients is limited. Levin et al [1] reported that favorable response of nosocomial infections caused by P. aeruginosa and Acinetobacter spp. was 60%, although a major side effect was renal insufficiency. Michalopoulos et al. [19] demonstrated that beneficial clinical outcome was observed with 74.4% of patients and eradication of the pathogen was obtained for 67.4% of the patients. In another study from Spain, Garnacho-Montero and co-workers [4] reported the only controlled study of colistin in patients with cystic fibrosis and identified 21 patients with ventilator-associated pneumonia caused by bacteria susceptible only to colistin with a curative rate of 57%. Finally, Ouderkirk et al. [5] suggested that the mortality rate for patients with infections caused by MDR gram-negative bacteria treated with polymyxin B was 20%, while Markou et al. [18] elucidated that survival at 30 days was 57.7%. In the present survey clinical response was obvious in 20% of the patients evaluated. However, differences in mortality should be interpreted with caution because of potential differences in patient characteristics or virulence of the pathogen. Our study confirms the therapeutic insufficiency of colistin against MDR-AB strains, although the drug achieved a curative rate of 70% against MDR P. aeruginosa strains. Exposure to invasive devices and procedures remains a major predisposing factor for acquisition of AB infections [20]. In our investigation one patient received an artificial heart while the implantation of intra-aortic balloon pumping (IABP) was implemented in 12 patients.
Earlier reports determined a high incidence of colistin toxicity [21]. Renal injury remains the major adverse effect of colistin. In the study conducted by Koch-Weser and co-workers [22], impairment in renal function, usually reversible with termination of treatment, was observed in 20.2% of 288 patients. Markou et al. [18] suggested that, despite a dosage of colistin much higher than that usually reported, nephrotoxicity was moderate (14.3%). Furthermore, experience with the drug in patients with cystic fibrosis proved only minimal nephrotoxicity [23]. The present findings are in accordance with other reports published recently as deterioration of pre-existing renal dysfunction was observed in 30% of the patients examined. Nevertheless, it is unlikely that colistin had a clinically remarkable impact in these cases with a history of chronic renal failure, as this group of patients often develops nosocomial infections for which other potentially nephrotoxic agents may be used, and has higher acute illness severity scores than patients with normal renal function [23]. Thus, the possibility of renal toxicity should be considered seriously, especially when colistin is used as the last resort in patients prone to renal insufficiency because of illness severity and the development of septic shock. Although neurotoxicity and neuromuscular blockade were also reported with colistin [22], no clinically evident or neurophysiologic abnormalities were observed in our patients.
Cross-resistance with other antibiotics has not been reported, and acquired resistance is rare [24]. Nevertheless, inadequate therapy of patients with MDR-AB strains creates demand on strict screening and contact precautions. Crowe et al. [2] support that MDR-AB was isolated from various environmental sites in ICU and patient and environmental isolates were correlated closely by biotyping, antibiograms, pulsed-field electrophoresis of chromosomes fingerprints and ribotyping. Other investigators report that barrier precautions, mapping patients’ movements on a timeline, environmental decontamination and staff education instituted in the ICU resulted in the significant reduction of colonization and infection with MDR-AB [9]. A review of hand hygiene and other infection control practices as well as a closed suctioning system has also been proposed [3].
In another survey [15], combined infection control strategy was designed and implemented, including the sequential closure of all ICUs for decontamination and strict compliance with cross-transmission prevention protocols. Transfer of infected or colonized patients to an isolated cubicle, cohort nursing, emphasis on the importance of hand washing before and after patient contact and when handling notes and the mandatory use of disposable gowns have also been advocated [2]. Furthermore, conversion from open to isolation rooms may contribute to the decrease of nosocomial bronchopulmonary tract acquisition of AB in mechanically ventilated patients [25].
In our institution a two scale multiple program was implemented. Scale I included classical infection control measures, i.e. strict contact and droplet isolation, surveillance of throat, nasal and anal flora for MDR pathogens on all patients transferred from other hospitals, separate nursing staff for each infected or colonized case and strict antibiotic policy, while scale II referred to the geographic isolation of all positive MDR-AB cases in distinct hospital units with exclusive medical and nursing personnel, use of separate supplies and facilities and environmental intense surveillance. Scale I measures were implemented for the whole 16-month period while scale II for two separate periods of 3 weeks until the complete elimination of MDR-AB infectious outbreak. Following this infection control strategy we were able to achieve intermittent eradication of the pathogen during a 16-month period with continuous function of the SICU.
Multi-resistant hospital acquired AB strains should be considered as a serious public health issue rather than an individual hospital's problem. Despite the significant ‘in vitro’ activity of colistin against MDR-AB the results were discouraging. Moreover, the small number of patients, the absence of a control group and the concomitant administration of other agents do not allow for a clear verdict on the effectiveness and safety of the drug. Due to the increased mortality of MDR-AB infected patients additional to scale I measurements are highly recommended.
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References |
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TopAbstract1. Introduction2. Material and methods3. Results4. DiscussionReferences |
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  L. K. von Segesser Post-cardiac surgery arrest: what to do in the ICU (intensive care unit) Eur. J. Cardiothorac. Surg., July 1, 2009; 36(1): 1 - 2. [Full Text] [PDF]
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