The effect of the acute phase of infection on absorption of and exposure to orally administered antibiotics in non-critically ill, hospitalized patients.

OBJECTIVES: During the acute phase of infection, IV antibiotics are preferred to ensure adequate systemic exposure. To assess whether adequate exposure may also be achieved with oral antibiotics, we investigated exposure to oral antibiotics and PTA during the acute phase of infection and after defervescence. METHODS: We enrolled hospitalized, non-critically ill febrile patients treated with IV antibiotics other than amoxicillin or ciprofloxacin. The study consisted of two visits: when patients had received <24 h IV treatment; and when patients had become afebrile. On both visits, patients received one additional dose of 750 mg amoxicillin, or 500 mg ciprofloxacin, depending on the presumed infection, after which serial blood samples were obtained. The primary endpoint was the ratio of the AUC during the febrile and the afebrile phase. The AUCs were considered to be equivalent when the ratio of the mean AUCs and its 90% CI was contained within the acceptance interval of 80%-125%. The secondary endpoint was PTA. RESULTS: Forty-four patients (15 amoxicillin, 29 ciprofloxacin) completed both study visits. The median time between the two study visits was 65.8 h (range 33.8-427.4). The ratio of the mean AUCs (study visit 1/study visit 2) was 97% (90% CI of 80%-117%) for amoxicillin and 112% (90% CI of 108%-116%) for ciprofloxacin. The PTA for amoxicillin and ciprofloxacin did not differ between the two phases and was adequate to treat common pathogens. CONCLUSIONS: The acute phase of infection in non-critically ill febrile patients does not influence the exposure to, or PTA of, orally administered amoxicillin and ciprofloxacin. This might justify earlier IV-to-oral switching.

Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry.

Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a reference strain were cultured while conidiation was prevented. Headspace samples were analyzed using a standardized method. Breath samples of patients from which the cultures were obtained were checked for the presence of the VOCs found in vitro. Each Aspergillus isolate produced a distinct VOC profile. These profiles could not be confirmed in exhaled breath in vivo.

Carriage of antibiotic-resistant Gram-negative bacteria after discontinuation of selective decontamination of the digestive tract (SDD) or selective oropharyngeal decontamination (SOD).

BACKGROUND: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) reduce colonization with antibiotic-resistant Gram-negative bacteria (ARGNB), incidence of nosocomial infections and improve survival in ICU patients. The effect on bacterial gut colonization might be caused by growth suppression by antibiotics during SDD/SOD. We investigated intestinal colonization with ARGNB after discharge from ICU and discontinuation of SDD or SOD. METHODS: We performed a prospective, observational follow-up study in regular hospital wards of three teaching hospitals in the Netherlands in patients discharged from the ICU, who were participating in a cluster randomized trial comparing SDD with SOD. We determined rectal carriage with ARGNB at ICU discharge (time (T) = 0) and 3, 6 and 10 days after discharge. The primary endpoint was time to first colonization with ARGNB that was not present at T = 0. Bacteria that are intrinsically resistant to antibiotics were not included in the primary analysis, but were included in post-hoc analysis. RESULTS: Of 1370 patients screened for inclusion, 996 patients had samples at T = 0 (507 after SDD and 489 after SOD). At ICU discharge, the prevalence of intestinal carriage with any ARGNB was 22/507 (4.3%) after SDD and 87/489 (17.8%) after SOD (p < 0.0001): 426 (SDD) and 409 (SOD) patients had at least one follow-up sample for analysis. The hazard rate for acquiring carriage of ARGNB after discontinuation of SDD, compared to SOD, in the ICU was 0.61 (95% CI 0.40-0.91, p = 0.02), and cumulative risks of acquisition of at least one ARGNB until day 10 were 13% (SDD) and 18% (SOD). At day 10 after ICU discharge, the prevalence of intestinal carriage with ARGNB was 11.3% (26/230 patients) after SDD and 12.5% (28/224 patients) after SOD (p = 0.7). In post-hoc analysis of all ARGNB, including intrinsically resistant bacteria, colonization at ICU discharge was lower after SDD (4.9 vs. 22.3%, p < 0.0001), but acquisition rates after ICU discharge were similar in both groups. CONCLUSIONS: Intestinal carriage at ICU discharge and the acquisition rate of ARGNB after ICU discharge are lower after SDD than after SOD. The prevalence of intestinal carriage with ARGNB at 10 days after ICU discharge was comparable in both groups, suggesting rapid clearance of ARGNB from the gut after ICU discharge. TRIAL REGISTRATION: Netherlands Trial Registry, NTR3311 . Registered on 28 february 2012.

Detection of Airway Colonization by Aspergillus fumigatus by Use of Electronic Nose Technology in Patients with Cystic Fibrosis.

Currently, there is no noninvasive test that can reliably diagnose early invasive pulmonary aspergillosis (IA). An electronic nose (eNose) can discriminate various lung diseases through an analysis of exhaled volatile organic compounds. We recently published a proof-of-principle study showing that patients with prolonged chemotherapy-induced neutropenia and IA have a distinct exhaled breath profile (or breathprint) that can be discriminated with an eNose. An eNose is cheap and noninvasive, and it yields results within minutes. We determined whether Aspergillus fumigatus colonization may also be detected with an eNose in cystic fibrosis (CF) patients. Exhaled breath samples of 27 CF patients were analyzed with a Cyranose 320. Culture of sputum samples defined the A. fumigatus colonization status. eNose data were classified using canonical discriminant analysis after principal component reduction. Our primary outcome was cross-validated accuracy, defined as the percentage of correctly classified subjects using the leave-one-out method. The P value was calculated by the generation of 100,000 random alternative classifications. Nine of the 27 subjects were colonized by A. fumigatus. In total, 3 subjects were misclassified, resulting in a cross-validated accuracy of the Cyranose detecting IA of 89% (P = 0.004; sensitivity, 78%; specificity, 94%). Receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.89. The results indicate that A. fumigatus colonization leads to a distinctive breathprint in CF patients. The present proof-of-concept data merit external validation and monitoring studies.

Changes in microbiota during experimental human Rhinovirus infection.

BACKGROUND: Human Rhinovirus (HRV) is responsible for the majority of common colds and is frequently accompanied by secondary bacterial infections through poorly understood mechanisms. We investigated the effects of experimental human HRV serotype 16 infection on the upper respiratory tract microbiota. METHODS: Six healthy volunteers were infected with HRV16. We performed 16S ribosomal RNA-targeted pyrosequencing on throat swabs taken prior, during and after infection. We compared overall community diversity, phylogenetic structure of the ecosystem and relative abundances of the different bacteria between time points. RESULTS: During acute infection strong trends towards increases in the relative abundances of Haemophilus parainfluenzae and Neisseria subflava were observed, as well as a weaker trend towards increases of Staphylococcus aureus. No major differences were observed between day-1 and day 60, whereas differences between subjects were very high. CONCLUSIONS: HRV16 infection is associated with the increase of three genera known to be associated with secondary infections following HRV infections. The observed changes of upper respiratory tract microbiota could help explain why HRV infection predisposes to bacterial otitis media, sinusitis and pneumonia.

Seroepidemiological studies indicate frequent and repeated exposure to Campylobacter spp. during childhood.

The annual number of episodes of clinical gastroenteritis caused by Campylobacter spp. in The Netherlands is estimated to be 75 000, i.e. once per 200 person life-years. This number is based on extrapolation of culture results from population-based studies. The number of culture-confirmed cases of Campylobacter infection peaks in the first 3 years of life and again between the ages of 20 and 25 years. The seroepidemiology of Campylobacter describes the relationship between age and exposure to Campylobacter and reflects both symptomatic and asymptomatic infections. Using a validated ELISA system, antibodies to Campylobacter were measured in an age-stratified sample (n=456) of the PIENTER serum collection of the Dutch general population. The seroprevalence of Campylobacter IgG antibodies increased with age, reaching almost 100% at age 20 years. Antibody levels steadily increased with age until young adulthood, suggesting repeated exposure to Campylobacter. In conclusion, seroepidemiological data demonstrated repeated exposures to Campylobacter throughout life, most of which do not lead to clinical symptoms. From young adulthood, >95% of the population in The Netherlands had serological evidence for exposure to Campylobacter.

A healthcare failure mode and effect analysis to optimise the process of blood culture performance.

BACKGROUND: Blood cultures are essential diagnostic tools to identify pathogens in systemic infections. However, logistics of blood culture performance is often suboptimal. This study analyses the pre-analytic phase of blood culture processing through different types of risk assessments. METHODS: We performed direct observations to gain in-depth knowledge of the root causes of suboptimal blood culture performance. These findings were summarised in a Bow-Tie chart. We then utilised a healthcare failure mode and effect analysis to prioritise failures per step in the process and to organise improvement activities. Finally, improvement actions were planned. RESULTS: Not obtaining a second set of blood cultures in the logistics of blood culture performance had the highest priority for action. Several failure modes, including human and system factors, were identified. Improvement actions included training and clinical lessons for nurses in the emergency department, updating hospital search engines to ease identification of relevant protocols, and an evaluation of the workload at the emergency department. Failure modes caused by human factors appear easy to address, however changing human behaviour is challenging. CONCLUSIONS: The analysis provided useful insight into the different steps in the logistics of blood culture performance and facilitated the organisation of actions focused on addressing the most urgent root causes.

[Treatment of recurrent Clostridium difficile-associated diarrhoea with a suspension of donor faeces]. / Behandeling van recidiverende Clostridium dificile-geassocieerde diarree met een suspensie van donorfeces.

OBJECTIVE: To study the effect of treating recurrent Clostridium difficile-associated diarrhoea (CDAD) with a suspension of donor faeces. DESIGN: Uncontrolled interventional study. METHOD: Patients that, despite adequate antibiotic therapy, had developed at least 2 recurrences ofCDAD, including at least one recurrence that had been treated with a vancomycin tapering regimen, were included in the study. Relatives or volunteers served as faeces donor. All donors were previously examined for the presence of HIV, hepatitis B- and C-virus, and acute infection with cytomegalovirus or Epstein-Barr virus. The donor faeces were examined for the presence of C. difficile, Yersinia, Campylobacter, Shigella, Salmonella, and parasites. Before the infusion of donor faeces, the patients were treated for 4 days with vancomycin 500 mg q.i.d., followed by colon lavage. The suspension of 150 g of donor faeces dissolved in 300-400 ml of NaCl was infused into the jejunum via a duodenal catheter or into the caecum via colonoscopy. RESULTS: 7 CDAD patients were included and treated, including 2 with the hypervirulent C. difficile-strain PCR ribotype 027, toxinotype III. In 5 patients, the defaecation frequency returned to normal almost immediately after treatment and the cultures and toxin tests for C. difficile were repeatedly negative. In the remaining 2 patients, the treatment was successful after a repeated infusion of faeces from a different donor. CONCLUSION: Treatment with donor faeces seems promising for patients who develop repeated recurrences despite adequate therapy and could be valuable in the future during (local) epidemics of the PCR ribotype 027 strain. A randomised nationwide study (FECAL trial) has been started in order to determine the efficacy of this treatment.

Validation of an ELISA for the diagnosis of recent Campylobacter infections in Guillain-Barré and reactive arthritis patients.

Weeks or months following Campylobacter infection, a small proportion of infected individuals develop Guillain-Barré syndrome (GBS) or reactive arthritis (ReA). Stool culture for Campylobacter is often negative in these patients, and serology is therefore the method of choice for diagnosing a recent infection with Campylobacter. This study developed a capture ELISA system to detect anti-Campylobacter IgA and IgM antibodies indicative of a recent infection. The sensitivity of the assay was 82.0% in uncomplicated Campylobacter enteritis patients, 96.2% in GBS patients who were culture-positive for Campylobacter, and 93.1% in culture-positive ReA patients, with a specificity of 93.0%. The assay allows identification of Campylobacter infection in patients with post-infectious neurological and rheumatological complications.

Characteristics and incidence of Clostridium difficile-associated disease in The Netherlands, 2005.

During a 2-month period in 2005, 13 laboratories participated in a surveillance study of Clostridium difficile-associated disease (CDAD) in 17 hospitals in The Netherlands. The median incidence rate of CDAD was 16/10 000 patient admissions (2.2/10 000 patient-days) and varied from 1 to 46/10 000 patient admissions according to hospital. In total, 81 patients with CDAD were reported; 49 (61%) patients had nosocomial CDAD, and 29 (36%) patients were admitted to hospital when already suffering from diarrhoea. Two (2%) deaths were attributable to CDAD; both of these patients were admitted with severe community-onset CDAD and were aged >80 years. Among 64 toxinogenic isolates, ten (16%) belonged to PCR ribotype 027 and ten (16%) to PCR ribotype 014. Type 027 was identified in ten patients from one hospital during an unrecognised outbreak. Toxinotyping of the 64 isolates revealed the presence of six different toxinogenic types, with 41 (64%) isolates of toxinotype 0, ten (16%) isolates of toxinotype III, and nine (14%) isolates of toxinotype V. Of the 64 toxinogenic isolates, seven (11%) had a 39-bp deletion in the tcdC gene, 11 (17%) had an 18-bp deletion, and one (1%) had a deletion of c. 44 bp. Genes for binary toxin were present in 21 (33%) of the 64 toxinogenic isolates, mainly associated with toxinotypes III and V. It was concluded that the median CDAD incidence rate of 16/10 000 patient admissions in The Netherlands is considerably lower than that in Canada and the USA, and that the emerging type 027 can spread unnoticed. The high proportion (36%) of CDAD cases with a community onset has important implications for future studies of the epidemiology of CDAD.

Effect of an antibiotic checklist on length of hospital stay and appropriate antibiotic use in adult patients treated with intravenous antibiotics: a stepped wedge cluster randomized trial.

OBJECTIVES: Quality indicators (QIs) have been developed to define appropriate antibiotic use in hospitalized patients. We evaluated whether a checklist based on these QIs affects appropriate antibiotic use and length of hospital stay. METHODS: An antibiotic checklist for patients treated with intravenous antibiotics was introduced in nine Dutch hospitals in a stepped wedge cluster randomized trial. Prophylaxis was excluded. We included a random sample before (baseline), and all eligible patients after (intervention) checklist introduction. Baseline and intervention outcomes were compared. Primary endpoint was length of stay (LOS), analysed by intention to treat. Secondary endpoints, including QI performances, QI sum score (performance on all QIs per patient), and quality of checklist use, were analysed per protocol. RESULTS: Between 1 November 2014 and 1 October 2015 we included 853 baseline and 5354 intervention patients, of whom 993 (19%) had a completed checklist. The LOS did not change (baseline geometric mean 10.0 days (95% CI 8.6-11.5) versus intervention 10.1 days (95% CI 8.9-11.5), p 0.8). QI performances increased between +3.0% and +23.9% per QI, and the percentage of patients with a QI sum score above 50% increased significantly (OR 2.4 (95% CI 2.0-3.0), p<0.001). Higher QI sum scores were significantly associated with shorter LOS. Discordance existed between checklist-answers and actual performance. CONCLUSIONS: Use of an antibiotic checklist resulted in a significant increase in appropriateness of antibiotic use, but not in a reduction of LOS. Low overall checklist completion rates and discordance between checklist-answers and actual provided care might have attenuated the impact of the checklist.

eNose technology can detect and classify human pathogenic molds in vitro: a proof-of-concept study of Aspergillus fumigatus and Rhizopus oryzae.

Invasive pulmonary mold disease (IPMD) is often fatal in neutropenic patients. This is because IPMD is difficult to diagnose timely, especially when non-Aspergillus molds are the causative agent, as they are usually not associated with a positive galactomannan assay. In 2013 we showed that exhaled breath analysis might be used to diagnose invasive aspergillosis through profiling of patterns in exhaled volatile organic compounds (VOCs) by electronic nose (eNose) technology. The current study aimed to determine (1) whether molds can be discriminated from other microorganisms (using two mold species: Aspergillus fumigatus and a pathogenic mold not associated with a positive galactomannan assay, i.c. Rhizopus oryzae) and (2) whether both molds can be discriminated from each other. First, we cultured strains of Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, A. fumigatus and R. oryzae in separate airtight bottles. We examined whether an eNose (Cyranose 320) could discriminate the headspaces of bottles with molds from those with bacteria/yeasts. Second, we examined whether an eNose could discriminate A. fumigatus and R. oryzae. Diagnostic algorithms were created using canonical discriminant analysis after principle component analysis. Primary outcome parameter was the validated accuracy. The eNose discriminated A. fumigatus from bacteria/yeasts with a cross-validated accuracy of 92.9% (sensitivity 95.2%, specificity 91.9%). The eNose had an accuracy (validated using split-half analysis) of 100% in discriminating A. fumigatus from R. oryzae. Our study suggests that an eNose can identify and classify molds in vitro. This warrants prospective in vivo studies aimed at detecting and classifying IPMD using exhaled breath.

[Life-threatening infections with a new strain of Clostridium difficile]. / Levensbedreigende infecties met een nieuwe variant van Clostridium difficile.

Three men, aged 39, 73, and 66 years, respectively, developed an infection with a new strain ofClostridium difficile, ribotype 027.C.difficile-associated diarrhoea (CDAD) occurred in two patients after multiple abdominal surgery and in the third patient one week after autologous haematopoietic cell transplantation. Within a few days, despite antibiotic therapy, all three patients developed severe (pseudomembranous) colitis with sepsis for which admission to the Intensive Care Unit was required. Two patients underwent (sub)total colectomy and received an intensive course of oral and/or rectal vancomycin. In all patients who develop diarrhoea in hospital, especially during or after treatment with antibiotics or chemotherapeutic agents, an infection with C. difficile ribotype 027 should be suspected. Recent outbreaks of this hypervirulent strain of C. difficile have been reported in Canada, the United States, United Kingdom, and The Netherlands. Demonstration of C. difficile toxin in faeces confirms the clinical suspicion of CDAD and ribotyping of the strain may reveal whether the 027 strain is present. For treatment of these 027 infections, vancomycin is preferred to metronidazole. After a severe course of colitis or in case of recurrence a 'tapering and pulse' course ofvancomycin can be prescribed; alternatively, treatment with bovine antibody-enriched whey may be considered. The introduction of this hypervirulent strain has led to reinforcement of the hygienic measures in accordance with the recommendations of the Dutch Working Party on Infection Prevention and a policy to deter the use of fluoroquinolones.

First experiences with an accelerated CMV antigenemia test: CMV Brite Turbo assay.

BACKGROUND: Cytomegalovirus disease is still a major problem in immunocompromised patients, such as bone marrow or kidney transplantation patients. The detection of viral antigen in leukocytes (antigenemia) has proven to be a clinically relevant marker of CMV activity and has found widespread application. Because most existing assays are rather time-consuming and laborious, an accelerated version (Brite Turbo) of an existing method (Brite) has been developed. The major modification is in the direct lysis of erythrocytes instead of separation by sedimentation. OBJECTIVE: In this study the Brite Turbo method has been compared with the conventional Brite method to detect CMV antigen pp65 in peripheral blood leukocytes of 107 consecutive immunocompromised patients. RESULTS: Both tests produced similar results. Discrepancies were limited to the lowest positive range and sensitivity and specificity were comparable for both tests. CONCLUSIONS: Two major advantages of the Brite Turbo method could be observed in comparison to the original method: assay-time was reduced by more than 50% and only 2 ml of blood was required. An additional advantage was the higher number of positive nuclei in the Brite Turbo method attributable to the increased number of granulocytes in the assay. Early detection of CMV infection or reactivation has become faster and easier with this modified assay.

Microwave irradiation and cross-linking of collagen.

In a multifactorial experiment, dermal sheep collagen was treated in diluted glutaraldehyde solutions, 70% ethyl alcohol, Cialit 1:5000, and distilled water for 1, 3 and 5 min, respectively, in combination with microwave irradiation at different temperature settings. The shrinkage temperature indicating the degree of cross-linking achieved was then determined. Treatment in 0.65% glutaraldehyde with microwave irradiation setting for 60 degrees C resulted in the maximum shrinkage temperature within 1 min, whilst at the lower setting of 50 degrees C, the maximum shrinkage temperature for both glutaraldehyde solutions is only reached after 5 min. Neither microwave irradiation by itself, Cialit or ethyl alcohol induce cross-linking of collagen fibres. These findings are relevant for implant studies.

Microwave treatment of xenogeneic cartilage transplants.

Human rib cartilage was irradiated with microwaves according to six different methods and transplanted into rabbits. Untreated rib cartilage preserved in Cialit served as a control. After 12 and 40 wk of implantation, the microscopic appearance of these xenogeneic cartilage transplants was given a score in comparison with the transplants preserved in Cialit. The microwave treatment of the cartilage appeared to improve the results. The Cialit-preserved transplants showed progressive resorption by macrophages with central necrosis and fragmentation, which was not present in the microwave-treated grafts. Microwaves seem to stabilize the cartilage matrix and enhance the diffusion of fixatives. Irradiation in ethanol as an immersion fluid appeared to be the best method. The results of transplantation can benefit from the use of microwaves in the preservation of the cartilage. It is argued that, in addition, microwave irradiation might be used for inactivation of human immunodeficiency virus in human cartilage used for transplantation.

Amyotrophic lateral sclerosis: mortality risk during the course of the disease and prognostic factors. The Netherlands ALS Consortium.

We performed a historical cohort study of 307 untreated patients with probable or definite amyotrophic lateral sclerosis in order to investigate whether the mortality risk changed during the disease course and to identify prognostic factors at diagnosis. Patients were diagnosed in one of the academic hospitals in The Netherlands and followed-up for at least 6 years after diagnosis. The median survival from diagnosis was 1.4 years (95% confidence interval, 1.3-1.6 years) with an estimated 5- and 10-year survival of 20 and 8%, respectively. Mortality was at its maximum in the second year after diagnosis and declined considerably thereafter. Observed mortality approached the expected mortality in patients who survived diagnosis 6 or more years. In univariate and multivariate analyses, young age, limb onset, and a long delay between initial weakness and diagnosis were associated with lower mortality. The better prognosis of limb-onset patients was not observed in females. Patients with initial respiratory muscle weakness, had the worst prognosis with a median survival of only 2 months. The significantly greater mortality of older patients proved not to result from a rise in expected mortality only. In conclusion, the annual mortality risk in ALS does not remain constant throughout the disease and depends on age at diagnosis, site of onset, diagnostic delay, but also on the time since diagnosis. These findings may have consequences for the planning of symptomatic care and the design and analysis of therapeutic trials.

Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a CAPD peritonitis.

OBJECTIVE: To investigate whether or not a change in dialysate interleukin-8 (IL-8) concentration precedes the onset of clinically overt peritonitis and is significant in the recruitment of granulocytes during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients stored their overnight effluent at 4 degrees C, which was routinely thrown away after 2 days. If peritonitis developed, patients delivered their effluent of the preceding two nights and the peritonitis effluent for analysis. A control study was performed 1 to 3 months after recovery. Dialysate samples were analyzed for number of cells, differential cell count, IL-8 and elastase concentrations, and their neutrophil chemoattractive capacity. In addition, serum samples during peritonitis were analyzed for IL-8 concentrations. RESULTS: Ten peritonitis episodes in 7 patients were analyzed. Numbers of neutrophils and levels of dialysate IL-8 and elastase started to increase 4 to 12 hours before the first peritonitis effluent. The dialysate/serum IL-8 ratio was 423.5 during peritonitis and 7.0 in the postperitonitis controls. There was a significant correlation between the number of neutrophils and IL-8 concentration in the dialysate. The in vitro neutrophil chemotaxis was increased toward the peritonitis effluents, as compared to control effluents. Incubation of the peritonitis effluents with anti-IL-8 monoclonal antibody blocked the increase in neutrophil chemotaxis above control levels by an average of 26.7%. CONCLUSION: IL-8 is produced in the peritoneal cavity during CAPD treatment and may mediate part of the neutrophil recruitment and degranulation in the initial phase of a CAPD peritonitis.

Immunobiology of Langerhans' cells migrating into aural cholesteatomas.

Immunohistochemical and submicroscopic analyses of human cholesteatoma matrices reveal the presence of Langerhans' cells and T lymphocytes. Through cell-to-cell interaction, Langerhans' cells probably play a key role in skin-related disorders, including cholesteatomas. They originate from a mobile cell population of monocyte origin and migrate into and out of the body's lining. Their custodial function is always carried out in close relation with T lymphocytes. Various monoclonal antibodies directed against Langerhans' cell and T lymphocyte membrane receptors reveal the presence of these cell populations in cholesteatoma matrices but not in the tympanic membrane. Langerhans' cell and T cell traffic through cholesteatomas are discussed in relation to the pathogenesis, natural course, and recurrence rate of cholesteatomas. Through immunopathologic evaluation the clinical aggressiveness of a cholesteatoma will probably become predictable. Medical manipulation of Langerhans' cell and T cell functions- as an adjuvant to surgery - may have consequences for the future handling of cholesteatomas.