Humoral and cellular responses to mRNA-based COVID-19 booster vaccinations in patients with solid neoplasms under active treatment.

BACKGROUND: Patients with cancer are at high risk for severe coronavirus disease 2019 (COVID-19) infection. Knowledge regarding the efficacy of the messenger RNA (mRNA) vaccines in actively treated cancer patients is limited as they had been excluded from the pivotal studies of these vaccines. We evaluated humoral and cellular immune responses in cancer patients after double vaccination and a booster dose and identified disease- and treatment-related factors associated with a reduced immune response. We also documented the number and outcome of breakthrough infections. PATIENTS AND METHODS: Patients with metastatic solid malignancies undergoing active treatment were included if they had received two doses of the severe acute respiratory syndrome coronavirus 2 mRNA vaccines BNT162b2 or mRNA-1273 and a booster dose. Other causes of immunosuppression and previous COVID-19 infections (positive anti-nucleocapsid titers) were exclusion criteria. Anti-spike antibodies, neutralizing antibodies (nAbs) and T-cell responses were assessed about 6 months after the two-dose vaccination and 4 weeks after the booster. RESULTS: Fifty-one patients had pre-booster and 46 post-booster measurements. Anti-spike titers after two vaccine doses were highly variable and significantly lower in older patients, during treatment with chemotherapy compared to targeted and endocrine treatments and in patients with low CD4+ or CD19+ cell counts. The booster dose led to a significant increase in anti-spike antibodies and nAbs, achieving almost uniformly high titers, irrespective of baseline and treatment factors. The cellular immune response was also significantly increased by the booster, however generally more stable and not influenced by baseline factors and treatment type. Seventeen patients (33%) experienced breakthrough infections, but none required hospital care or died from COVID-19. CONCLUSIONS: An mRNA vaccine booster dose is able to increase humoral and cellular immune responses and to overcome the immunosuppressive influence of baseline and treatment factors in cancer patients. Breakthrough infections were uniformly mild in this vaccinated high-risk population.

[Management of Adult Community-Acquired Pneumonia and Prevention - Update 2021 - Guideline of the German Respiratory Society (DGP), the Paul-Ehrlich-Society for Chemotherapy (PEG), the German Society for Infectious Diseases (DGI), the German Society of Medical Intensive Care and Emergency Medicine (DGIIN), the German Viological Society (DGV), the Competence Network CAPNETZ, the German College of General Practitioneers and Family Physicians (DEGAM), the German Society for Geriatric Medicine (DGG), the German Palliative Society (DGP), the Austrian Society of Pneumology Society (ÖGP), the Austrian Society for Infectious and Tropical Diseases (ÖGIT), the Swiss Respiratory Society (SGP) and the Swiss Society for Infectious Diseases Society (SSI)]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie ­ Update 2021.

The present guideline provides a new and updated concept of the management of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2016.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment.The recommendations aim at the same time at a structured assessment of risk for adverse outcome as well as an early determination of treatment goals in order to reduce mortality in patients with curative treatment goal and to provide palliation for patients with treatment restrictions.

Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie: update 2021

Die vorliegende Leitlinie umfasst ein aktualisiertes Konzept der Behandlung und Prävention von erwachsenen Patienten mit ambulant erworbener Pneumonie und löst die bisherige Leitlinie aus dem Jahre 2016 ab. Sie wurde entsprechend den Maßgaben zur Methodologie einer S3-Leitlinie erarbeitet und verabschiedet. Hierzu gehören eine systematische Literaturrecherche und -bewertung, die strukturierte Diskussion der aus der Literatur begründbaren Empfehlungen sowie eine Offenlegung und Bewertung möglicher Interessenskonflikte. Die Leitlinie zeichnet sich aus durch eine Zentrierung auf definierte klinische Situationen, eine aktualisierte Maßgabe der Schweregradbestimmung sowie Empfehlungen zu einer individualisierten Auswahl der initialen antimikrobiellen Therapie. Die Empfehlungen zielen gleichzeitig auf eine strukturierte Risikoevaluation als auch auf eine frühzeitige Bestimmung des Therapieziels, um einerseits bei kurativem Therapieziel die Letalität der Erkrankung zu reduzieren, andererseits bei palliativem Therapieziel eine palliative Therapie zu eröffnen.

The present guideline provides a new and updated concept of the management of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2016.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment.The recommendations aim at the same time at a structured assessment of risk for adverse outcome as well as an early determination of treatment goals in order to reduce mortality in patients with curative treatment goal and to provide palliation for patients with treatment restrictions.

Acute respiratory distress syndrome during the COVID-19 pandemic: not only SARS-CoV-2.

A previously healthy 30-year-old woman developed severe ARDS at the beginning of the COVID-19 pandemic. SARS-CoV-2 infection was suspected, but testing was negative. Mycoplasma pneumoniae was detected by PCR in bronchoalveolar lavage fluid and blood. This case illustrates that M. pneumoniae infection can progress to septicemia and ARDS with severe respiratory failure in young healthy adults.

Antibiotic-resistant pathogens in different patient settings and identification of surveillance gaps in Switzerland - a systematic review.

The prevalence of antimicrobial resistance (AMR) varies significantly among different patient populations. We aimed to summarise AMR prevalence data from screening studies in different patient settings in Switzerland and to identify surveillance gaps. We performed a systematic review, searching Pubmed, MEDLINE, Embase (01/2000-05/2017) and conference proceedings for Swiss studies reporting on carbapenemase-producing Enterobacteriaceae (CPE), extended-spectrum beta-lactamases (ESBL), mobilised colistin-resistance, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) within different patient settings. We identified 2345 references and included 46 studies. For acute care patients, most screening data come from admission screenings, whereas AMR prevalence among hospitalised patients is largely unknown. Universal admission screenings showed ESBL-prevalences of 5-8% and MRSA-prevalences of 2-5%. For targeted screening, ESBL-prevalence ranged from 14-21%; MRSA-prevalence from 1-4%. For refugees, high ESBL (9-24%) and MRSA (16-24%) carriage rates were reported; returning travellers were frequently (68-80%) colonised with ESBL. Screening data for other pathogens, long-term care facility (LTCF) residents and pediatric populations were scarce. This review confirms high ESBL- and MRSA-carriage rates for risk populations in Switzerland. Emerging pathogens (CPE and VRE) and certain populations (inpatients, LTCF residents and children) are understudied. We encourage epidemiologists and public health authorities to consider these findings in the planning of future surveillance studies.

Pulmonary actinomycosis and Hodgkin's disease: when FDG-PET may be misleading.

We present a patient with advanced Hodgkin's disease treated with escalated BEACOPP chemotherapy. The result from the interim fluorodeoxyglucose positron emission tomography with CT (PET-CT) after two cycles of chemotherapy is crucial for treatment guidance for the clinical trial HD18 from the German Hodgkin Study Group. An increase in size and standard uptake value (SUV) of a pulmonary lesion suggesting refractory Hodgkin's disease was documented. Since all other manifestations of the lymphoma responded well to the treatment, the discordant behaviour was suspicious for another reason for this progressive pulmonary lesion. Bronchoscopy revealed Actinomyces species in cultures from bronchial washings. Specific treatment was initiated and consisted of 2 weeks of intravenous penicillin followed by ceftriaxone intravenous for another 4 weeks and subsequent oral amoxicillin to complete 12 months of antibiotic therapy. For the Hodgkin's lymphoma, complete remission was documented after a total of six cycles of escalated BEACOPP.

The potential impact of biomarker-guided triage decisions for patients with urinary tract infections.

OBJECTIVES: Current guidelines provide limited evidence as to which patients with urinary tract infection (UTI) require hospitalisation. We evaluated the currently used triage routine and tested whether a set of criteria including biomarkers like proadrenomedullin (proADM) and urea have the potential to improve triage decisions. METHODS: Consecutive adults with UTI presenting to our emergency department (ED) were recruited and followed for 30 days. We defined three virtual triage algorithms, which included either guideline-based clinical criteria, optimised admission proADM or urea levels in addition to a set of clinical criteria. We compared actual treatment sites and observed adverse events based on the physician judgment with the proportion of patients assigned to treatment sites according to the three virtual algorithms. Adverse outcome was defined as transfer to the intensive care unit (ICU), death, recurrence of UTI or rehospitalisation for any reason. RESULTS: We recruited 127 patients (age 61.8 ± 20.8 years; 73.2 % females) and analysed the data of 123 patients with a final diagnosis of UTI. Of these 123 patients, 27 (22.0 %) were treated as outpatients. Virtual triage based only on clinical signs would have treated only 22 (17.9 %) patients as outpatients, with higher proportions of outpatients equally in both biomarker groups (29.3 %; p = 0.02). There were no significant differences in adverse events between outpatients according to the clinical (4.5 %), proADM (2.8 %) or urea groups (2.8 %). The mean length of stay was 6.6 days, including 2.2 days after reaching medical stability. CONCLUSIONS: Adding biomarkers to clinical criteria has the potential to improve risk-based triage without impairing safety. Current rates of admission and length of stay could be shortened in patients with UTI.

Influence of procalcitonin on decision to start antibiotic treatment in patients with a lower respiratory tract infection: insight from the observational multicentric ProREAL surveillance.

Procalcitonin (PCT)-guided antibiotic stewardship is a successful strategy to decrease antibiotic use. We assessed if clinical judgement affected compliance with a PCT-algorithm for antibiotic prescribing in a multicenter surveillance of patients with lower respiratory tract infections (LRTI). Initiation and duration of antibiotic therapy, adherence to a PCT algorithm and outcome were monitored in consecutive adults with LRTI who were enrolled in a prospective observational quality control. We correlated initial clinical judgment of the treating physician with algorithm compliance and assessed the influence of PCT on the final decision to initiate antibiotic therapy. PCT levels correlated with physicians' estimates of the likelihood of bacterial infection (p for trend <0.02). PCT influenced the post-test probability of antibiotic initiation with a greater effect in patients with non-pneumonia LRTI (e.g., for bronchitis: -23 % if PCT ≤ 0.25 µg/L and +31 % if PCT > 0.25 µg/L), in European centers (e.g., in France -22 % if PCT ≤ 0.25 µg/L and +13 % if PCT > 0.25 µg/L) and in centers, which had previous experience with the PCT-algorithm (-16 % if PCT ≤ 0.25 µg/L and +19 % if PCT > 0.25 µg/L). Algorithm non-compliance, i.e. antibiotic prescribing despite low PCT-levels, was independently predicted by the likelihood of a bacterial infection as judged by the treating physician. Compliance was significantly associated with identification of a bacterial etiology (p = 0.01). Compliance with PCT-guided antibiotic stewardship was affected by geographically and culturally-influenced subjective clinical judgment. Initiation of antibiotic therapy was altered by PCT levels. Differential compliance with antibiotic stewardship efforts contributes to geographical differences in antibiotic prescribing habits and potentially influences antibiotic resistance rates.

Community-onset Staphylococcus aureus bacteraemia in hospitalised African children: high incidence in HIV-infected children and high prevalence of multidrug resistance.

BACKGROUND: Invasive bacterial disease causes significant morbidity and mortality in children in developing countries. The burden of invasive disease caused by Staphylococcus aureus and S. aureus antimicrobial resistance patterns in African children in settings with a high prevalence of HIV infection remain ill-defined. AIMS AND OBJECTIVES: To describe the burden of community-onset bacteraemic S. aureus infections in children in an area with a high prevalence of paediatric HIV infection, and to describe the antimicrobial resistance patterns. METHODS: A retrospective record review of children hospitalised at Chris Hani Baragwanath Hospital, Soweto, with S. aureus bacteraemia between January 2005 and December 2006 was conducted. Community-onset S. aureus bloodstream infections were defined as S. aureus cultured from blood obtained within 48 hours of admission. RESULTS: Community-onset S. aureus bacteraemia was identified in 161 children, representing an incidence of 26/100,000, with 63 (39%) isolates identified as methicillin-resistant (10/100,000). The incidence of community-onset S. aureus bacteraemia, both methicillin-susceptible and methicillin-resistant, was inversely related to age and greater in HIV-infected than uninfected children. High rates of antibiotic resistance were observed in MRSA isolates and only resistance to amikacin, fusidic acid and ciprofloxacin was <40%. MRSA isolates were frequently multidrug-resistant. Among HIV-infected children, resistance to trimethoprim-sulfamethoxazole was 100% and to rifampicin was 78%. CONCLUSIONS: This study highlights the burden of S. aureus bacteraemia in a setting with a high prevalence of paediatric HIV infection. The high incidence of S. aureus bacteraemia coupled with a high prevalence of methicillin resistance, particularly in HIV-infected children, needs to be considered in the empirical management of paediatric sepsis in settings such as ours.

Use of a rapid test of pneumococcal colonization density to diagnose pneumococcal pneumonia.

BACKGROUND: There is major need for a more sensitive assay for the diagnosis of pneumococcal community-acquired pneumonia (CAP). We hypothesized that pneumococcal nasopharyngeal (NP) proliferation may lead to microaspiration followed by pneumonia. We therefore tested a quantitative lytA real-time polymerase chain reaction (rtPCR) on NP swab samples from patients with pneumonia and controls. METHODS: In the absence of a sensitive reference standard, a composite diagnostic standard for pneumococcal pneumonia was considered positive in South African human immunodeficiency virus (HIV)-infected adults hospitalized with radiographically confirmed CAP, if blood culture, induced good-quality sputum culture, Gram stain, or urinary Binax demonstrated pneumococci. Results of quantitative lytA rtPCR in NP swab samples were compared with quantitative colony counts in patients with CAP and 300 HIV-infected asymptomatic controls. RESULTS: Pneumococci were the leading pathogen identified in 76 of 280 patients with CAP (27.1%) using the composite diagnostic standard. NP colonization density measured by lytA rtPCR correlated with quantitative cultures (r = 0.67; P < .001). The mean lytA rtPCR copy number in patients with pneumococcal pneumonia was 6.0 log(10) copies/mL, compared with patients with CAP outside the composite standard (2.7 log(10) copies/mL; P < .001) and asymptomatic controls (0.8 log(10) copies/mL; P < .001). A lytA rtPCR density ≥8000 copies/mL had a sensitivity of 82.2% and a specificity of 92.0% for distinguishing pneumococcal CAP from asymptomatic colonization. The proportion of CAP cases attributable to pneumococcus increased from 27.1% to 52.5% using that cutoff. CONCLUSIONS: A rapid molecular assay of NP pneumococcal density performed on an easily available specimen may significantly increase pneumococcal pneumonia diagnoses in adults.

Optimised patient transfer using an innovative multidisciplinary assessment in Kanton Aargau (OPTIMA I): an observational survey in lower respiratory tract infections.

BACKGROUND: Current medical scores have limited efficiency and safety profiles to enable assignment to the most appropriate treatment site in patients with lower respiratory tract infections (LRTIs). We describe our current triage practice and assess the potential of a combination of CURB65 with proadrenomedullin (ProADM) levels for triage decisions. METHODS: Consecutive patients with LRTIs presenting to our emergency department were prospectively followed and retrospectively classified according to CURB65 and ProADM levels (CURB65-A). Low medical risk patients were further subgrouped according to biopsychosocial and functional risks. We compared the proportion of patients virtually allocated to triage sites with actual triage decisions and assessed the added impact of ProADM in a subgroup. RESULTS: Overall, 93% of 146 patients were hospitalised. Among the 138 patients with available CURB65-A, 17.4% had a low medical risk indicating possible treatment in an outpatient or non-acute medical setting; 34.1% had an intermediate medical risk (short-hospitalisation); and 48.6% had a high medical risk (hospitalisation). Fewer patients were in a low CURB65-A class (I) than a low CURB65 class (0,1) (17.4% vs. 46.3%, p <0.001). Mean length of hospitalisation was 9.8 days including 3.6 days after reaching medical stability. In 60.3% of patients, hospitalisation was prolonged after medical stability mainly for medical reasons. CONCLUSIONS: Current rates of hospitalisation are high in patients with LRTI and length of stay frequently extended beyond time of medical stabilization. The lower proportion of patients reclassified as low risk by adding ProADM to the CURB65 score might improve confidence in the triage algorithm.

A rare cause of pulmonary infiltrates one should be aware of: a case of daptomycin-induced acute eosinophilic pneumonia.

We report a 69-year-old patient who developed fever and dyspnea 3 weeks after the initiation of daptomycin therapy for spondylodiscitis with lumbar epidural and bilateral psoas abscesses due to ampicillin- and high-level-gentamicin-resistant Enterococcus faecium. There was profound hypoxia and the chest X-ray showed extensive patchy infiltrates bilaterally. A bronchoalveolar lavage revealed 30% eosinophils and results of microbiological studies were normal. Daptomycin-induced eosinophilic pneumonia was diagnosed and the patient rapidly improved after the discontinuation of daptomycin and a brief course of prednisone. Increased attention must be paid to this rare but serious side effect of daptomycin.

Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey.

All published evidence on procalcitonin (PCT)-guided antibiotic therapy was obtained in trials where physicians knew that they were being monitored, possibly resulting in higher adherence to the PCT algorithm. This study investigates the effectiveness of PCT guidance in an observational quality control survey. We monitored antibiotic therapy and algorithm adherence in consecutive patients with respiratory tract infections admitted to the Kantonsspital Aarau, Switzerland, between May 2008 and February 2009. The results were compared to the site-specific results of the former ProHOSP study. Overall and more pronounced for patients with community-acquired pneumonia, the median duration of antibiotic treatment in this survey was shorter than the ProHOSP control patients (6 vs. 7 days, P = 0.048 and 7 vs. 9 days, P < 0.001). In 72.5% of patients, antibiotics were administered according to the prespecified PCT algorithm. No significant differences concerning adverse medical outcome could be detected. This study mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of trial conditions. If algorithm adherence is reinforced, antibiotic exposure can be markedly reduced with subsequent reduction of antibiotic-associated side effects and antibiotic resistance. The integration of the PCT algorithm into daily practice requires ongoing reinforcement and involves a learning process of the prescribing physicians.

Changing characteristics of invasive pneumococcal disease in Metropolitan Atlanta, Georgia, after introduction of a 7-valent pneumococcal conjugate vaccine.

BACKGROUND: The rate of invasive pneumococcal disease (IPD) has decreased among both immunized children and nonimmunized adults since the licensure of a heptavalent pneumococcal conjugate vaccine (PCV7) for use in infants in the United States in 2000. METHODS: Temporal trends in IPD incidence, clinical syndromes, and underlying conditions were analyzed using active laboratory- and population-based surveillance data from the Centers for Disease Control and Prevention-sponsored Georgia Emerging Infections Program for the 20-county Metropolitan Atlanta, Georgia, for the period of July 1997 through June 2004. P values were determined by test for trend. RESULTS: Since 2000, there have been significant decreases in the rates of invasive pneumococcal pneumonia (relative risk [RR], 0.80; P=.002) and meningitis (RR, 0.41; P=.003) in adults and for primary bacteremia, invasive pneumonia, and meningitis in children (RR, 0.16 [P<.001], 0.60 [P=.003], and 0.70 [P=.009], respectively). Among human immunodeficiency virus-infected persons, there were significant decreases in the overall rates of IPD (decrease of 43%; P<.001) and invasive pneumonia (decrease of 44%; P<.001) since 2000-2001, although the rate of IPD increased significantly (increase of 53%; P=.022) among patients with acquired immunodeficiency syndrome. There was a concurrent increase in the proportion of adults aged > or = 40 years with underlying comorbidities. Rates of non-PCV7 serotypes increased 1.61-fold and 1.28-fold from 2000-2001 to 2003-2004 in children and adults (P=.005 for both). CONCLUSIONS: The decreasing incidence of IPD in Atlanta since 2000-2001 was associated with decreases in cases of pneumonia and meningitis in adult and pediatric subjects and in cases of primary bacteremia in children. The burden of serotype-replacement disease remained small. Adults with comorbidities represent a growing proportion of patients with IPD.

The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn and trauma.

Patients with systemic inflammatory response syndrome (SIRS) and sepsis exhibit decreased plasma selenium and glutathione peroxidase activity. This has been shown in several clinical studies. Moreover, the degree of selenium deficiency correlates with the severity of the disease and the incidence of mortality. Patients with SIRS and sepsis are exposed to severe oxidative stress. Selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and are involved in the regulation of inflammatory processes. Therefore, selenium substitution in those patients might be effective in the prevention of multiorgan failure. The results of randomised clinical trials investigating selenium substitution in critical ill patients with inflammation are reviewed. In two independently performed randomised, prospective clinical trials, including patients with systemic inflammatory response syndrome or sepsis, the supplementation of selenium revealed a significant reduction in multiorgan failure and, especially, a lower incidence of acute renal failure and respiratory distress syndrome. One of those trials also could demonstrate a significant reduction of mortality in the most severely ill patients. Two other studies, where selenium together with other trace elements or a mixture of antioxidants were used in the treatment of patients with severe burn injuries or trauma showed a significant reduction in the secondary infection rate, including sepsis. Thus, selenium supplementation seems to improve the outcome of patients with SIRS, sepsis and severe injury, however, pivotal prospective clinical trials with sufficient statistical power are now necessary to finally prove the efficacy of a selenium supplementation in these diseases.

Control of multiply resistant cocci: do international comparisons help?

Antibiotic resistance has become a worldwide problem. However, the reasons for the uneven geographic distribution of antibiotic-resistant microorganisms are not fully understood. For instance, there are striking differences in the epidemiology of multiresistant gram-positive cocci between the USA and Germany. According to recent reports, the prevalence of high-level penicillin-resistant pneumococci (PRP), meticillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in clinically relevant isolates of hospitalised patients in the USA and Germany are: PRP, 14% versus less than 1%; MRSA, 36% versus 15%; and VRE, 15% versus 1%. These disparities may be explained by several determinants: (1) diagnostic practice and laboratory recognition (all three pathogens); (2) clonal differences and pathogen transmissibility (VRE); (3) antibiotic prescribing practices (all three pathogens); (4) population characteristics, including extensive daycare exposure in the USA (PRP); (5) cultural factors (all three pathogens); (6) factors related to the health-care and legal system (all three pathogens); and (7) infection-control practices (MRSA and VRE). Understanding these determinants is important for preventing further spread of multiresistant cocci within the USA. A rational approach to national surveillance is urgently needed in Germany to preserve the favourable situation and decrease MRSA transmission. Finally, we suggest that a macro-level perspective on antibiotic resistance can broaden the understanding of this worldwide calamity, and help prevent further dissemination of multiply resistant microorganisms.

Drug resistance in intensive care units.

Intensive care units (ICUs) are generally considered epicenters of antibiotic resistance and the principal sources of outbreaks of multi-resistant bacteria. The most important risk factors are obvious, such as excessive consumption of antibiotics exerting selective pressure on bacteria, the frequent use of invasive devices and relative density of a susceptible patient population with severe underlying diseases. Infections due to antibiotic-resistant bacteria have a major impact on morbidity and health-care costs. Increased mortality is not uniformly shown for all of these organisms: Methicillin-resistant Staphylococcus aureus (MRSA) seems to cause significantly higher mortality, in contrast to vancomycin-resistant enterococci (VRE). Therefore it is essential to diminish these potential risk factors, especially by providing locally adapted guidelines for the prudent use of antibiotic therapy. A quality control of antimicrobial therapy within a hospital, and especially within the ICU, might help to minimize the selection of multidrug-resistant bacteria. The restricted use of antimicrobial agents in prophylaxis and therapy has also been shown to have at least temporal effects on local resistance patterns. New approaches to the problem of drug resistance in ICUs are badly needed.