Management of Patients with Suspected or Confirmed Antibiotic Allergy: Executive Summary of Guidelines from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Allergy and Clinical Immunology (SEAIC), the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Intensive Medicine and Coronary Care Units (SEMICYUC).

Suspected or confirmed antibiotic allergy is a frequent clinical circumstance that influences antimicrobial prescription and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs in several countries. These guidelines aim to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. An expert panel (11 members of various scientific societies) formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence, and formulated graded recommendations when possible. The answers to all the questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy was recommended to improve antibiotic selection and, consequently, clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ß-lactam allergy were formulated, as were recommendations on the implementation and monitoring of the impact of the guidelines. Antimicrobial stewardship programs and allergists should design and implement activities that facilitate the most appropriate use of antibiotics in these patients.

Intestinal persistence of a plasmid harbouring the OXA-48 carbapenemase gene after hospital discharge.

To study intestinal colonization by OXA-48-producing Klebsiella pneumoniae (KpO48) after hospital discharge, stool samples from 22 previously colonized subjects were collected. Time from discharge was 33-611 days, without readmissions. Eight subjects (36%) were identified as blaOXA-48 gene carriers. In all of them the hospital-acquired strain of KpO48 had been lost, and the gene was harboured by other strains of K. pneumoniae, Klebsiella oxytoca and/or Escherichia coli. Our findings show intestinal persistence for several months of a plasmid harbouring the OXA-48 carbapenemase gene in a significant proportion of individuals in the absence of antibiotic treatment.

Epidemiology and control measures of an OXA-48-producing Enterobacteriaceae hospital-wide oligoclonal outbreak.

The main objective of our study was to describe the epidemiological and microbiological features of an oligoclonal hospital-wide outbreak caused by OXA-48-producing Enterobacteriaceae (OXA-48-PE). OXA-48 is a carbapenemase belonging to Ambler class D beta-lactamases, identified frequently in the Mediterranean and Southern European countries, and associated with several Enterobacteriaceae species. An outbreak of OXA-48-PE with a complex epidemic pattern was detected in January 2011. Initial control measures included contact precautions and the reinforcement of infection control practices, but despite all efforts made, the epidemiological situation hardly changed and new measures were implemented during 2013. An observational retrospective study was performed to describe the main features of the outbreak and to analyse the cumulative incidence (CI) trends. Eight hundred and 16 patients colonised or infected by OXA-48-PE were identified during the 2-year period (January 2013-December 2014), female 46%, mean age (s.d.), 71.6 (15.2). The samples isolated in the incident cases were rectal swabs (80%), urine samples (10.7%), blood samples (2.8%) and other clinical samples (6.6%). The most frequent OXA-48-PE was Klebsiella pneumoniae. Eleven different clones were identified, but K. pneumoniae sequence types 11 and 405 were predominant: ST11 (64.2%) and ST405 (29.3%). OXA-48-PE CI trend suffered a statistically significant change in August 2013, which continued the following months. Though we could not eradicate the outbreak, we observed a statistically significant drop in CI after an intervention for OXA-48-PE control, based on patient cohort, active surveillance, electronic alerts and reinforcement of infection control measures in a tertiary hospital.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Optimizing antimicrobial prescribing: a practical decalogue.

Increasing antibiotic resistance is one of the leading problems in the Public Agenda worldwide. In the last 20 years, the pace of antimicrobial drug development has markedly slowed leading to a dramatic world situation. Infections with antibiotic-resistant microorganisms have been associated with increased length of stay, mortality and costs. Improving antimicrobial prescribing is one of the tools in our hands to optimize the outcomes of patients with moderate to severe infections and control the emerging of resistance. Several clues to improve antimicrobial prescribing are provided as a key-messages decalogue.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Opportunities to improve antimicrobial use in paediatric intensive care units: a nationwide survey in Spain.

Improving antimicrobial use is a complex process that requires an accurate assessment of ongoing problems and barriers. Paediatric intensive care units (PICU) have seldom been assessed from this perspective. Two Internet-based, self-administered surveys were conducted nationwide in Spain between January and February 2014. The first survey aimed to assess those characteristics of Spanish PICUs that could influence antimicrobial prescribing or antimicrobial stewardship. The second survey targeted Spanish PICU physicians and pursued to assess their attitudes and perceptions regarding antimicrobial resistance and antimicrobial use. Information about 29/39 contacted PICUs was obtained. A total of 114/206 (55.3%) paediatric intensivists responded. PICUs were heterogeneous regarding years since foundation, number of beds, type of patients admitted and staffing. Only 11 (37.9%) PICUs had available e-prescribing systems. Procalcitonin was available in 24 (89.1%) PICUs, but there were no procalcitonin-based protocols in 14 (60.9%) of them. Half of surveyed PICUs had implemented antimicrobial stewardship activities. Ninety-eight of the 114 PICU physicians (86%) who participated considered that antimicrobial resistance was a significantly relevant problem for their daily and that improving antimicrobial use in their PICU should be a priority (103; 90.4%). The main perceived problems regarding antimicrobial use were the excessive use of antimicrobials in patients with nonconfirmed infections and excessive use of broad-spectrum antimicrobials. The most valued antimicrobial stewardship interventions were the implementation of protocols to guide antimicrobial therapy. Spanish PICU doctors are aware of the relevance of the problem of antimicrobial resistance and the need to improve antimicrobial use. Targeted interventions should take into account their difficulties and preferences when feasible.

How do physicians cope with controversial topics in existing guidelines for the management of infective endocarditis? Results of an international survey.

International guidelines are available to help physicians prescribe appropriate antibiotic regimens to patients with infective endocarditis (IE). However some topics of these guidelines are controversial. We conducted an international survey to assess physicians' adherence to these guidelines, focusing on these controversial items. An invitation to participate to a 15-question online survey was sent in 2012-2013 to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members, scientific societies and corresponding authors of publications on IE mentioned in PubMed from 1990 to 2012, inclusive. Eight hundred thirty-seven physicians participated in the survey, and 625 (74.7%) completed it over the first question. The results showed great heterogeneity of practices. Claiming to follow guidelines was marginally associated with more guideline-based strategies. Gentamicin use depended on causative pathogens (p <0.001) and physician specialty (p 0.02). Eighty-six per cent of the physicians favoured vancomycin alone or in combination with gentamicin or rifampicin as a first-line treatment for left-sided native valve methicillin-resistant Staphylococcus aureus IE, 31% considered switching to oral therapy as a therapeutic option and 33% used the ampicillin and ceftriaxone combination for enterococcal IE as a first-line therapy. Physician specialty significantly affected the choice of a therapeutic strategy, while practicing in a university hospital or the number of years of practice had virtually no impact. Our survey, the largest on IE treatment, underscores important heterogeneity in practices for treatment of IE. Nonetheless, physicians who do not follow guidelines can have rational strategies that are based on the literature. These results could inform the revision of future guidelines and identify unmet needs for future studies.

[Respiratory viriasis. Influenza]. / Viriasis respiratorias. Gripe.

Respiratory viriasis are acute infectious diseases with a usually favorable course. Influenza is the disease caused by influenza viruses A and B; it could cause seasonal periodical epidemics and influenza A is implicated in worlwide pandemias. Influenza complications usually are limited to older patients and to those with comorbilities, especially those with chronic respiratory or cardiovascular diseases. Anti-influenza therapy has an effect on the duration of the symptomatic period and vaccination efficiently decreases the incidence of the infection. Respiratory syncytial virus is the more frequent cause of the acute bronchiolitis in breastfeeding patients. Rinovirus and coronavirus are implicated in the common cold. Coronavirus was the etiological agent of the severe acute respiratory syndrome, described in 2002 in China. Parainfluenza virus is the cause of the laryngeal croup in infants.

Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge.

Bacteraemia due to carbapenemase-producing Enterobacteriaceae is an emerging medical problem. Management of this entity is complicated by the difficulty in identifying resistance patterns and the limited therapeutic options. A cohort study was performed including all episodes of bloodstream infection due to OXA-48-producing Enterobacteriaceae (O48PE), occurring between July 2010 and April 2012. Data on predisposing factors, clinical presentation, therapy and outcome were collected from medical records. There were 40 cases of bacteraemia caused by O48PE, 35 Klebsiella pneumoniae and five Escherichia coli. Patients were elderly with significant comorbidities (57.5% underlying malignancy). Thirty-five cases (87.5%) were nosocomial, and five (12.5%) were healthcare-associated. Patients had frequently been exposed to antibiotics and to invasive procedures during hospitalization. The most common source of bacteraemia was the urinary tract followed by deep intra-abdominal surgical site infection. Clinical presentation was severe sepsis or shock in 18 cases (45%). Extended-spectrum ß-lactamase production was detected in 92.5% of isolates. MIC(90) for ertapenem, imipenem and meropenem were 32, 16 and 16 mg/L, respectively. Most frequently preserved antibiotics were amikacin, colistin, tigecycline and fosfomycin. These antibiotics combined are the basis of targeted therapies, including carbapenem in selected cases. Median delay in starting clinically adequate and microbiologically appropriate treatment was 3 days. Crude mortality during admission and within 30 days from bacteraemia was 65% and 50%, respectively. Bloodstream infections caused by O48PE have a poor prognosis. Delay in diagnosis and in initiation of optimal antimicrobial therapy is frequent. Suspicion and rapid identification could contribute to improving outcomes.

Changes in epidemiology, clinical features and severity of influenza A (H1N1) 2009 pneumonia in the first post-pandemic influenza season.

Although the influenza A (H1N1) 2009 virus is expected to circulate as a seasonal virus for some years after the pandemic period, its behaviour cannot be predicted. We analysed a prospective cohort study of hospitalized adults with influenza A (H1N1) 2009 pneumonia at 14 teaching hospitals in Spain to compare the epidemiology, clinical features and outcomes of influenza A (H1N1) 2009 pneumonia between the pandemic period and the first post-pandemic influenza season. A total of 348 patients were included: 234 during the pandemic period and 114 during the first post-pandemic influenza season. Patients during the post-pandemic period were older and more likely to have chronic obstructive pulmonary disease, chronic kidney disease and cancer than the others. Septic shock, altered mental status and respiratory failure on arrival at hospital were significantly more common during the post-pandemic period. Time from illness onset to receipt of antiviral therapy was also longer during this period. Early antiviral therapy was less frequently administered to patients during the post-pandemic period (22.9% versus 10.9%; p 0.009). In addition, length of stay was longer, and need for mechanical ventilation and intensive-care unit admission were significantly higher during the post-pandemic period. In-hospital mortality (5.1% versus 21.2%; p <0.001) was also greater during this period. In conclusion, significant epidemiological changes and an increased severity of influenza A (H1N1) 2009 pneumonia were found in the first post-pandemic influenza season. Physicians should consider influenza A (H1N1) 2009 when selecting microbiological testing and treatment in patients with pneumonia in the upcoming influenza season.

Immunosuppressed patients with pandemic influenza A 2009 (H1N1) virus infection.

The purpose of this paper was to prospectively characterize the clinical manifestations and outcomes of confirmed influenza A 2009 (H1N1) virus infection in immunosuppressed patients with hospital admission and compare them with those of a general population. A multicenter prospective cohort study was carried out. All adult patients admitted to 13 hospitals in Spain with confirmed influenza A 2009 (H1N1) virus infection from June 12, 2009 to November 11, 2009 were included. Risk factors for complicated influenza infection were studied in immunosuppressed patients. Overall, 559 patients were included, of which 56 were immunosuppressed, nine with solid or hematological malignancies, 18 with solid-organ transplant recipients, 13 with corticosteroid therapy, and six with other types of immunosuppression. Clinical findings at diagnosis were similar in both groups. Nineteen immunosuppressed patients had pneumonia (33.9%). Immunosuppressed patients with pandemic influenza had bacterial co-infection more frequently (17.9% vs. 6.4%, p = 0.02), specifically, gram-negative bacilli and Staphylococcus aureus infections. Mortality was higher in immunosuppressed patients (7.1% vs. 1.8%, p < 0.05). The only modifiable risk factor of complicated influenza A 2009 (H1N1) was delayed antiviral therapy. In immunosuppressed patients, influenza A 2009 (H1N1) virus infection has higher mortality than in non-immunosuppressed individuals. Bacterial co-infection is common in complicated cases.

[Programs for optimizing the use of antibiotics (PROA) in Spanish hospitals: GEIH-SEIMC, SEFH and SEMPSPH consensus document]. / Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH.

The antimicrobial agents are unique drugs for several reasons. First, their efficacy is higher than other drugs in terms of reduction of morbidity and mortality. Also, antibiotics are the only group of drugs associated with ecological effects, because their administration may contribute to the emergence and spread of microbial resistance. Finally, they are used by almost all medical specialties. Appropriate use of antimicrobials is very complex because of the important advances in the management of infectious diseases and the spread of antibiotic resistance. Thus, the implementation of programs for optimizing the use of antibiotics in hospitals (called PROA in this document) is necessary. This consensus document defines the objectives of the PROA (namely, to improve the clinical results of patients with infections, to minimise the adverse events associated to the use of antimicrobials including the emergence and spread of antibiotic resistance, and to ensure the use of the most cost-efficacious treatments), and provides recommendations for the implementation of these programs in Spanish hospitals. The key aspects of the recommendations are as follows. Multidisciplinary antibiotic teams should be formed, under the auspices of the Infection Committees. The PROA need to be considered as part of institutional programs and the strategic objectives of the hospital. The PROA should include specific objectives based on measurable indicators, and activities aimed at improving the use of antimicrobials, mainly through educational activities and interventions based more on training activities directed to prescribers than just on restrictive measures.

Influenza-like illness in pregnant women during summertime: clinical, epidemiological and microbiological features.

It is not known whether influenza-like illnesses (ILI) in pregnant women caused by influenza virus, specifically, those caused by the 2009 Influenza A H1N1 virus (nH1N1), can be clinically distinguished from those caused by other agents. From 1st July 2009 until 20th September 2009, an observational study including all pregnant women presenting at Hospital Universitario La Paz with an ILI was carried out. A specific reverse-transcriptase polymerase chain reaction (RT-PCR) for nH1N1 in nasopharyngeal swabs was prospectively carried out in all patients. Retrospectively, samples were analysed for multiple respiratory virus panel (RT-PCR microarray). Clinical, demographical and other microbiological variables were evaluated as well. A total of 45 pregnant women with ILI were admitted. Of these, 14 (31.1%) women had nH1N1 infection and 11 with a non-influenza ILI (35.48%) were positive for other viruses (five rhinovirus, four parainfluenza virus, one bocavirus and one adenovirus). In 20 patients, no aetiologic agent was identified. The clinical course of nH1N1 was mild, without deaths or severe complications. No significant differences were found when comparing the clinical presentation and course of patients with and without nH1N1 infection. Six women with nH1N1 infection received oseltamivir. Influenza and non-influenza ILI were clinically indistinguishable among pregnant women. Many ILI in pregnant women remain undiagnosed, despite undergoing an RT-PCR microarray for several respiratory viruses.

Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain.

The risk factors for complications in patients with influenza A (H1N1)v virus infection have not been fully elucidated. We performed an observational analysis of a prospective cohort of hospitalized adults with confirmed pandemic influenza A (H1N1)v virus infection at 13 hospitals in Spain, between June 12 and November 10, 2009, to identify factors associated with severe disease. Severe disease was defined as the composite outcome of intensive-care unit (ICU) admission or in-hospital mortality. During the study period, 585 adult patients (median age 40 years) required hospitalization because of pandemic (H1N1) 2009. At least one comorbid condition was present in 318 (54.4%) patients. Pneumonia was diagnosed in 234 (43.2%) patients and bacterial co-infection in 45 (7.6%). Severe disease occurred in 75 (12.8%) patients, of whom 71 required ICU admission and 13 (2.2%) died. Independent factors for severe disease were age <50 years (OR, 2.39; 95% CI, 1.05-5.47), chronic comorbid conditions (OR, 2.93; 95% CI, 1.41-6.09), morbid obesity (OR, 6.7; 95% CI, 2.25-20.19), concomitant and secondary bacterial co-infection (OR, 2.78; 95% CI, 1.11-7) and early oseltamivir therapy (OR, 0.32; 95% CI 0.16-0.63). In conclusion, although adults hospitalized for pandemic (H1N1) 2009 suffer from significant morbidity, mortality is lower than that reported in the earliest studies. Younger age, chronic comorbid conditions, morbid obesity and bacterial co-infection are independent risk factors for severe disease, whereas early oseltamivir therapy is a protective factor.

Perspectives from Spanish infectious diseases professionals on 2009 A (H1N1) influenza: the third half.

The first influenza pandemic in more than 40 years was declared in 2009. We aimed to evaluate the beliefs of Spanish infectious diseases professionals regarding several aspects of 2009 A (H1N1) influenza once the epidemic waned. An online survey was designed and distributed among members of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). The survey considered hospital organization and preparedness planning and conduct, as well as the opinion of the infectious diseases professionals regarding several key issues. Between 7 March and 22 March 2010, 303 responses, corresponding to 12.8% of the SEIMC membership, were received. Of the respondents, 48.2% were microbiologists and 42.3% were clinicians dealing with infectious diseases. Forty-one per cent of respondents did not believe that 2009 A (H1N1) influenza had a more severe presentation than other seasonal influenzas. Only 5% fully agreed that 2009 A (H1N1) influenza had a more severe presentation. Influenza planning was available in 69.7% of represented institutions before the arrival of 2009 A (H1N1) influenza, and was considered to be useful, to different extents, by most professionals. In most institutions (88.3%), a multidisciplinary team was created to coordinate local pandemic influenza actions. The most successful protocols were those provided by regional healthcare authorities, followed by those from the CDC. The most problematic issues regarding 2009 A (H1N1) influenza were the management of patients in the emergency room and the vaccination and awareness of healthcare professionals (HCPs) regarding infection control. Microbiological diagnosis and the availability of antivirals were the least problematic areas. Although the majority of surveyed infectious diseases professionals did not believe that 2009 A (H1N1) influenza had an especially severe presentation, most of them agreed with the way that this epidemic was managed in their institutions.