Correlation Between Electrocochleographic Changes During Surgery and Hearing Outcome in Cochlear Implant Recipients: A Case Report and Systematic Review of the Literature.

OBJECTIVE: To determine the correlation between intraoperative changes of electrocochleography (ECochG) responses and traumatic cochlear implant insertions as well as postoperative hearing loss. METHODS: ECochG, radiological, and audiological data were collected prospectively in a cochlear implant recipient with otosclerosis and assumed cochlear trauma during electrode insertion. A systematic review was conducted within PubMed-NCBI, EMBASE, and the Cochrane Library using the terms "Cochlear implant" and "Electrocochleography." Original studies that evaluated intraoperative ECochG responses and postoperative hearing loss were selected and analyzed. RESULTS: The case report revealed a drop of intra- and extracochlear ECochG signals during electrode insertion. The postoperative computed tomography scan suggested a scalar dislocation. There was no measurable hearing 4 weeks after surgery. Within the database search, nine articles met the inclusion criteria. All were case series reports (range from 2 to 36 subjects) with a total of 173 subjects. Due to the heterogeneous data, a meta-analysis was unfeasible. CONCLUSIONS: In concordance with some findings in the literature, the presented case report suggests that a drop of intra- and extracochlear ECochG signals during the insertion of the electrode array is associated with cochlear trauma and postoperative hearing loss in some cases. However, the literature is inconclusive regarding the correlation between intraoperative changes of the ECochG signals and postoperative hearing preservation. More studies investigating the correlation are needed to provide sufficient data.

Robotic single-site versus multiport laparoscopic cholecystectomy: a case-matched analysis of short- and long-term costs.

BACKGROUND: Multiport laparoscopy is the gold-standard approach for cholecystectomy, and single-port laparoscopy has been developed to further reduce its invasiveness. A specific robotic single-port platform (da Vinci single-site, Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2011, which could technically facilitate single-site cholecystectomy. Current data show its feasibility; however, detailed short- and long-term analyses of costs and comparisons relative to multiport laparoscopy are not available to date. METHODS: Patients who underwent robotic single-site cholecystectomy for benign, clinically noninflammatory disease between 2011 and 2015 were matched for disease, age, gender, BMI, ASA classification, diagnosis, and elapsed year of surgery to a cohort of multiport cholecystectomies. Demographic, perioperative, and long-term data were collected retrospectively and analyzed. Perioperative and long-term costs including re-operations due to the primary procedure until February 2017 were compared across both cohorts. RESULTS: 99 patients who underwent robotic single-site cholecystectomy were matched to 99 patients with multiport cholecystectomy. A higher rate of outpatient procedures in the robotic cohort (31.3 vs. 17.2%, p = 0.0305) was found, and demographic parameters and perioperative clinical outcomes were similar. Perioperative costs were significantly higher for the robotic single-site patients (6158.0 vs. 4288.0 USD, p < 0.0001). With similar follow-up times of 59.0 and 58.9 months, respectively (p = 0.9552), significantly more patients of the robotic Single-Site cohort underwent follow-up surgery (7.1 vs. 0.0%, p = 0.0140), and follow-up costs were significantly higher for the robotic cohort (694.7 vs. 0.0 USD, p = 0.0145). CONCLUSION: With similar early postoperative clinical results and a higher rate of re-operations, perioperative and long-term costs are significantly higher with robotic Single-Site cholecystectomy compared with multiport cholecystectomy. Considering the unclear clinical value of robotic single-site cholecystectomy and the significant short- and long-term costs, a call for further research and a debate as to who should bear the costs beyond the ones of the gold-standard treatment appear reasonable.

Robotic Gastric Bypass Surgery in the Swiss Health Care System: Analysis of Hospital Costs and Reimbursement.

BACKGROUND: Robotic technology shows some promising early outcomes indicating potentially improved outcomes particularly for challenging bariatric procedures. Still, health care providers face significant clinical and economic challenges when introducing innovations. METHODS: Prospectively derived administrative cost data of patients who were coded with a primary diagnosis of obesity (ICD-10 code E.66.X), a procedure of gastric bypass surgery (CHOP code 44.3), and a robotic identifier (CHOP codes 00.90.50 or 00.39) during the years 2012 to 2015 was analyzed and compared to the triggered reimbursement for this patient cohort. RESULTS: A total of 348 patients were identified. The mean number of diagnoses was 2.7 and the mean length of stay was 5.9 days. The overall mean cost per patients was Swiss Francs (CHF) from 2012 to 2014 that was 21,527, with a mean reimbursement of CHF 24,917. Cost of the surgery in 2015 was comparable to the previous years with CHF 22,550.0 (p = 0.6618), but reimbursement decreased significantly to CHF 20,499.0 (0.0001). CONCLUSIONS: The average cost for robotic gastric bypass surgery fell well below the average reimbursement within the Swiss DRG system between 2012 and 2014, and this robotic procedure was a DRG winner for that period. However, the Swiss DRG system has matured over the years with a significant decrease resulting in a deficit for robotic gastric bypass surgery in 2015. This stipulates a discussion as to how health care providers should continue offering robotic gastric bypass surgery, particularly in the light of developing clinical evidence.

Associations of diabetes mellitus with orthopaedic infections.

BACKGROUND: Clinical experience suggests that a high proportion of orthopaedic infections occur in persons with diabetes. METHODS: We reviewed several databases of adult patients hospitalized for orthopaedic infections at Geneva University Hospitals from 2004 to 2014 and retrieved 2740 episodes of infection. RESULTS: Overall, diabetes was noted in the medical record for 659 (24%) of these cases. The patients with, compared with those without, diabetes had more than five times more foot infections (274/659 [42%] vs 155/2081 [7%]; p < 0.01) and a significantly higher serum C-reactive protein level at admission (median 96 vs 70 mg/L; p < 0.01). Diabetic patients were older (median 67 vs 52 years; p < 0.01), more often male (471 [71%] vs 1398 [67%]; p = 0.04), and had more frequent polymicrobial infections (219 [37%] vs 353 [19%]; p < 0.01), including more gram-negative non-fermenting rods (90 [15%] vs 168 [9%]; p < 0.01). Excluding foot infections from these analyses did not change the statistically significant differences. Diabetes was present in 17% of all infected orthopaedic patients without foot involvement. In Geneva canton, the overall prevalence of diabetes is estimated at 5.1%, while we have found that the prevalence is 13% in our hospitalized adults. CONCLUSIONS: Diabetes is present in 24% of all adult patients hospitalized for surgery for an orthopaedic infection, a prevalence that is several times higher than for the general population and twice as high as that for the population of hospitalized patients. Compared with non-diabetics, patients with diabetes have significantly more infections that are polymicrobial, including gram-negative non-fermenting rods.

Are there clinical variables determining antibiotic prophylaxis-susceptible versus resistant infection in open fractures?

PURPOSE: In Gustilo grade III open fractures, it remains unknown which demographic or clinical features may be associated with an infection resistant to the administered prophylactic agent, compared to one that is susceptible. METHODS: This was a retrospective case-control study on patients hospitalized from 2004 to 2009. RESULTS: We identified 310 patients with Gustilo-III open fractures, 36 (12%) of which became infected after a median of ten days. In 26 (72%) of the episodes the pathogen was susceptible to the prophylactic antibiotic agent prescribed upon admission, while in the other ten it was resistant. All antibiotic prophylaxis was intravenous; the median duration of treatment was three days and the median delay between trauma and surgery was one day. In multivariate analysis adjusting for case-mix, only Gustilo-grade-IIIc fractures (vascular lesions) showed tendency to be infected with resistant pathogens (odds ratio 10; 95% confidence interval 1.0-10; p = 0.058). There were no significant differences between cases caused by antibiotic resistant and susceptible pathogen cases in patient's sex, presence of immune suppression, duration and choice of antibiotic prophylaxis, choice of surgical technique or materials, time delay until surgery, use of bone reaming, fracture localization, or presence of compartment syndrome. CONCLUSION: We were unable to identify any specific clinical parameters associated with infection with antibiotic resistant pathogens in Gustilo-grade III open fractures, other than the severity of the fracture itself. More research is needed to identify patients who might benefit from a broader-spectrum antibiotic prophylaxis.

Burden of bloodstream infection caused by extended-spectrum ß-lactamase-producing enterobacteriaceae determined using multistate modeling at a Swiss University Hospital and a nationwide predictive model.

OBJECTIVE: To obtain an unbiased estimate of the excess hospital length of stay (LOS) and cost attributable to extended-spectrum ß-lactamase (ESBL) positivity in bloodstream infections (BSIs) due to Enterobacteriaceae. DESIGN: Retrospective cohort study. SETTING: A 2,200-bed academic medical center in Geneva, Switzerland. PATIENTS: Patients admitted during 2009. METHODS: We used multistate modeling and Cox proportional hazards models to determine the excess LOS and adjusted end-of-LOS hazard ratio (HR) for ESBL-positive and ESBL-negative BSI. We estimated economic burden as the product of excess LOS and average bed-day cost. Patient-level accounting data provided a complementary analysis of economic burden. A predictive model was fitted to national surveillance data. RESULTS: Thirty ESBL-positive and 96 ESBL-negative BSI cases were included. The excess LOS attributable to ESBL-positive and ESBL-negative BSI was 9.4 (95% confidence interval [CI], 0.4-18.4) and 2.6 (95% CI, 0.7-5.9) days, respectively. ESBL positivity was therefore associated with 6.8 excess days and CHF 9,473 per BSI. The adjusted end-of-LOS HRs for ESBL-positive and ESBL-negative BSI were 0.62 (95% CI, 0.43-0.89) and 0.90 (95% CI, 0.74-1.10), respectively. After reimbursement, the average financial loss per acute care episode in ESBL-positive BSI, ESBL-negative BSI, and control cohorts was CHF 48,674, 48,131, and 13,532, respectively. Our predictive model estimated that the nationwide cost of third-generation cephalosporin resistance would increase from CHF 2,084,000 in 2010 to CHF 3,526,000 in 2015. CONCLUSIONS: This is the first hospital-wide analysis of excess LOS attributable to ESBL positivity determined using multistate modeling to avoid time-dependent bias. These results may inform health-economic evaluations of interventions targeting ESBL control.

Short parenteral antibiotic treatment for adult septic arthritis after successful drainage.

OBJECTIVES: To assess the risk factors for recurrence of septic arthritis with an emphasis on the duration of antibiotic treatment, to gather data for a prospective study on an optimized antibiotic treatment in adults with septic arthritis. METHODS: This was a retrospective single-center study conducted for the period 1996-2008. RESULTS: A total of 169 episodes of septic arthritis in 157 adult patients (median age 63 years; 65 females) were included. In 21 episodes (21/169, 12%), arthritis recurred after the end of antibiotic treatment. Multivariate analysis showed that Gram-negative infection (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.4-25.3), immune suppression (OR 5.3, 95% CI 1.3-22.0), and lack of surgical intervention were associated with recurrence. The size of the infected joint, the number of surgical drainages (OR 1.3, 95% CI 1.0-1.7), arthrotomy vs. arthroscopic drainage (OR 0.5, 95% CI 0.2-1.8), duration of antibiotic therapy (OR 1.0, 95% CI 0.95-1.05), and duration of intravenous antibiotic therapy (OR 1.0, 95% CI 1.0-1.0) were not. Seven days of intravenous therapy had the same success rate as 8-21 days (OR 0.4, 95% CI 0.1-1.7) and >21 days (OR 1.1, 95% CI 0.4-3.1). Fourteen days or less of total antibiotic treatment had the same outcome as 15-28 days (OR 0.4, 95% CI 0.1-2.3) or >28 days (OR 0.4, 95% CI 0.1-1.6). CONCLUSIONS: In this retrospective study of adults with septic arthritis, the duration of antibiotic therapy, or an early switch from intravenous to oral administration, did not statistically influence the risk of recurrence. Due to study limitations, the data cannot be used directly for antibiotic therapy recommendations for septic arthritis. Prospective randomized trials are warranted to optimize the antibiotic treatment of septic arthritis.

The CASSANDRE Project: automated alerts for optimal coding of diagnosis and interventions.

As of 1 January 2012,all Swiss hospitals have had to charge acute somatic care hospitalization according to the Swiss disease related group (DRG) System. In this system, hospital bills are based on the discharge summaries. Coders analyze these in order to identify diagnostic and interventional codes. These codes are used by the system grouper to determine a specific DRG code and cost-weight. The amount to be charged per episode is based on this cost-weight. Since acute care billing relies on discharge summaries and knowing that these are incomplete, our aim was to inprove the completeness of these documents by automatically detecting pathologies that should have been coded and charged. We also aimed to help improve the selection of the main diagnosis. We have implemented algorithms for the automatic detection of pathologies that directly inform the coders whilst by-passing the physician. Final validation of the new pathologies remains with the physician. Our results are very encouraging from a financial point of view.

Should the methicillin-resistant Staphylococcus aureus carriage status be used as a guide to treatment for skin and soft tissue infections?

OBJECTIVE: Previous skin carriage of methicillin-resistant Staphylococcus aureus (MRSA) leads frequently to empiric antibiotic MRSA coverage for skin & soft tissue infections. METHODS: Retrospective cohort study of orthopaedic patients hospitalized at Geneva University Hospitals (MRSA prevalence; 30%); community-acquired MRSA excluded. RESULTS: A total of 378 skin and soft tissue infections in 346 patients were retrieved. Overall cure was achieved in 330 episodes (87%) after a median antibiotic administration of 15 days. Among all episodes, 102 revealed a positive current MRSA status (during 2 weeks preceding infection; 27%) and 70 (19%) were MRSA carriers in the past. Sensitivity, specificity, positive and negative predictive values of current MRSA skin carriage to predict abscesses due to MRSA were 0.68, 0.77, 0.19, and 0.97, respectively. Fifty-four current MRSA carriers (54/102, 53%) and 30 past carriers (43%) were successfully treated with a non-MRSA antibiotic agent. In multivariate Cox regression analysis, anti-MRSA coverage (hazard ratio 1.2, 95%CI 0.5-2.8) and duration of antibiotic therapy (HR 1.0, 95%CI 0.96-1.02) did not influence treatment failure among patients with positive MRSA carriage. CONCLUSIONS: Current or past HA-MRSA skin carriage poorly predicts the need for anti-MRSA coverage for the antibiotic treatment of skin and soft tissue infections in hospitalized orthopaedic patients.

Outcome of treated and untreated asymptomatic bacteriuria in renal transplant recipients.

BACKGROUND: No guidelines exist concerning treatment of asymptomatic bacteriuria in renal transplant recipients (RTR). Because of scarce clinical symptoms and fear of complications, such episodes are frequently treated based on subjective criteria without clear clinical benefit, with the risk of selecting resistant pathogens. METHODS: We retrospectively analysed the outcome of 334 asymptomatic Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) bacteriuria that occurred in 77 RTR later than 1 month post-transplantation. We distinguished: Type I, high-grade bacteriuria with pyuria; Type II, high-grade bacteriuria without pyuria; Type III, low-grade bacteriuria with pyuria and Type IV, low-grade bacteriuria without pyuria. RESULTS: None of the 334 episodes was followed by acute rejection or chronic pyelonephritis. One hundred and one (30%) episodes were treated [32 (62%) Type I, 38 (45%) Type II, 13 (36%) Type III and 18 (11%) Type IV]. Evolution to symptomatic urinary tract infection (UTI) was similar between treated and untreated episodes (0/101 versus 4/233, P = 0.32). The four UTI resolved favourably without further complication upon treatment. Persistent asymptomatic bacteriuria occurred in 45 (46%) treated episodes (2 Type I, 27 Type II, 8 Type III and 9 Type IV), with selection of resistant pathogen in 35 cases (78%). Spontaneous bacterial clearance occurred in 138 (59%) untreated episodes (15 Type I, 23 Type II, 9 Type III and 91 Type IV). Negative control cultures tended to be more frequent in treated Type I (P = 0.09) and in untreated Type II episodes (P = 0.08). CONCLUSION: Restricting antibiotic treatments for asymptomatic low-grade bacteriuria and high-grade bacteriuria in the absence of pyuria, occurring later than 1 month posttransplantation, might be safe in RTR.

Duration of post-surgical antibiotic therapy for adult chronic osteomyelitis: a single-centre experience.

PURPOSE: The optimal duration of concomitant antibiotic therapy after surgical intervention for implant-free chronic osteomyelitis is unknown. No randomized data exist. Available recommendations are based on expert's opinion. We evaluated the duration of post-surgical antibiotic treatment related to remission of chronic osteomyelitis. METHODS: This was a retrospective single-centre study at Geneva University Hospitals with a minimal follow-up of two years after treatment. We used multivariate logistic regression analysis with exclusion of pediatric cases and of implant-related chronic osteomyelitis. RESULTS: A total of 49 episodes of implant-free chronic osteomyelitis in 49 adult patients were studied. The median number of surgical interventions was two (range, 1-10). The median duration of post-debridement antibiotic treatment was eight weeks (range, 4-14 weeks). Thirty-nine patients (80%) were in remission after a minimal follow-up of two years. In multivariate logistic regression analysis, one week of intravenous therapy had the same remission as two to three weeks (0.2, 0.1-1.9) or ≥ 3 weeks (0.3, 0.1-2.4). More than six weeks of total antibiotic treatment equalled ≤  six weeks (0.8, 0.1-5.2). CONCLUSIONS: In chronic osteomyelitis in adults, a post-debridement antibiotic therapy beyond six weeks, or an IV treatment longer than one week, did not show enhanced remission incidences. Prospective randomized trials are required to confirm this observation.

Six weeks of antibiotic treatment is sufficient following surgery for septic arthroplasty.

OBJECTIVES: In the treatment of prosthetic joint infections (PJI), the benefit of antibiotic therapy for more than 6 weeks after surgery is uncertain. We compared PJI cure rates according to the duration of antibiotics, 6 versus 12 weeks. METHODS: A prospective observational non-randomized study in Geneva University Hospitals 1996-2007. RESULTS: A total of 144 PJI (62 hip arthroplasties, 62 knee arthroplasties, and 20 hip hemiarthroplasties) were included with a prolonged follow-up ranging from 26 to 65 months. Surgical treatment included 60 débridements with implant retention, 10 one-stage exchanges of the prosthesis, 57 two-stage exchanges, and 17 Girdlestone procedures or knee arthrodeses. Seventy episodes (49%) received 6 weeks antibiotic therapy and 74 episodes, 12 weeks. Cure was achieved in 115 episodes (80%). Cure rate did not change according to the duration of intravenous antibiotics (>8 days, 8-21 days, >21 days) (Kruskal-Wallis-test; p = 0.37). In multivariate analysis, none of the following parameters was statistically significantly associated with cure: two-stage exchange (odds ratio 1.1,95%CI 0.2-4.8); number of débridements (0.9, 0.4-1.9); six weeks antibiotherapy (2.7, 0.96-8.3); duration of intravenous course (1.0, 0.96-1.03); sinus tract (0.6, 0.2-1.7); or MRSA infection (0.5, 0.2-1.5), although implant retention showed a tendency for less cure (0.3, 0.1-1.1). CONCLUSIONS: Following surgery for treatment of PJI, antibiotic therapy appears able to be limited to a 6-week course, with one week of intravenous administration. This approach needs confirmation in randomized trials.

Two consecutive deep sinus tract cultures predict the pathogen of osteomyelitis.

OBJECTIVES: The value of non-bone microbiological cultures in the diagnosis of osteomyelitis with sinus tract is not clear. We aimed to establish the concordance between deep sinus tract cultures and bone cultures in cases of osteomyelitis with a cutaneous fistula. METHODS: This was a non-randomized, prospective diagnostic trial at the Orthopedic Service of the University Hospital of Geneva. Each patient with osteomyelitis with a cutaneous sinus tract had four microbiological samples taken: two consecutive sinus tract cultures with bone contact at different times (samples A-1 and A-2), surgical bone biopsy performed through the sinus tract (sample B), and a surgical bone biopsy performed through an uninfected area outside the sinus tract (sample C), the latter considered as the 'gold standard'. RESULTS: One hundred and forty-one patients with 154 episodes of osteomyelitis were included in the study. When both sinus tract cultures yielded the same microorganism (86.4%), the concordance between both samples A and sample C was 96%. In the case of identical sinus tract culture infections, sensitivity was 91%, specificity 86%, and accuracy 90%. The accuracy in monomicrobial infections (50%) was higher than in polymicrobial infections (94.3% vs. 78.9%, respectively; p=0.02). CONCLUSIONS: In cases of monomicrobial osteomyelitis with sinus tract, two concordant tract cultures with bone contact accurately predict the pathogen.

An analysis of the factors influencing networkability in the health-care sector.

In most industries of economy, the production structures evolved into activities characterized by a high division of labour between the business partners combined with specialization, the standardization of service components and extensive networking. In the health-care sector, the first signs of a similar development are beginning to crystallize. As a consequence, networkability, the ability to link up with other players on the basis of commonly agreed standards for the joint provisioning of patient-centred and cost-efficient health services will emerge to a key concept for future health service delivery. As not only technical but mainly organizational and behavioural issues are actually determining networkability of health-care organizations, a holistic model for analysis is needed. In this paper, the main variables leading to an increase in this networkability are identified and compiled into a comprehensible procedure model for health-care practitioners.

Gram-negative bacteremia upon hospital admission: when should Pseudomonas aeruginosa be suspected?

BACKGROUND: Pseudomonas aeruginosa is an uncommon cause of community-acquired bacteremia among patients without severe immunodeficiency. Because tension exists between the need to limit unnecessary use of anti-pseudomonal agents and the need to avoid a delay in appropriate therapy, clinicians require better guidance regarding when to cover empirically for P. aeruginosa. We sought to determine the occurrence of and construct a model to predict P. aeruginosa bacteremia upon hospital admission. METHODS: A retrospective study was conducted in 4 tertiary care hospitals. Microbiology databases were searched to find all episodes of bacteremia caused by gram-negative rods (GNRs) 90 years, receipt of antimicrobial therapy within past 30 days, and presence of a central venous catheter or a urinary device. Among 250 patients without severe immunodeficiency, if no predictor variables existed, the likelihood of having P. aeruginosa bacteremia was 1:42. If >or= 2 predictors existed, the risk increased to nearly 1:3. CONCLUSIONS: P. aeruginosa bacteremia upon hospital admission in patients without severe immunodeficiency is rare. Among immunocompetent patients with suspected GNR bacteremia who have >or= 2 predictors, empirical anti-pseudomonal treatment is warranted.

Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial.

RATIONALE: The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. OBJECTIVES: To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock. METHODS: In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules. MEASUREMENTS AND MAIN RESULTS: Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03). CONCLUSIONS: Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.

Streptococcus sinensis endocarditis outside Hong Kong.

Streptococcus sinensis has been described as a causative organism for infective endocarditis in 3 Chinese patients from Hong Kong. We describe a closely related strain in an Italian patient with chronic rheumatic heart disease. The case illustrates that S. sinensis is a worldwide emerging pathogen.

Invasive zygomycosis in transplant recipients.

Zygomycosis are rare fungal infections occurring mainly in immunocompromised patients. To date only 160 cases have been published in transplant recipients. We report four new cases of zygomycosis in transplant recipients illustrating the large clinical spectrum of this infection: one disseminated infection with heart involvement and one rhinocerebral infection with dissemination in two bone marrow transplant recipients, one cutaneous infection in a liver and one pulmonary infection in a kidney recipient. All cases, except the cutaneous infection that was accessible to surgical resection and a systemic antifungal treatment, were fatal. In transplant recipients cumulating risk factors for zygomycosis, a high index of suspicion is required. Early diagnosis and combining surgery with systemic amphotericin-B are mandatory to improve survival rates.

Development and persistence of antimicrobial resistance in Pseudomonas aeruginosa: a longitudinal observation in mechanically ventilated patients.

Intubated patients frequently become colonized by Pseudomonas aeruginosa, which is subsequently responsible for ventilator-associated pneumonia. This pathogen readily acquires resistance against available antimicrobials. Depending on the resistance mechanism selected for, resistance might either be lost or persist after removal of the selective pressure. We investigated the rapidity of selection, as well as the persistence, of antimicrobial resistance and determined the underlying mechanisms. We selected 109 prospectively collected P. aeruginosa tracheal isolates from two patients based on their prolonged intubation and colonization periods, during which they had received carbapenem, fluoroquinolone (FQ), or combined beta-lactam-aminoglycoside therapies. We determined antimicrobial resistance phenotypes by susceptibility testing and used quantitative real-time PCR to measure the expression of resistance determinants. Within 10 days after the initiation of therapy, all treatment regimens selected resistant isolates. Resistance to beta-lactam and FQ was correlated with ampC and mexC gene expression levels, respectively, whereas imipenem resistance was attributable to decreased oprD expression. Combined beta-lactam-aminoglycoside resistance was associated with the appearance of small-colony variants. Imipenem and FQ resistance persisted for prolonged times once the selecting antimicrobial treatment had been discontinued. In contrast, resistance to beta-lactams disappeared rapidly after removal of the selective pressure, to reappear promptly upon renewed exposure. Our results suggest that resistant P. aeruginosa is selected in less than 10 days independently of the antimicrobial class. Different resistance mechanisms lead to the loss or persistence of resistance after the removal of the selecting agent. Even if resistant isolates are not evident upon culture, they may persist in the lung and can be rapidly reselected.