Malignant Otitis Externa: A Novel Stratification Protocol for Predicting Treatment Outcomes.

OBJECTIVES: 1) Stratify malignant otitis externa into severe and nonsevere disease categories. 2) Predict treatment courses and outcomes based on this stratification. SETTING: Tertiary center. PATIENTS: Retrospective review 2004 to 2014; 28 patients. Inclusion criteria are a diagnosis by senior authors, radiographic evidence of disease, admission for intravenous antibiotics/debridement, minimum 1 year of follow-up. INTERVENTIONS: Severe group stratification if two or more of the following: cranial nerve VII palsy, fungal positive culture, relapse, surgery performed, major radiographic findings. All other patients stratified to nonsevere group. MAIN OUTCOME MEASURES: Cure, alive/refractory disease, death by disease, death by other cause. Secondary measures are antibiotic duration and number of disease-related admissions. RESULTS: Forty-three percent (12 of 28) and 57% (16 of 28) of patients stratified into the severe and nonsevere groups. The severe group had significantly more adverse disease-specific outcomes than the nonsevere group (7 of 12 versus 0 of 16; p = 0.002). Disease-specific mortality was 42% and 0% in the severe and nonsevere groups, respectively. The severe group had longer antibiotic courses (12.8 versus 6.9 wk; p = 0.01) and more disease-related admissions/relapses (1.6 versus 1, p < 0.001). Only four of 12 severe group patients achieved cure. All but two nonsevere patients achieved cure, with those two dying of other causes. CONCLUSION: A subgroup of malignant otitis externa may exist that is not as susceptible to parenteral antibiotics and local debridement. A combination of clinical and radiographic findings may be useful for stratifying patients into severe/nonsevere categories. Patients with severe disease may be more likely to die of their disease and have worse treatment courses such that additional surgical intervention may be indicated.

Detection of P. aeruginosa harboring bla CTX-M-2, bla GES-1 and bla GES-5, bla IMP-1 and bla SPM-1 causing infections in Brazilian tertiary-care hospital.

BACKGROUND: Nosocomial infections caused by Pseudomonas aeruginosa presenting resistance to beta-lactam drugs are one of the most challenging targets for antimicrobial therapy, leading to substantial increase in mortality rates in hospitals worldwide. In this context, P. aeruginosa harboring acquired mechanisms of resistance, such as production of metallo-beta-lactamase (MBLs) and extended-spectrum beta-lactamases (ESBLs) have the highest clinical impact. Hence, this study was designed to investigate the presence of genes codifying for MBLs and ESBLs among carbapenem resistant P. aeruginosa isolated in a Brazilian 720-bed teaching tertiary care hospital. METHODS: Fifty-six carbapenem-resistant P. aeruginosa strains were evaluated for the presence of MBL and ESBL genes. Strains presenting MBL and/or ESBL genes were submitted to pulsed-field gel electrophoresis for genetic similarity evaluation. RESULTS: Despite the carbapenem resistance, genes for MBLs (blaSPM-1 or blaIMP-1) were detected in only 26.7% of isolates. Genes encoding ESBLs were detected in 23.2% of isolates. The blaCTX-M-2 was the most prevalent ESBL gene (19.6%), followed by blaGES-1 and blaGES-5 detected in one isolate each. In all isolates presenting MBL phenotype by double-disc synergy test (DDST), the blaSPM-1 or blaIMP-1 genes were detected. In addition, blaIMP-1 was also detected in three isolates which did not display any MBL phenotype. These isolates also presented the blaCTX-M-2 gene. The co-existence of blaCTX-M-2 with blaIMP-1 is presently reported for the first time, as like as co-existence of blaGES-1 with blaIMP-1. CONCLUSIONS: In this study MBLs production was not the major mechanism of resistance to carbapenems, suggesting the occurrence of multidrug efflux pumps, reduction in porin channels and production of other beta-lactamases. The detection of blaCTX-M-2,blaGES-1 and blaGES-5 reflects the recent emergence of ESBLs among antimicrobial resistant P. aeruginosa and the extraordinary ability presented by this pathogen to acquire multiple resistance mechanisms. These findings raise the concern about the future of antimicrobial therapy and the capability of clinical laboratories to detect resistant strains, since simultaneous production of MBLs and ESBLs is known to promote further complexity in phenotypic detection. Occurrence of intra-hospital clonal dissemination enhances the necessity of better observance of infection control practices.

Fatal Pseudomonas aeruginosa pneumonia in a previously healthy woman was most likely associated with a contaminated hot tub.

Community-acquired pneumonia due to Pseudomonas aeruginosa in previously healthy individuals is a rare disease that is associated with high fatality. On 14 February 2010 a previously healthy 49-year-old woman presented to an emergency room with signs and symptoms of pneumonia, 2 days after returning from a spa holiday in a wellness hotel. Blood cultures and respiratory specimens grew P. aeruginosa. Despite adequate antimicrobial therapy, the patient died of septic multiorgan failure on day nine of hospitalization. On February 26, nine water samples were taken from the hotel facilities used by the patient: In the hot tub sample 37,000 colony-forming units of P. aeruginosa/100 ml were detected. Two of five individual colonies from the primary plate used for this hot tub water sample were found to be genetically closely related to the patient's isolates. Results from PFGE, AFLP and MLST analysis allowed the two lung isolates gained at autopsy and the whirlpool bathtub isolates to be allocated into one cluster. The patient most likely acquired P. aeruginosa from the contaminated water in the hotel's hot tub. The detection of P. aeruginosa in high numbers in a hot tub indicates massive biofilm formation in the bath circulation and severe deficiencies in hygienic maintenance. The increasing popularity of hot tubs in hotels and private homes demands increased awareness about potential health risks associated with deficient hygienic maintenance.

Do New Zealand children with non-cystic fibrosis bronchiectasis show disease progression?

BACKGROUND: There is minimal literature available on the long-term outcome of pediatric non-cystic fibrosis (CF) bronchiectasis. AIM: To document 5-year outcomes of children with chest computerized tomography (CT) scan diagnosed bronchiectasis from a tertiary New Zealand (NZ) respiratory clinic. METHODS: Review of a clinical database identified 91 children. Demographics, clinical data, lung function, chest X-ray (CXR), sputum, presumed etiology, admission data, and the NZ deprivation index (NZDep) were collected. Univariate and multivariate regression were used to correlate clinical findings with lung function data and CXR scores using the Brasfield Scoring System. RESULTS: Of the 91 children, 53 (59%) were Pacific Island, 22 (24%) Maori, 14 (15%) European, and 2 (2%) Other. The median follow-up period was 6.7 years (range 5.0-15.3 years) and median age at diagnosis was 7.3 years (range 11 months-16 years). Lung function data (n = 64) showed a mean decline of -1.6% predicted/year. In 30 children lung function declined (mean FEV(1) -4.4% predicted/year, range 1-17%), remained stable in 13 and improved in 21 children (mean FEV(1) of +3% predicted/year, range 1-15%). Reduced lung function was associated with male gender, chronic Haemophilus influenzae infection, longevity of disease, and Maori and Pacific Island ethnicity. There was a significant correlation with FEV(1) and CXR score at beginning (n = 47, r = 0.45, P = 0.001) and end (n = 26, r = 0.59, P = 0.002) of the follow-up period. The only variable consistently related to CXR score was chronic Haemophilus influenzae infection occurring in 27 (30%) (r(2) = 0.52, P = <0.0001). Only four children were chronically infected with Pseudomonas species. Six children died. CONCLUSION: In our experience despite management in a tertiary multidisciplinary bronchiectasis clinic, progression of lung disease continues in a group of children and young adults.

Early eradication of Pseudomonas aeruginosa in patients with cystic fibrosis.

Pseudomonas aeruginosa (Pa) is the predominant organism infecting the airways of patients with cystic fibrosis (CF). This organism has an armamentarium of survival mechanisms that allows it to survive in the CF airway. Since colonization and chronic infection with Pa is associated with poorer lung function and increased morbidity and mortality, therapies that can prevent infection could significantly improve the lives of patients with CF. Numerous studies have examined the effects of treatment on the eradication of Pa as a means to ameliorate disease. This article outlines the pathophysiology and clinical implication of Pa acquisition, and reviews the existing treatment regimens aimed at early eradication of Pa in patients with CF.

Pseudomonas aeruginosa in chronic obstructive pulmonary disease.

RATIONALE: Pseudomonas aeruginosa is isolated from adults with chronic obstructive pulmonary disease (COPD) in cross-sectional studies. However, patterns of carriage and the role of P. aeruginosa in COPD are unknown. OBJECTIVES: To elucidate carriage patterns, phenotypes of strains, clinical manifestations, and the antibody response to P. aeruginosa in COPD. METHODS: A prospective study of adults with COPD was conducted. Isolates of P. aeruginosa were subjected to genotypic and phenotypic analysis. Sputum samples were studied for P. aeruginosa DNA, and immune responses were assayed. MEASUREMENTS AND MAIN RESULTS: We analyzed longitudinal clinical data, sputum cultures, pulsed-field gel electrophoresis of bacterial DNA, polymerase chain reaction of sputum, and immunoblot assays of serum. Fifty-seven episodes of acquisition of strains of P. aeruginosa were observed in 39 of 126 patients over 10 years. Acquisition of a new strain was associated with exacerbation. Thirty-one episodes of carriage were followed by clearance of the strain; 16 were of short (<1 mo) duration. Thirteen strains demonstrated persistence, and 13 strains were of indeterminate duration. Six strains were mucoid and were more likely to persist than nonmucoid strains (P = 0.005). Antibody responses developed in 53.8% of persistent carriage and in only 9.7% of short-term carriage episodes (P = 0.003). Antibiotics did not account for clearance. CONCLUSIONS: Two distinct patterns of carriage by P. aeruginosa were observed: (1) short-term colonization followed by clearance and (2) long-term persistence. Mucoid strains showed persistence. Acquisition of P. aeruginosa is associated with the occurrence of an exacerbation. Serum antibody responses do not mediate clearance of P. aeruginosa.

Transmission of Pseudomonas aeruginosa in children with cystic fibrosis attending summer camps in The Netherlands.

BACKGROUND: Cross-infection of Pseudomonas aeruginosa has been reported to occur at holiday camps for children with Cystic Fibrosis (CF) with varying frequency. The study aimed to establish the degree of transmission resulting in subsequent infection of P. aeruginosa among CF children (n=80) attending holiday camps in The Netherlands. METHODS: The study was performed in the summer of 2001 in four camps organised simultaneously at different locations. Sputum was collected on day 1 of the holiday, and three and six months later. Different morphotypes of P. aeruginosa from sputum were genotyped by AFLP analysis. Criteria were defined for the degree of evidence of transmission. RESULTS: There were 18 cases possible, 2 cases of probable transmission and 1 case of highly probable transmission. Two predominant types of P. aeruginosa were found (types 18 and 23). Type 18 was already prevalent on day 1 mostly in younger children and was involved in eleven cases of transmission; type 23 was involved in six cases of transmission among older children. CONCLUSIONS: There was a considerable risk of transmission of P. aeruginosa during holiday camps for CF children in The Netherlands. Two genotypes of P. aeruginosa appeared to be easily transmissible, one of which seemed common in the Dutch CF population.

DNA microarray for genotyping multidrug-resistant Pseudomonas aeruginosa clinical isolates.

The management of infections with multidrug-resistant Pseudomonas aeruginosa needs fast and reliable methods of antibiotic susceptibility testing for a therapy improvement. For this purpose, we developed a DNA microarray for genotyping antibiotic resistance and a few virulence factors. The array covers mutations in the efflux regulators mexR, nfxB, mexT, gyrase gyrA, and parC, as well as plasmid-encoded vim, imp, oxa, aph, aac, and aad genes, and virulence-associated mucA and exoU, exoT, and exoS genes, respectively. The whole procedure can be performed in less than 5 h and consists of DNA isolation, target gene amplification, fluorescence labeling, fragmentation, and array hybridization. Concerning the genotype-phenotype comparison in the test collection, the coverage of relevant resistance determinants for antibiotics used in a calculated therapy of critical ill patients was 87.8%.

Comparison of antimicrobial cycling and mixing strategies in two medical intensive care units.

OBJECTIVE: To compare a mixing vs. a cycling strategy of use of anti-Pseudomonas antibiotics on the acquisition of resistant Gram-negative bacilli in the critical care setting. DESIGN: Prospective, open, comparative study of two strategies of antibiotic use. SETTING: Two medical intensive care units of a university hospital. PATIENTS: A total of 346 patients admitted for >or=48 hrs to two separate medical intensive care units during an 8-month period. INTERVENTIONS: Patients, who according to the attending physician's judgment required an anti-Pseudomonas regimen, were assigned to receive cefepime/ceftazidime, ciprofloxacin, a carbapemen, or piperacillin-tazobactam in this order. "Cycling" was accomplished by prescribing one of these antibiotics during 1 month each. "Mixing" was accomplished by using the same order of antibiotic administration on consecutive patients. Interventions were carried out during two successive 4-month periods, starting with mixing in one unit and cycling in the other. MEASUREMENTS AND MAIN RESULTS: Swabbing of nares, pharynx, and rectum and culture of respiratory secretions were obtained thrice weekly. The main outcome variable was the proportion of patients acquiring enteric or nonfermentative Gram-negative bacilli resistant to the antibiotics under intervention. The scheduled cycling of antibiotics was only partially successful. Although the expected antibiotic was the most prevalent anti-Pseudomonas agent used within the corresponding period, it never accounted for >45% of all anti-Pseudomonas antimicrobials administered. During mixing, a significantly higher proportion of patients acquired a strain of Pseudomonas aeruginosa resistant to cefepime (9% vs. 3%, p = .01), and there was a trend toward a more frequent acquisition of resistance to ceftazidime (p = .06), imipenem (p = .06), and meropenem (p = .07). No differences in the rate of acquisition of potentially resistant Gram-negative bacilli or incidence of intensive care unit-acquired infections and infections due to particular organisms were observed. CONCLUSIONS: In critically ill medical patients, a strategy of monthly rotation of anti-Pseudomonas beta-lactams and ciprofloxacin may perform better than a strategy of mixing in the acquisition of P. aeruginosa resistant to selected beta-lactams.

Phenotypic and genotypic characteristics of Pseudomonas aeruginosa strains isolated from hospitals in the north-west region of Poland.

A total of 90 Pseudomonas aeruginosa strains isolated from 4 hospitals in the west-north region of Poland were studied by arbitrarily primed polymerase chain reaction (AP-PCR). AP-PCR results revealed the presence of 11 main groups of patterns (A-K) and 5 unique patterns among isolates. Generally, they were characterized by high resistance to antibiotics tested and significant differences in serogroups and types of growth on Cetrimide Agar medium. It was observed that clonally related strains were isolated from patients within the same ward, among different wards as well as in distant hospitals.

Characterization of Pseudomonas aeruginosa isolated from chronically infected children with cystic fibrosis in India.

BACKGROUND: Pseudomonas aeruginosa is the leading cause of morbidity and mortality in patients with cystic fibrosis (CF). With chronicity of infection, the organism resides as a biofilm, shows multi-drug resistance, diversifies its colony morphology and becomes auxotrophic. The patients have been found to be colonized with multiple genotypes. The present work was carried out to characterize P. aeruginosa isolated from children with cystic fibrosis using phenotypic and genotypic methods. RESULTS: We studied 56 patients with CF attending the Pediatric Chest clinic at All India Institute of Medical Sciences, New Delhi, India during August 1998-August 2001. These patients were regularly followed up at the clinic. Out of 56 patients, 27 were culture positive for P. aeruginosa where 8 were chronically infected (Group1) and 19 were intermittently colonized with the organism (Group2). Patients under Group1 had significantly higher rates of hospitalization, death and colonization with different colony morphotypes (p < 0.05). The isolates from Group1 patients were the positive producers of extended spectrum beta lactamase. A total of 5 auxotrophs were recovered from 2 patients where one was chronically infected with P. aeruginosa and the other was a recently enrolled patient. The auxotrophs had the specific requirement for methionine and arginine. Molecular typing revealed 33 ERIC-PCR (E1-E33) and 5 PCR-ribotyping (P1-P5) patterns. By ERIC-PCR, 4 patients were colonized with 2-4 genotypes and the remaining 23 patients were colonized with the single genotype. CONCLUSION: With chronicity of infection, P. aeruginosa becomes multidrug resistant, diversifies its colony morphology, acquires mucoidity and shows auxotrophy for amino acids. The chronically infected patients can be colonized with multiple genotypes. Thus in a particular clinical set up, high index of suspicion should be there for diagnosis of CF patients so as to prevent the delay in diagnosis and management of CF patients.

Impact of severity of illness bias and control group misclassification bias in case-control studies of antimicrobial-resistant organisms.

BACKGROUND: Case-control studies often analyze risk factors for antibiotic resistance. Recently published articles have illustrated that randomly selected control-patients may be preferable to those with the susceptible phenotype of the organism. A possible methodologic problem with randomly selected control-patients is potential bias due to control group misclassification. This occurs if some control-patients did not have clinical cultures performed and thus might have been unidentified case-patients. If this bias exists, these studies might be expected to report lower odds ratios (ORs) because control-patients would be more like case-patients. OBJECTIVE: To analyze potential biases that might arise due to control group misclassification and potentially larger selection biases that may be introduced if control-patients are required to have at least one clinical culture. PATIENTS: One hundred twenty case-patients, 770 control-patients in group 1, and 510 control-patients in group 2. METHODS: Two case-control studies. Case-patients had clinical cultures positive for imipenem-resistant Pseudomonas aeruginosa. The first group of control-patients were random. The second group of control-patients were identical to those in group 1 except being required to have at least one clinical culture. RESULTS: Univariate analyses showed higher ORs for case-patients versus control-patients in group 1 (imipenem [OR, 12.5], piperacillin-tazobactam [OR, 3.7], and vancomycin [OR, 4.7]) as compared with case-patients versus control-patients in group 2 (imipenem [OR, 8.0], piperacillin-tazobactam [OR, 2.5], and vancomycin [OR, 3.0]). CONCLUSION: Requiring control-patients to have at least one clinical culture introduces a selection bias likely because it eliminates patients with less severe illness.

Long-term results of multiple-stage treatment for posttraumatic osteomyelitis of the tibia.

BACKGROUND: The treatment of posttraumatic osteomyelitis of the tibia requires meticulous debridement and adequate soft tissue coverage. At our institution, we perform a staged procedure consisting of surgical debridement followed by muscle coverage. If necessary, implantation of a cancellous iliac bone graft was always performed as a three-stage treatment. METHODS: We performed a retrospective analysis of 47 patients treated for posttraumatic osteomyelitis of the tibia between 1987 and 1998. RESULTS: Twenty-two patients originally had a Gustilo grade III fracture, 21 patients had a Gustilo grade I or II or closed fracture, the Gustilo grade was not known for 2 patients, and 2 patients had no fracture. Using the Cierny-Mader classification, most patients had a localized osteomyelitis. To cover the debrided area, 20 pedicled muscle transfers and 28 microvascular free flaps were used; one patient had two localizations of osteomyelitis (both proximal and distal) and received two muscle flaps. Flap failure was 8% and was successfully treated by additional flap coverage in two cases; one was closed by a split skin graft and one was closed by secundum. Twenty-six patients received a cancellous bone graft. During an average follow-up of 94 months, 9% had a recurrence of osteomyelitis for which additional surgical interventions were necessary. Finally, all the infections were eventually cured. CONCLUSION: Our staged surgery proved to be an excellent method of treating osteomyelitis after open or closed fractures of the tibia.

[Should we screen for colonization to control the spread of multidrug resistant bacteria?]. / Quelles stratégies découlent de la surveillance des bactéries multirésistantes aux antibiotiques afin de mieux maîtriser leur diffusion?

Should we screen for colonization to control the spread of multidrug-resistant bacteria? A multidrug-resistant bacteria surveillance program was performed in 1999 at Laënnec Hospital (Nantes, France). After a 3-year period, the results permit us to determine the strategy to strengthen their spread. In 2001, Staphylococcus aureus resistant to methicillin represented 45% of the 202 multidrug-resistant bacteria isolated. The global incidence rate per 100 admissions remained stable between 1999 and 2001 (0.42%), but those of infections acquired in our institution decreased significantly from 0.27% in 1999 to 0.18% in 2001 (P < 0.05), particularly in medical care units (P < 0.04). In spite of this surveillance program and hygiene trainings, the global incidence remained stable during the study period, even if our action contributed to decrease the incidence of S. aureus resistant to methicillin acquired in our institution. Isolation precautions and screening for colonization policy in intensive care units are not sufficient to control the spread of MRB at hospital level. They should be strengthened by procedures for the transfer of infected or colonized patients and by antibiotic use control.

Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

BACKGROUND: Patients were defined each successive month as either 'chronic' when more than 50% of the preceding 12 months were PA culture positive, 'intermittent' when < or =50% of the preceding 12 months were PA culture positive, 'free of PA', with no growth of PA for the previous 12 months, having previously been PA culture positive, or 'never infected', when PA had never been cultured. METHODS: Cross-sectional analysis of 146 children attending the Leeds Regional Cystic Fibrosis Centre was performed to assess relationship between the new definition and clinical scores and investigations. The response variable was regressed on age and sex and the residuals analysed using the Kruskal-Wallis test. RESULTS: The 'chronic' group (18% of patients) had significantly worse Shwachman-Kulczycki (SK) and Northern chest X-ray scores, and % predicted FEV(1) values than the 'free' (28%) or 'never' (20%) categories (P<0.004). The 'intermittent' group (34%) had a significantly higher SK score than the 'chronic' group (P<0.0001), and a significantly lower % predicted FEV(1) value than the 'free' or 'never' groups (P<0.0003). 'Chronic' patients were significantly associated with a positive, and 'never' patients with a negative, PA antibody result (P<0.001). CONCLUSIONS: The validity and importance of identifying these four subgroups is demonstrated. Previous definitions may over-estimate the prevalence of chronic infection.