Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.

Pneumococcal pericarditis in a patient with newly diagnosed diabetes mellitus: a case report.

BACKGROUND: After the introduction of antibiotics, pneumococcal pericarditis has become a rare finding. However, this severe condition with high mortality and complication rates requires rapid recognition and intervention. Herein, we describe a patient that presents with this rare disease resulting in an unusual, fatal outcome. CASE PRESENTATION: A previously healthy, 68-year-old, Caucasian male presented with progressive fatigue, dyspnea, and appetite loss since 12 days. He was diagnosed with diabetes mellitus 5 days before presentation but had not started treatment. After echocardiography revealed pericardial effusion, pericardiocentesis was performed with immediate drainage of a large volume of purulent fluid suggestive of bacterial pericarditis. On the basis of cultures showing Streptococcus pneumoniae as the causative organism, a regimen of intravenous penicillin was initiated. Additionally, antidiabetic drugs were started as his diabetes also predisposed him to invasive infectious disease. No other primary source of the infection, such as pneumonia, was found. Though the patient was found to be severely ill on admission, his clinical condition improved. A total of 1235 mL of pericardial fluid was drained, and adequate drainage was confirmed by daily, bedside echocardiography. However, 6 days post-admission, the patient suddenly developed intrapericardial bleeding with blood clot formation on the right chamber with subsequent cardiac tamponade. With the blood clot precluding adequate drainage through the catheter, the patient suffered cardiac arrest and died before surgical intervention could be attempted. CONCLUSIONS: Pneumococcal pericarditis is a very rare but life-threatening disease that necessitates immediate intervention with antibiotics and drainage of the pericardial effusion. Thus, although symptoms may be variable and aspecific, early recognition of this condition is critical. The present case illustrates the presentation, diagnosis, and clinical course of a patient presenting with pneumococcal pericarditis in current clinical practice. Through this report, we aimed to increase awareness among clinicians both of the existence of this phenomenon and of its uncertain clinical course. As is highlighted by the case, patients with pneumococcal pericarditis are at high risk for complications and should be closely monitored.

Narrow-spectrum antibiotics for community-acquired pneumonia in Dutch adults (CAP-PACT): a cross-sectional, stepped-wedge, cluster-randomised, non-inferiority, antimicrobial stewardship intervention trial.

BACKGROUND: Adults hospitalised to a non-intensive care unit (ICU) ward with moderately severe community-acquired pneumonia are frequently treated with broad-spectrum antibiotics, despite Dutch guidelines recommending narrow-spectrum antibiotics. Therefore, we investigated whether an antibiotic stewardship intervention would reduce the use of broad-spectrum antibiotics in patients with moderately severe community-acquired pneumonia without compromising their safety. METHODS: In this cross-sectional, stepped-wedge, cluster-randomised, non-inferiority trial (CAP-PACT) done in 12 hospitals in the Netherlands, we enrolled immunocompetent adults (≥18 years) who were admitted to a non-ICU ward and had a working diagnosis of moderately severe community-acquired pneumonia. All participating hospitals started in a control period and every 3 months a block of two hospitals transitioned from the control to the intervention period, with all hospitals eventually ending in the intervention period. The unit of randomisation was the hospital (cluster), and electronic randomisation (by an independent data manager) decided the sequence (the time of intervention) by which hospitals would cross over from the control period to the intervention period. Blinding was not possible. The antimicrobial stewardship intervention was a bundle targeting health-care providers and comprised education, engaging opinion leaders, and prospective audit and feedback of antibiotic use. The co-primary outcomes were broad-spectrum days of therapy per patient, tested by superiority, and 90-day all-cause mortality, tested by non-inferiority with a non-inferiority margin of 3%, and were analysed in the intention-to-treat population, comprising all patients who were enrolled in the control and intervention periods. This trial was prospectively registered at ClinicalTrials.gov, NCT02604628. FINDINGS: Between Nov 1, 2015, and Nov 1, 2017, 5683 patients were assessed for eligibility, of whom 4084 (2235 in the control period and 1849 in the intervention period) were included in the intention-to-treat analysis. The adjusted mean broad-spectrum days of therapy per patient were reduced from 6·5 days in the control period to 4·8 days in the intervention period, yielding an absolute reduction of -1·7 days (95% CI -2·4 to -1·1) and a relative reduction of 26·6% (95% CI 18·0-35·3). Crude 90-day mortality was 10·9% (242 of 2228 died) in the control period and 10·8% (199 of 1841) in the intervention period, yielding an adjusted absolute risk difference of 0·4% (90% CI -2·7 to 2·4), indicating non-inferiority. INTERPRETATION: In patients hospitalised with moderately severe community-acquired pneumonia, a multifaceted antibiotic stewardship intervention might safely reduce broad-spectrum antibiotic use. FUNDING: None.

The diagnostic value of nasal microbiota and clinical parameters in a multi-parametric prediction model to differentiate bacterial versus viral infections in lower respiratory tract infections.

BACKGROUND: The ability to accurately distinguish bacterial from viral infection would help clinicians better target antimicrobial therapy during suspected lower respiratory tract infections (LRTI). Although technological developments make it feasible to rapidly generate patient-specific microbiota profiles, evidence is required to show the clinical value of using microbiota data for infection diagnosis. In this study, we investigated whether adding nasal cavity microbiota profiles to readily available clinical information could improve machine learning classifiers to distinguish bacterial from viral infection in patients with LRTI. RESULTS: Various multi-parametric Random Forests classifiers were evaluated on the clinical and microbiota data of 293 LRTI patients for their prediction accuracies to differentiate bacterial from viral infection. The most predictive variable was C-reactive protein (CRP). We observed a marginal prediction improvement when 7 most prevalent nasal microbiota genera were added to the CRP model. In contrast, adding three clinical variables, absolute neutrophil count, consolidation on X-ray, and age group to the CRP model significantly improved the prediction. The best model correctly predicted 85% of the 'bacterial' patients and 82% of the 'viral' patients using 13 clinical and 3 nasal cavity microbiota genera (Staphylococcus, Moraxella, and Streptococcus). CONCLUSIONS: We developed high-accuracy multi-parametric machine learning classifiers to differentiate bacterial from viral infections in LRTI patients of various ages. We demonstrated the predictive value of four easy-to-collect clinical variables which facilitate personalized and accurate clinical decision-making. We observed that nasal cavity microbiota correlate with the clinical variables and thus may not add significant value to diagnostic algorithms that aim to differentiate bacterial from viral infections.

18F-fluoro-2-deoxyglucose positron emission tomography-negative endocarditis lenta caused by Bartonella henselae.

It has been suggested that 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) might serve as a tool for the often difficult diagnosis of infective endocarditis. The case is described of a patient with a Bartonella henselae endocarditis with a negative FDG-PET. This case report demonstrates that negative FDG-PET findings do not rule out the presence of endocarditis.

[Scombroid food poisoning among hospital personnel]. / Scombroïde-intoxicatie onder ziekenhuispersoneel.

BACKGROUND: Scombroid food poisoning is caused by eating fish with a high concentration of histamine. Histamine is converted from histidine in fish of the Scombroidea family if it is not stored at a sufficiently low temperature. The clinical picture resembles an allergic reaction. CASE DESCRIPTION: Twenty-one of our hospital personnel went to the ER, mostly reporting flushing, headache, palpitations and gastro-intestinal symptoms. They had all eaten tuna salad in the staff canteen. The symptoms appeared to be caused by scombroid food poisoning. CONCLUSION: As a result of early recognition of the clinical picture and prompt crisis management we were able to prevent the outbreak spreading further.

Antiviral activity of HIV type 1 protease inhibitors nelfinavir and indinavir in vivo is not influenced by P-glycoprotein activity on CD4+ T cells.

P-glycoprotein (P-gp) can compromise the antiretroviral effect of a protease inhibitor (PI)-containing regimen for HIV-1, but can also reduce HIV-1 replication. We studied the net effect of P-gp on the intracellular HIV-1 RNA and DNA load in vivo. CD4(+) T cells were isolated from 27 HIV-1 patients (13 without and 14 with a PI-containing regimen) and subsequently sorted in CD45RO(-) (naive) and CD45RO(+) (memory) subsets with either high (P-gp(high)) or low (P-gp(low)) P-gp activity. Unspliced HIV-1 RNA and HIV-1 DNA load were determined. For each patient P-gp(high) and P-gp(low) subsets were compared. In patients on a PI-containing regimen, intracellular unspliced HIV-1 RNA was significantly lower in P-gp(high)-naive CD4(+) cells compared to P-gp(low)-naive CD4(+) cells (p = 0.04). The same trend was seen in naive CD4(+) cells of treatment naive patients. In both treated and untreated patients HIV-1 DNA levels were significantly lower in P-gp(high) than in P-gp(low) memory CD4(+) cells (p = 0.02 and p = 0.04). High cellular P-gp activity coincided with a reduced intracellular HIV-1 load in vivo, both in therapy-naive and in PI-treated patients. Therefore we conclude that the potential efflux function of P-gp on PIs may be clinically less relevant than the effect of P-gp on intracellular HIV-1 replication.

Analysis of the effect of highly active antiretroviral therapy during acute HIV-1 infection on HIV-specific CD4 T cell functions.

BACKGROUND: It has been reported that antiretroviral therapy (HAART) during acute HIV-1 infection may rescue HIV-1-specific CD4 T cell responses. OBJECTIVE: To determine the duration of this preserved response by investigating the long-term effects of HAART during acute infection on HIV-specific CD4 T cell function related to possible immune control during subsequent therapy interruption. METHODS: A longitudinal analysis followed HIV-specific CD4 T cell reactivity in 17 individuals with well-documented acute HIV-1 infection where five out of 11 HAART-treated patients stopped therapy and six were untreated. Peripheral blood mononuclear cells were stimulated with overlapping peptide pools derived from Gag and Nef. Production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by CD4 T cells was analysed together with proliferative responses. RESULTS: Absolute numbers, but not percentages, of Gag-specific IFN-gamma-, IL-2- or IFN-gamma/IL-2-producing CD4 T cells were increased in treated compared with untreated individuals up to 2 years after seroconversion. HAART during acute HIV-1 infection was associated with lower viral load but did not result in increased proliferation of HIV-specific CD4 T cells. One out of five individuals who discontinued therapy showed evidence for immune control. However, patients who failed to control viraemia also had measurable proliferative HIV-specific CD4 T cell responses and preserved numbers of cytokine-producing CD4 T cells. CONCLUSIONS: Early HAART during acute HIV-1 infection resulted in higher numbers of HIV-specific IFN-gamma- and IL-2-producing CD4 T cells, but this preservation in four out of five patients was not associated with control of viraemia upon treatment interruption.

Short communication: No detrimental immunological effects of mycophenolate mofetil and HAART in treatment-naive acute and chronic HIV-1-infected patients.

Mycophenolate mofetil has been proposed for HIV-1 therapy because of its guanine-depleting effect, which is expected to interfere with HIV-1 replication directly by hampering reverse transcription and indirectly via inhibition of CD4+ T cell proliferation. However, treatment with mycophenolate mofetil might also compromise lymphocyte reconstitution and HIV-specific immunity. Therefore we longitudinally studied the effects of mycophenolate mofetil in combination with HAART on T cell proliferation, lymphocyte reconstitution, and HIV-specific CD4+ and CD8+ T cell responses in six therapy-naive, acute or chronic HIV-1-infected patients, as compared to eight patients treated with HAART alone. T cell proliferation in whole blood cultures of patients treated with mycophenolate mofetil was inhibited. Strikingly, ex vivo Ki67 expression within T cells was not influenced by treatment with mycophenolate mofetil. In vitro studies showed that Ki67 expression occurs at an early step of the cell cycle and was not inhibited by guanine depletion. When treatment with mycophenolate mofetil was stopped a transient increase in apoptosis and Ki67-expressing T cells was detected. This observation together with near complete inhibition of T cell proliferation in whole blood cultures during treatment with mycophenolate mofetil indicated that T cell proliferation was inhibited in patients treated with mycophenolate mofetil. Still, there was no evidence for detrimental effects of treatment with mycophenolate mofetil in addition to HAART on CD4+ T cell reconstitution or HIV-specific immunity.

Clinical relevance of Corynebacterium pseudodiphtheriticum in lower respiratory tract specimens.

BACKGROUND: Corynebacterium pseudodiphtheriticum may be present as commensal flora of the respiratory tract and therefore it may be difficult to assess clinical relevance when it is cultured from lower respiratory tract specimens. Our objective was to determine the clinical relevance of C. pseudodiphtheriticum as a lower respiratory tract pathogen and to define patients at risk of developing lower respiratory tract infections caused by C. pseudodiphtheriticum. METHODS: We retrospectively identified all lower respiratory tract cultures positive for C. pseudodiphtheriticum over a 10-year period and assessed clinical relevance by predefined criteria. RESULTS: Clinical relevance was likely or possible in 86% of patients. Pre-existent comorbidity was present in 86% of patients, mostly underlying cardiac or pulmonary disease. All isolates were susceptible to amoxicillin. CONCLUSION: C. pseudodiphtheriticum should be considered a clinically relevant pathogen when cultured from the lower respiratory tract in symptomatic patients.

Highly active antiretroviral therapy with or without mycophenolate mofetil in treatment-naive HIV-1 patients.

OBJECTIVE: To study the effect of mycophenolate mofetil (MMF) on the decay rate of plasma HIV-1 RNA and the latently infected cellular reservoir in treatment-naive patients starting antiretroviral therapy. DESIGN: : Randomized trial. METHODS: A group of 19 HIV-1 infected patients (9 with a chronic and 10 with a primary infection) starting a triple antiretroviral drug regimen were randomized to a group with or without MMF. Plasma samples for HIV-1 RNA were taken and HLA-DR-CD4+ T cells were co-cultured for HIV-1 isolation. Slopes of plasma HIV-1 RNA and cellular viral load decay were calculated for the first 14 days and the first 24 weeks of treatment, respectively. RESULTS: The median plasma HIV-1 RNA daily decay rate in chronically infected patients was 0.25 log10 copies/ml [interquartile range (IQR), 0.18-0.30] with MMF and 0.28 log10 copies/ml (IQR, 0.22-0.32) without MMF (P = 0.56); in primary infected patients, it was 0.31 log10 copies/ml (IQR, 0.31-0.32) with MMF and 0.32 log10 copies/ml (IQR, 0.26-0.34) without MMF (P = 0.75). The median daily decay rate of latently infected cells was 0.017 and 0.004 infected cells/10 cells in patients with and without MMF, respectively (P = 0.89). The increase in CD4 T cells was comparable between patients with and without MMF. After stopping MMF, there was an increase in the cellular reservoir in six of eight patients. CONCLUSION: The addition of MMF to a triple class antiretroviral regimen in treatment-naive patients does not significantly increase the plasma HIV-1 RNA decay rate or the decay rate of the latently infected cellular reservoir.

TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen.

OBJECTIVE: TMC125, a next generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), demonstrated a remarkable decline of plasma HIV-1 RNA during a phase IIa study. We compared the initial rate of decline of plasma HIV-1 RNA achieved by TMC125 monotherapy with that of a triple class, five-drug regimen, containing drugs from all three currently licensed classes (zidovudine, lamivudine, abacavir, indinavir and nevirapine). METHODS: The decline in plasma HIV-1 RNA of 12 HIV-1 infected, antiretroviral (ART) naive patients treated for 1 week with TMC125 monotherapy was compared with that observed in the ERA study (n = 11). The plasma HIV-1 RNA elimination rate constant was calculated based on at least four plasma HIV-1 RNA measurements during the first week of treatment (first-order elimination) and compared using the Student's t test. RESULTS: Median ages were 23 and 38 years for TMC125 and ERA patients, respectively (P = 0.001), median baseline plasma HIV-1 RNA levels were 4.2 and 4.8 log10 copies/ml (P = 0.001) and median baseline CD4 T-cell counts were 458 x 10(6) and 360 x 10(6) cells/l (P = 0.08). The median plasma HIV-1 RNA elimination rate constant was 0.68/day in TMC125 treated patients, and 0.56/day in ERA participants (P = 0.24). The median decline in plasma HIV-1 RNA after 7 days was 1.92 and 1.76 log10 copies (P = 0.77) and the median increase of CD4 T cells was 119 x 10(6) and 60 x 10(6) cells/l, respectively (P = 0.29). CONCLUSION: Monotherapy with TMC125 in ART-naive, HIV-1-infected individuals resulted in a similar rate of decline of plasma HIV-1 RNA during 1 week of therapy as therapy with a five-drug regimen.

Dynamics of the pool of infected resting CD4 HLA-DR- T lymphocytes in patients who started a triple class five-drug antiretroviral regimen during primary HIV-1 infection.

Starting standard antiretroviral therapy within 10 days after the onset of a primary HIV-1 infection cannot prevent the establishment of a reservoir of HIV-1-infected memory CD4 T cells. Here we studied the reservoir of HIV-1-infected memory CD4 T cells in four patients who started a triple class, five-drug regimen during primary HIV-1 infection. There was a strong correlation between the proportion of productively infected CD4 HLA-DR- T lymphocytes and plasma HIV-1 RNA levels (r=0.852; P<0.001) during the first 24 weeks of therapy. Within 45 weeks of treatment, in three of the four patients the proportion of productively infected CD4 HLA-DR- T lymphocytes was reduced below the level of quantification. In the fourth patient the cellular reservoir remained quantifiable. In two patients who stopped therapy 44 weeks after initiation an immediate rebound of the plasma HIV-1 RNA level and the proportion of productively infected CD4 HLA-DR- T lymphocytes occurred. In conclusion, initiation of a potent five-drug, triple class regimen during primary HIV-1 infection does not result in virus-specific immune control upon discontinuation of therapy after 44 weeks. Therefore, longer or even stronger suppression of viral replication might be necessary to achieve this goal in primary HIV-1 infection.

Effect of mycophenolate mofetil on the pharmacokinetics of antiretroviral drugs and on intracellular nucleoside triphosphate pools.

OBJECTIVE: To study the effect of mycophenolate mofetil therapy on the pharmacokinetic parameters of a number of antiretroviral drugs, on intracellular pools of deoxycytidine triphosphate (dCTP) and deoxyguanosine triphosphate (dGTP), and on intracellular concentrations of the triphosphate of lamivudine (3TCTP). DESIGN: Randomised pharmacokinetic study. PARTICIPANTS: Nineteen HIV-1-infected patients. METHODS: Antiretroviral-naive men starting treatment with didanosine 400 mg once daily, lamivudine 150 mg twice daily, abacavir 300 mg twice daily, indinavir 800 mg twice daily, ritonavir 100 mg twice daily and nevirapine 200 mg twice daily were randomised to a group with or without mycophenolate mofetil 500 mg twice daily. After 8 weeks of therapy, the plasma pharmacokinetic profiles of mycophenolic acid (the active metabolite of mycophenolate mofetil), abacavir, indinavir and nevirapine, and triphosphate concentrations (dCTP, dGTP and 3TCTP) in peripheral blood mononuclear cells, were determined. RESULTS: Nine of the 19 patients received mycophenolate mofetil. There was no difference in plasma clearance of indinavir or abacavir between the two groups. The clearance of nevirapine was higher in patients using mycophenolate mofetil (p = 0.04). In 12 patients, of whom five also received mycophenolate mofetil, intracellular triphosphates were measured. There was no significant difference in intracellular dCTP, dGTP or 3TCTP concentrations between the two groups. CONCLUSION: In this small cohort of patients, mycophenolate mofetil therapy reduced the plasma concentration of nevirapine but had no effect on plasma concentrations of indinavir and abacavir. There were no consistent effects of mycophenolic acid on the intracellular concentrations of dCTP, dGTP or 3TCTP.

[Mycoplasma-pneumoniae-associated mucositis]. / Mucositis bij longontsteking door Mycoplasma.

BACKGROUND: The pathogen Mycoplasma pneumonia is a frequent cause of respiratory tract infections, especially in adolescents. Less well known is that this infection may also be associated with extrapulmonary manifestations including M. pneumonia associated mucositis (MPAM). CASE DESCRIPTION: A 19-year-old Dutch man was admitted to the hospital with severe mucositis, stomatitis, bilateral conjunctivitis, urethritis and mild exanthema on his arms. He had a one-week history of coughing and fever. Thorough microbiological investigations were implemented. After a few days both the IgM titre and polymerase chain reaction investigations for M. pneumonia from a throat swab taken on admission proved to be positive. Treatment with doxycycline resulted in rapid improvement in clinical condition. All mucosal lesions almost healed within two weeks. CONCLUSION: M. pneumonia infections may be associated with the triad of stomatitis, conjunctivitis and urethritis in the absence of extensive skin manifestations. The prognosis is favourable.

Prolonged decrease of CD4+ T lymphocytes in HIV-1-infected patients after radiotherapy for a solid tumor.

BACKGROUND: In HIV-negative patients, radiotherapy (RT) decreases CD4 T-cell counts. We studied the effects of RT in HIV-1 positive patients. METHODS: HIV-1 positive patients with a subsequent diagnosis of a solid tumor were selected from the Dutch national observational HIV cohort, Aids Therapy Evaluation in the Netherlands (ATHENA). The patients were grouped according to whether they had received RT or not. Primary endpoint of the study was the time from baseline to reaching CD4 cell counts higher than those at baseline. Kaplan-Meier estimates of the percentage of patients reaching the endpoint were calculated. RESULTS: Ninety patients were included of whom 36 received RT and 54 did not. Median duration of RT was 46 [interquartile range (IQR) 30-63] days. Median first CD4 cell count after stopping RT was 150 (IQR 30-270) × 10/L lower compared with baseline. In 13 of the 36 patients receiving RT, CD4 cell counts recovered to baseline, after a median of 469 (IQR 345-595) days. In 35 of the 54 patients without RT, the CD4 cell count recovered to baseline or higher, after a median of 112 (IQR 42-182) days. After 3 years, in 39% of patients who had RT compared with 71% of patients without RT, CD4 cell counts recovered to baseline or higher (P < 0.0001). In a Cox regression adjusted for potential confounders, RT was associated with a longer (hazard ratio 0.29; 95% confidence interval 0.13 to 0.63) and combination antiretroviral therapy use with a shorter time to return to baseline [hazard ratio 2.46 (95% confidence interval 1.11 to 5.48)]. CONCLUSIONS: RT resulted in a significant and prolonged decrease in CD4 cell counts.

Two cases of Plasmodium falciparum malaria in the Netherlands without recent travel to a malaria-endemic country.

Recently, two patients of African origin were given a diagnosis of Plasmodium falciparum malaria without recent travel to a malaria-endemic country. This observation highlights the importance for clinicians to consider tropical malaria in patients with fever. Possible transmission routes of P. falciparum to these patients will be discussed. From a public health perspective, international collaboration is crucial when potential cases of European autochthonous P. falciparum malaria in Europe re considered.

Effects of chlorhexidine oral decontamination on respiratory colonization during mechanical ventilation in intensive care unit patients.

We conducted a retrospective cohort study to assess respiratory colonization before and after the use of chlorhexidine oral decontamination among a cohort of intensive care unit patients who received mechanical ventilation. We observed a decrease in the prevalence of Enterobacteriaceae and an increase in the incidence of fungal colonization. Chlorhexidine oral decontamination might have a differential effect on respiratory colonization.