- Email: [email protected]
Burkholderia cepacia complex genomovars and pulmonary transplantation outcomes in patients with cystic fibrosis
RESEARCH LETTERS
enzyme immunoassay with baculovirus-based, recombinant VP2 protein (Biotrin, Dublin, Ireland) and calibrators (3·1, 6·25, 25, 50, and 100 IU) that allowed expression of results in IU. In non-immune individuals, the concentration of parvovirus-B19-specific IgG was usually lower than 5 IU, and seroconversion was assumed if it rose to more than 20 IU, although values exceeded 100 IU in most patients. Timing of infection was assumed to coincide with aplastic crises in those affected, and with the occurrence of abnormal haematology in patients with minor haematological change. In 43 patients without known haematological change, a window of seroconversion between the last negative and first positive sample was narrowed by assessment of further available samples within the window. Seven patients in whom the first positive sample showed IgM were assumed to have had infections within the preceding 3 months; in the remaining 36 patients, the event window had a median length of 61 weeks (IQR 40–143, range 19–280). These different methods of estimating timing of infection complicated assessment, but assumption that the event occurred at the midpoint in the interval window allowed us to use standard Kaplan-Meier methods; however, since this assumption could bias inferences and underestimate uncertainty, we also used a generalisation of the KaplanMeier estimate incorporating interval-censoring.4 Between June, 1973, and July, 2000, seroconversion occurred in 177 individuals, of whom 118 (67%) had clinical aplasia, 16 (9%) showed minor haematological change, and 43 (24%) were without known haematological change. Time to seroconversion by both Kaplan-Meier and Turnbull4 estimation were similar: 61% were affected by age 15 years and 70% by age 20 years (table 1). Only one patient with a clinically defined aplasia had no evidence of parvovirus B19 infection: a girl who became infected at age 9·3 years, who had a haemoglobin concentration of 24 g/L, zero reticulocytes, and who recovered normally after transfusion. She showed no evidence of parvovirus B19 IgG or IgM, and blood cultures were sterile. Haematological features in patients showing typical, minor, or no known haematological change are summarised in table 2. Assessed by normal regression, and after adjustment for baseline haemoglobin concentration, age at seroconversion, and sex, steady-state fetal haemoglobin was slightly higher in individuals with less haematological change during parvovirus B19 infection (p=0·03), but the number of ␣ globin genes had no effect. The arbitrary definition of aplastic crisis had a high predictive value: 118 of 119 clinically defined aplasias were associated with parvovirus B19 infection. This definition missed 16 patients with less characteristic haematological change and a further 43 individuals who, despite close monitoring, showed no known haematological change. Seroconversion in 61% of homozygous sickle-cell patients by 15 years, was similar to the 50% recorded among 11–15 year-olds in a British population,5 and is more consistent with clinical observations that aplastic crises in homozygous sickle-cell disease become uncommon after age 15 years. Virtually all clinically defined aplastic crises result from parvovirus B19 infection, but a third of infections do not manifest typical aplasia. After infection, immunity to further aplastic crises seems to be life-long and no recurrences occurred during 1859 patient-years of observation. The natural history of aplastic crisis is essentially benign since bone-marrow activity almost always resumes after 7–10 days aplasia, but deaths can result from extreme anaemia and from associated problems such as acute chest syndrome, nephrotic syndrome, and stroke. These features add urgency to the development of a human parvovirus vaccine.
1780
We thank Douglas Higgs (Weatherall Institute of Molecular Medicine, University of Oxford, UK) for the determination of ␣ globin gene number. 1
2 3
4 5
Serjeant GR, Topley JM, Mason K, at al. Outbreak of aplastic crises in sickle cell anaemia associated with parvovirus-like agent. Lancet 1981; 2: 595–97. Anderson MJ, Higgins PG, David LR, et al. Experimental parvoviral infection in humans. J Infect Dis 1985; 152: 257–65. Serjeant GR, Serjeant BE, Thomas P, Anderson MJ, Patou G, Pattison JR. Human parvovirus infection in homozygous sickle cell disease. Lancet 1993; 341: 1237–40. Turnbull BW. The empirical distribution function with arbitrary grouped, censored and truncated data. J R Stat Soc 1976; 38: 290–95. Brown KE. Human parvovirus B19 epidemiology and clinical manifestations. In: Parks WP, ed. Monographs in virology, vol 20. Basel: Karger, 1997: 42–60.
Sickle Cell Trust, 14 Milverton Crescent, Kingston 6, Jamaica (B E Serjeant FIBMS, Prof G R Serjeant MD); Sickle Cell Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston (I R Hambleton MSc); and Biotrin, County Dublin, Ireland (S Kerr PhD, C G Kilty PhD) Correspondence to: Prof Graham R Serjeant (e-mail: [email protected])
Burkholderia cepacia complex genomovars and pulmonary transplantation outcomes in patients with cystic fibrosis Anthony De Soyza, Andrew McDowell, Lynda Archer, John H Dark, Stuart J Elborn, Eshwar Mahenthiralingam, Kate Gould, Paul A Corris Burkholderia cepacia is a group of organisms that comprises seven genotypically distinct species (B cepacia genomovars I–VII), which are collectively known as the B cepacia complex. Preoperative infection with B cepacia is associated with a poor prognosis in lung transplant recipients with cystic fibrosis. Many centres do not, therefore, offer transplants to these individuals. Our aim was to ascertain whether or not post-transplant mortality is affected by pretransplant genomovar status. We studied archived isolates with PCR-based methods, and recorded excessive mortality in patients infected with B cepacia genomovar III, but not in those infected with other genomovars.
Lancet 2001; 358: 1780–81
Burkholderia cepacia causes pulmonary infection in 3–5% of patients with cystic fibrosis in UK and USA, although infection rates of 50% have been noted in some centres.1 B cepacia comprises seven genotypically distinct species, or genomovars, known as the B cepacia complex.2 Although all genomovars of this complex are capable of causing pulmonary infection in patients with cystic fibrosis, the most pathogenic are genomovar III and, to a lesser extent, genomovar II (B multivorans). Lung transplantation improves both the quantity and quality of life of patients with advanced cystic fibrosisassociated lung disease. However, lung transplantation outcomes are variable for patients colonised with B cepacia. Some studies have reported 1-year mortality rates of between 50% and 100%,1 however, survival rates greater than 75% have been noted.3 As a result of this potentially poor prognosis, many centres do not transplant individuals infected with B cepacia. We, however, do not deny individuals transplantation in the absence of other contraindications.4 We postulated that the disparity in posttransplant outcomes was dependent on the preoperative B cepacia complex genomovar responsible for infection.
THE LANCET • Vol 358 • November 24, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
RESEARCH LETTERS
Patient
Status post-transplant (days survived)
B cepacia complex genomovar
Antibiotic sensitivity
C-reactive protein (mg/L)
1 2 3 4 5 6 7 8 9 10 11
Alive (2400) Alive (1780) Alive (1125) Alive (274) Alive (156) Alive (80) Dead (10) Dead (27) Dead (31) Dead (35) Dead (36)
Unknown B multivorans B vietnamiensis B multivorans B vietnamiensis B multivorans Unknown B cepacia genomovar III B cepacia genomovar III B cepacia genomovar III B cepacia genomovar III
Unknown Multiresistant Multiresistant Multiresistant Panresistant Panresistant Multiresistant Panresistant Panresistant Panresistant Panresistant
180 Unknown Unknown 20 110 460 40 Unknown 680 250 30
White blood cell count (⫻1012/L) 11.5 11.8 11.2 10.5 12.1 15.0 20.6 23.3 13.3 14.0 10.9
Pretransplant temperature 36.8 37.2 37.1 36.5 36.1 36.8 37.2 36.5 37·0 37.6 37.7
Characteristics of pulmonary transplant recipients infected with Burkholderia cepacia complex
We reviewed our cystic fibrosis pulmonary transplant database, patient charts, and case notes. The immunosuppressive regimen used was similar to that previously described.1 Briefly, we made Clamshell incisions and prescribed prophylactic antibiotics according to the sensitivity of the bacterial isolates. If the isolate was pan-resistant,4 or unknown, 2 g aztreonam was given every 8 h for 2–7 days perioperatively. We assessed the clinical status of every patient immediately before the operation by measurement of bodymass index (BMI), core temperature, white cell count, and serum C-reactive protein concentration. We took samples of expectorated sputum during pretransplant assessment, immediately before surgery, and at post-transplant, and samples of postoperative bronchoalveolar lavage. We isolated B cepacia complex by selective culture, and identified them with the API20 NE phenotypic system (bioMerieux, Marcy l’Etoile, France). Antibiotic sensitivities were identified by disc diffusion. All pretransplant and post-transplant isolates were archived at ⳮ70°C pending PCR analysis,2 which was used to confirm that isolates were organisms of the B cepacia complex and to ascertain their genomovar status. We used Fisher’s exact test to measure post-transplant survival between patients who were and were not infected with B cepacia complex. 11 of 84 lung transplant recipients with cystic fibrosis had preoperative B cepacia complex infection (table). B cepacia complex organisms from nine of these individuals were successfully cultured from storage. We analysed 53 isolates, representing at least one pretransplant and day-of-transplant isolate and multiple post-transplant isolates from every patient. All isolates were identified as B cepacia by biochemical analysis. PCR-based analysis showed two patients were infected preoperatively with B vietnamiensis (genomovar V), three with B multivorans (genomovar II), and four with genomovar III. Immediate pretransplant and post-transplant genomovar status remained constant for every patient. Of the 11 patients with cystic fibrosis who were also infected with B cepacia complex, five died post-transplant because of progressive B cepacia related sepsis. Four of these patients had genomovar III infections. The genomovar infection in one patient who died was not identified; their archived isolates could not be cultured. All five patients were clinically unresponsive to cyclical antibiotics and thoracostomy drainage. B cepacia bacteraemia was found in four patients. The other six patients infected with B cepacia complex survived the early post-transplant period, and are making good progress. Archived samples from one survivor could not be cultured for genomovar designation. Of the five remaining patients, two were infected with B vietnamiensis (genomovar V) and three with B multivorans (genomovar II). The survival rates between genomovar III and non-genomovar III-infected patients differed significantly (100%; 95% CI 35–100; p=0·007). There were no clear differences between the B cepacia complex-infected survivor and non-survivor groups for BMI, core temperature, white cell count, and Creactive protein concentrations (table). The small numbers, however, limit analysis for potential confounding variables.
THE LANCET • Vol 358 • November 24, 2001
Our results show that patients with pretransplant genomavar III infections are at greater risk of death caused by B cepacia sepsis during the early postoperative period than those infected with B multivorans and B vietnamiensis, who have a good chance of surviving long-term post-transplant. The decision of some centres to place a moratorium on all patients with preoperative B cepacia infection might not, therefore, be justified. Further studies are needed to confirm our results before firm clinical conclusions can be drawn. Such studies are of the utmost urgency, since most clinical laboratories do not test genomovar status. The exclusion of genomovar III patients from pulmonary transplantation needs careful consideration. Such patients might feel that despite the potential outcome, transplantation is still an option to consider. However, when candidates with other B cepacia complex genomovar infections, or non-B cepacia infections, are likely to have better outcomes, transplantation in patients with genomovar III is hard to justify. Donor organ shortages result in a 40% death rate in patients with cystic fibrosis awaiting transplantation. Transplantation of patients infected with genomovar III has a number of effects including early death of the transplanted patient, waste of a lung from the donor, and another patient being denied transplantation. However, the Toronto group1 has reported a reduction in mortality of presumed genomovar III recipients by use of triple antibiotic regimens. Therefore, hope for these patients might reside in the synergistic antibacterial effect of multiple antibiotic regimens.5 1
2
3
4 5
Chaparro C, Maurer J, Gutierrez C, et al. Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation. Am J Respir Crit Care Med 2001; 163: 43–48. Mahenthiralingam E, Bischof J, Byrne SK, et al. DNA-based diagnostic approaches for the identification of Burkholderia cepacia complex, Burkholderia vietnamensis, Burkholderia multivorans, Burkholderia stabilis, and Burkholderia cepacia genomovars I and III. J Clin Microbiol 2000; 38: 3165–73. Mariencheck WI Jr, Palmer SM, Tapson VF, Davis RD. Survival following lung transplantation of cystic fibrosis patients colonized with Burkholderia cepacia. Am J Respir Crit Care Med 2000; 161: 720. Yankaskas JR, Mallory GB Jr. Lung transplantation in cystic fibrosis: consensus conference statement. Chest 1998; 113: 217–26. Aaron SD, Ferris W, Henry DA, Speert DP, MacDonald NE. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia. Am J Respir Crit Care Med 2000; 161: 1206–12.
Departments of Respiratory Medicine (A De Soyza MRCP, Prof P A Corris FRCP), Medical Microbiology (L Archer BSc, K Gould FRCPath), and Cardiopulmonary Transplantation (Prof J H Dark FRCS, Prof P A Corris), The Freeman Hospital, High Heaton, Newcastle-upon-Tyne NE7 7DN, UK; Departments of Bacteriology (A McDowell PhD) and Respiratory Medicine (S J Elborn FRCP), Belfast City Hospital, Belfast; and Cardiff School of Biosciences, Cardiff University, Cardiff (E Mahenthiralingam PhD) Correspondence to: Dr Anthony De-Soyza (e-mail: [email protected])
1781
For personal use. Only reproduce with permission from The Lancet Publishing Group.
enzyme immunoassay with baculovirus-based, recombinant VP2 protein (Biotrin, Dublin, Ireland) and calibrators (3·1, 6·25, 25, 50, and 100 IU) that allowed expression of results in IU. In non-immune individuals, the concentration of parvovirus-B19-specific IgG was usually lower than 5 IU, and seroconversion was assumed if it rose to more than 20 IU, although values exceeded 100 IU in most patients. Timing of infection was assumed to coincide with aplastic crises in those affected, and with the occurrence of abnormal haematology in patients with minor haematological change. In 43 patients without known haematological change, a window of seroconversion between the last negative and first positive sample was narrowed by assessment of further available samples within the window. Seven patients in whom the first positive sample showed IgM were assumed to have had infections within the preceding 3 months; in the remaining 36 patients, the event window had a median length of 61 weeks (IQR 40–143, range 19–280). These different methods of estimating timing of infection complicated assessment, but assumption that the event occurred at the midpoint in the interval window allowed us to use standard Kaplan-Meier methods; however, since this assumption could bias inferences and underestimate uncertainty, we also used a generalisation of the KaplanMeier estimate incorporating interval-censoring.4 Between June, 1973, and July, 2000, seroconversion occurred in 177 individuals, of whom 118 (67%) had clinical aplasia, 16 (9%) showed minor haematological change, and 43 (24%) were without known haematological change. Time to seroconversion by both Kaplan-Meier and Turnbull4 estimation were similar: 61% were affected by age 15 years and 70% by age 20 years (table 1). Only one patient with a clinically defined aplasia had no evidence of parvovirus B19 infection: a girl who became infected at age 9·3 years, who had a haemoglobin concentration of 24 g/L, zero reticulocytes, and who recovered normally after transfusion. She showed no evidence of parvovirus B19 IgG or IgM, and blood cultures were sterile. Haematological features in patients showing typical, minor, or no known haematological change are summarised in table 2. Assessed by normal regression, and after adjustment for baseline haemoglobin concentration, age at seroconversion, and sex, steady-state fetal haemoglobin was slightly higher in individuals with less haematological change during parvovirus B19 infection (p=0·03), but the number of ␣ globin genes had no effect. The arbitrary definition of aplastic crisis had a high predictive value: 118 of 119 clinically defined aplasias were associated with parvovirus B19 infection. This definition missed 16 patients with less characteristic haematological change and a further 43 individuals who, despite close monitoring, showed no known haematological change. Seroconversion in 61% of homozygous sickle-cell patients by 15 years, was similar to the 50% recorded among 11–15 year-olds in a British population,5 and is more consistent with clinical observations that aplastic crises in homozygous sickle-cell disease become uncommon after age 15 years. Virtually all clinically defined aplastic crises result from parvovirus B19 infection, but a third of infections do not manifest typical aplasia. After infection, immunity to further aplastic crises seems to be life-long and no recurrences occurred during 1859 patient-years of observation. The natural history of aplastic crisis is essentially benign since bone-marrow activity almost always resumes after 7–10 days aplasia, but deaths can result from extreme anaemia and from associated problems such as acute chest syndrome, nephrotic syndrome, and stroke. These features add urgency to the development of a human parvovirus vaccine.
1780
We thank Douglas Higgs (Weatherall Institute of Molecular Medicine, University of Oxford, UK) for the determination of ␣ globin gene number. 1
2 3
4 5
Serjeant GR, Topley JM, Mason K, at al. Outbreak of aplastic crises in sickle cell anaemia associated with parvovirus-like agent. Lancet 1981; 2: 595–97. Anderson MJ, Higgins PG, David LR, et al. Experimental parvoviral infection in humans. J Infect Dis 1985; 152: 257–65. Serjeant GR, Serjeant BE, Thomas P, Anderson MJ, Patou G, Pattison JR. Human parvovirus infection in homozygous sickle cell disease. Lancet 1993; 341: 1237–40. Turnbull BW. The empirical distribution function with arbitrary grouped, censored and truncated data. J R Stat Soc 1976; 38: 290–95. Brown KE. Human parvovirus B19 epidemiology and clinical manifestations. In: Parks WP, ed. Monographs in virology, vol 20. Basel: Karger, 1997: 42–60.
Sickle Cell Trust, 14 Milverton Crescent, Kingston 6, Jamaica (B E Serjeant FIBMS, Prof G R Serjeant MD); Sickle Cell Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston (I R Hambleton MSc); and Biotrin, County Dublin, Ireland (S Kerr PhD, C G Kilty PhD) Correspondence to: Prof Graham R Serjeant (e-mail: [email protected])
Burkholderia cepacia complex genomovars and pulmonary transplantation outcomes in patients with cystic fibrosis Anthony De Soyza, Andrew McDowell, Lynda Archer, John H Dark, Stuart J Elborn, Eshwar Mahenthiralingam, Kate Gould, Paul A Corris Burkholderia cepacia is a group of organisms that comprises seven genotypically distinct species (B cepacia genomovars I–VII), which are collectively known as the B cepacia complex. Preoperative infection with B cepacia is associated with a poor prognosis in lung transplant recipients with cystic fibrosis. Many centres do not, therefore, offer transplants to these individuals. Our aim was to ascertain whether or not post-transplant mortality is affected by pretransplant genomovar status. We studied archived isolates with PCR-based methods, and recorded excessive mortality in patients infected with B cepacia genomovar III, but not in those infected with other genomovars.
Lancet 2001; 358: 1780–81
Burkholderia cepacia causes pulmonary infection in 3–5% of patients with cystic fibrosis in UK and USA, although infection rates of 50% have been noted in some centres.1 B cepacia comprises seven genotypically distinct species, or genomovars, known as the B cepacia complex.2 Although all genomovars of this complex are capable of causing pulmonary infection in patients with cystic fibrosis, the most pathogenic are genomovar III and, to a lesser extent, genomovar II (B multivorans). Lung transplantation improves both the quantity and quality of life of patients with advanced cystic fibrosisassociated lung disease. However, lung transplantation outcomes are variable for patients colonised with B cepacia. Some studies have reported 1-year mortality rates of between 50% and 100%,1 however, survival rates greater than 75% have been noted.3 As a result of this potentially poor prognosis, many centres do not transplant individuals infected with B cepacia. We, however, do not deny individuals transplantation in the absence of other contraindications.4 We postulated that the disparity in posttransplant outcomes was dependent on the preoperative B cepacia complex genomovar responsible for infection.
THE LANCET • Vol 358 • November 24, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
RESEARCH LETTERS
Patient
Status post-transplant (days survived)
B cepacia complex genomovar
Antibiotic sensitivity
C-reactive protein (mg/L)
1 2 3 4 5 6 7 8 9 10 11
Alive (2400) Alive (1780) Alive (1125) Alive (274) Alive (156) Alive (80) Dead (10) Dead (27) Dead (31) Dead (35) Dead (36)
Unknown B multivorans B vietnamiensis B multivorans B vietnamiensis B multivorans Unknown B cepacia genomovar III B cepacia genomovar III B cepacia genomovar III B cepacia genomovar III
Unknown Multiresistant Multiresistant Multiresistant Panresistant Panresistant Multiresistant Panresistant Panresistant Panresistant Panresistant
180 Unknown Unknown 20 110 460 40 Unknown 680 250 30
White blood cell count (⫻1012/L) 11.5 11.8 11.2 10.5 12.1 15.0 20.6 23.3 13.3 14.0 10.9
Pretransplant temperature 36.8 37.2 37.1 36.5 36.1 36.8 37.2 36.5 37·0 37.6 37.7
Characteristics of pulmonary transplant recipients infected with Burkholderia cepacia complex
We reviewed our cystic fibrosis pulmonary transplant database, patient charts, and case notes. The immunosuppressive regimen used was similar to that previously described.1 Briefly, we made Clamshell incisions and prescribed prophylactic antibiotics according to the sensitivity of the bacterial isolates. If the isolate was pan-resistant,4 or unknown, 2 g aztreonam was given every 8 h for 2–7 days perioperatively. We assessed the clinical status of every patient immediately before the operation by measurement of bodymass index (BMI), core temperature, white cell count, and serum C-reactive protein concentration. We took samples of expectorated sputum during pretransplant assessment, immediately before surgery, and at post-transplant, and samples of postoperative bronchoalveolar lavage. We isolated B cepacia complex by selective culture, and identified them with the API20 NE phenotypic system (bioMerieux, Marcy l’Etoile, France). Antibiotic sensitivities were identified by disc diffusion. All pretransplant and post-transplant isolates were archived at ⳮ70°C pending PCR analysis,2 which was used to confirm that isolates were organisms of the B cepacia complex and to ascertain their genomovar status. We used Fisher’s exact test to measure post-transplant survival between patients who were and were not infected with B cepacia complex. 11 of 84 lung transplant recipients with cystic fibrosis had preoperative B cepacia complex infection (table). B cepacia complex organisms from nine of these individuals were successfully cultured from storage. We analysed 53 isolates, representing at least one pretransplant and day-of-transplant isolate and multiple post-transplant isolates from every patient. All isolates were identified as B cepacia by biochemical analysis. PCR-based analysis showed two patients were infected preoperatively with B vietnamiensis (genomovar V), three with B multivorans (genomovar II), and four with genomovar III. Immediate pretransplant and post-transplant genomovar status remained constant for every patient. Of the 11 patients with cystic fibrosis who were also infected with B cepacia complex, five died post-transplant because of progressive B cepacia related sepsis. Four of these patients had genomovar III infections. The genomovar infection in one patient who died was not identified; their archived isolates could not be cultured. All five patients were clinically unresponsive to cyclical antibiotics and thoracostomy drainage. B cepacia bacteraemia was found in four patients. The other six patients infected with B cepacia complex survived the early post-transplant period, and are making good progress. Archived samples from one survivor could not be cultured for genomovar designation. Of the five remaining patients, two were infected with B vietnamiensis (genomovar V) and three with B multivorans (genomovar II). The survival rates between genomovar III and non-genomovar III-infected patients differed significantly (100%; 95% CI 35–100; p=0·007). There were no clear differences between the B cepacia complex-infected survivor and non-survivor groups for BMI, core temperature, white cell count, and Creactive protein concentrations (table). The small numbers, however, limit analysis for potential confounding variables.
THE LANCET • Vol 358 • November 24, 2001
Our results show that patients with pretransplant genomavar III infections are at greater risk of death caused by B cepacia sepsis during the early postoperative period than those infected with B multivorans and B vietnamiensis, who have a good chance of surviving long-term post-transplant. The decision of some centres to place a moratorium on all patients with preoperative B cepacia infection might not, therefore, be justified. Further studies are needed to confirm our results before firm clinical conclusions can be drawn. Such studies are of the utmost urgency, since most clinical laboratories do not test genomovar status. The exclusion of genomovar III patients from pulmonary transplantation needs careful consideration. Such patients might feel that despite the potential outcome, transplantation is still an option to consider. However, when candidates with other B cepacia complex genomovar infections, or non-B cepacia infections, are likely to have better outcomes, transplantation in patients with genomovar III is hard to justify. Donor organ shortages result in a 40% death rate in patients with cystic fibrosis awaiting transplantation. Transplantation of patients infected with genomovar III has a number of effects including early death of the transplanted patient, waste of a lung from the donor, and another patient being denied transplantation. However, the Toronto group1 has reported a reduction in mortality of presumed genomovar III recipients by use of triple antibiotic regimens. Therefore, hope for these patients might reside in the synergistic antibacterial effect of multiple antibiotic regimens.5 1
2
3
4 5
Chaparro C, Maurer J, Gutierrez C, et al. Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation. Am J Respir Crit Care Med 2001; 163: 43–48. Mahenthiralingam E, Bischof J, Byrne SK, et al. DNA-based diagnostic approaches for the identification of Burkholderia cepacia complex, Burkholderia vietnamensis, Burkholderia multivorans, Burkholderia stabilis, and Burkholderia cepacia genomovars I and III. J Clin Microbiol 2000; 38: 3165–73. Mariencheck WI Jr, Palmer SM, Tapson VF, Davis RD. Survival following lung transplantation of cystic fibrosis patients colonized with Burkholderia cepacia. Am J Respir Crit Care Med 2000; 161: 720. Yankaskas JR, Mallory GB Jr. Lung transplantation in cystic fibrosis: consensus conference statement. Chest 1998; 113: 217–26. Aaron SD, Ferris W, Henry DA, Speert DP, MacDonald NE. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia. Am J Respir Crit Care Med 2000; 161: 1206–12.
Departments of Respiratory Medicine (A De Soyza MRCP, Prof P A Corris FRCP), Medical Microbiology (L Archer BSc, K Gould FRCPath), and Cardiopulmonary Transplantation (Prof J H Dark FRCS, Prof P A Corris), The Freeman Hospital, High Heaton, Newcastle-upon-Tyne NE7 7DN, UK; Departments of Bacteriology (A McDowell PhD) and Respiratory Medicine (S J Elborn FRCP), Belfast City Hospital, Belfast; and Cardiff School of Biosciences, Cardiff University, Cardiff (E Mahenthiralingam PhD) Correspondence to: Dr Anthony De-Soyza (e-mail: [email protected])
1781
For personal use. Only reproduce with permission from The Lancet Publishing Group.