Current and future perspectives in the treatment of multidrug-resistant Gram-negative infections.

Microbial resistance is a serious threat to human health worldwide. Among the World Health Organisation's list of priority resistant bacteria, three are listed as critical-the highest level of concern-and all three are Gram-negative. Gram-negative resistance has spread worldwide via a variety of mechanisms, the most problematic being via AmpC enzymes, extended-spectrum ß-lactamases, and carbapenemases. A combination of older drugs, many with high levels of toxicity, and newer agents are being used to combat multidrug resistance, with varying degrees of success. This review discusses the current treatments for multidrug-resistant Gram-negative bacteria, including new agents, older compounds, and new combinations of both, and some new treatment targets that are currently under investigation.

Clinical and economic impact of bacterial resistance: an approach to infection control and antimicrobial stewardship solutions.

PURPOSE OF REVIEW: The aim of this study was to describe the clinical and economic burden of bacterial antimicrobial resistance (AMR) and to provide an expert opinion on different approaches to fight it. RECENT FINDINGS: For several decades now, it has been known that AMR among human pathogens is related to high clinical and economic burden.Different strategies have been implemented to control the clinical and economic burden of AMR. Antimicrobial stewardship programmes (ASP), environmental cleaning and infection source control have been reported as the most effective interventions. There is a potential role for faecal microbiome transplant (FMT); however, long-term effectiveness and safety remain to be demonstrated. Another promising tool is to develop molecules to chelate or degrade residual antibiotics in the colon. Decolonization has demonstrated impact on methicillin-resistant Staphylococcus aureus (MRSA) infections, but there is limited evidence on the clinical impact and effectiveness of decolonization in MDR Gram-negative carriers. SUMMARY: A better assessment of AMR rates and the clinical and economic impact is needed. The epidemiology of AMR bacteria varies in different regions with MRSA, extended-spectrum beta-lactamase and carbapenamase-producing Enterobacterales being the most worrying. ASP and infection control have been increasingly demonstrated to impact on AMR rates. New approaches such as FMT and decolonization have still to demonstrate efficacy and safety.

Microbiological Etiologies of Pneumonia Complicating Stroke: A Systematic Review.

BACKGROUND AND PURPOSE: Identifying the causal pathogens of pneumonia complicating stroke is challenging, and antibiotics used are often broad spectrum, without recourse to the microbiological cause. We aimed to review existing literature to identify organisms responsible for pneumonia complicating stroke, before developing a consensus-based approach to antibiotic treatment. METHODS: A systematic literature review of multiple electronic databases using predefined search criteria was undertaken, in accordance with Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance. Published studies of hospitalized adults with ischemic stroke, intracerebral hemorrhage, or both, which identified microbiological etiologies for pneumonia complicating stroke up to January 1, 2017, were considered. Analysis included summary statistics and random-effects meta-analysis where appropriate. RESULTS: Fifteen studies (40% ischemic stroke, 60% ischemic stroke and intracerebral hemorrhage) involving 7968 patients were included. Reported occurrence of pneumonia varied considerably between studies (2%-63%) with a pooled frequency of 23% (95% confidence interval, 14%-34%; I2=99%). Where reported (60%), the majority of pneumonia occurred within 1 week of stroke (78%). Reported frequency of positive culture data (15%-88%) varied widely. When isolated, aerobic Gram-negative bacilli (38%) and Gram-positive cocci (16%) were most frequently cultured; commonly isolated organisms included Enterobacteriaceae (21.8%: Klebsiella pneumoniae, 12.8% and Escherichia coli, 9%), Staphylococcus aureus (10.1%), Pseudomonas aeruginosa (6%), Acinetobacter baumanii (4.6%), and Streptococcus pneumoniae (3.5%). Sputum was most commonly used to identify pathogens, in isolation (40%) or in conjunction with tracheal aspirate (15%) or blood culture (20%). CONCLUSIONS: Although the analysis was limited by small and heterogeneous study populations, limiting determination of microbiological causality, this review suggests aerobic Gram-negative bacilli and Gram-positive cocci are frequently associated with pneumonia complicating stroke. This supports the need for appropriately designed studies to determine microbial cause and a consensus-based approach in antibiotic usage and further targeted antibiotic treatment trials for enhanced antibiotic stewardship.

Predictive and prognostic factors in patients with blood-culture-positive community-acquired pneumococcal pneumonia.

In patients with pneumococcal community-acquired pneumonia (CAP), the risk factors for bacteraemia and its impact on outcomes are not fully elucidated. We aimed to compare characteristics of patients with blood-culture-positive versus blood-culture-negative pneumococcal CAP, and to characterise bacteraemic serotypes.We describe a prospective, observational study on nonimmunocompromised patients with pneumococcal CAP, from 1996 to 2013. We define severe pneumonia according to American Thoracic Society/Infectious Diseases Society of America guidelines.Of a total of 917 patients with pneumococcal CAP, 362 had blood-culture-positive pneumococcal pneumonia (BCPPP; 39%). High C-reactive protein (CRP) (≥20 mg·dL(-1)) (odds ratio (OR) 2.36, 95% CI 1.45-3.85), pleural effusion (OR 2.03, 95% CI 1.13-3.65) and multilobar involvement (OR 1.69, 95% CI 1.02-2.79) were independently associated with bacteraemic CAP, while nursing home resident (OR 0.12, 95% CI 0.01-1.00) was found as a protective factor. Despite the clinical differences, BCPPP showed similar outcomes to blood-culture-negative pneumococcal pneumonia (BCNPP). 14% of the serotypes (period 2006-2013) causing bacteraemia are included in pneumococcal conjugate vaccine PVC7, 74% in pneumococcal conjugate vaccine PVC13 and 83% in pneumococcal polysaccharide vaccine PPSV23.Pleural effusion, a high level of CRP and multilobar involvement predicted an increased risk of BCPPP. Although BCPPP patients were more severely ill at admission, mortality was not significantly greater than in BCNPP patients.

How is pneumonia diagnosed in clinical stroke research? A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Diagnosis of pneumonia complicating stroke is challenging, and there are currently no consensus diagnostic criteria. As a first step in developing such consensus-based diagnostic criteria, we undertook a systematic review to identify the existing diagnostic approaches to pneumonia in recent clinical stroke research to establish the variation in diagnosis and terminology. METHODS: Studies of ischemic stroke, intracerebral hemorrhage, or both, which reported occurrence of pneumonia from January 2009 to March 2014, were considered and independently screened for inclusion by 2 reviewers after multiple searches using electronic databases. The primary analysis was to identify existing diagnostic approaches for pneumonia. Secondary analyses explored potential reasons for any heterogeneity where standard criteria for pneumonia had been applied. RESULTS: Sixty-four studies (56% ischemic stroke, 6% intracerebral hemorrhage, 38% both) of 639 953 patients were included. Six studies (9%) reported no information on the diagnostic approach, whereas 12 (19%) used unspecified clinician-reported diagnosis or initiation of antibiotics. The majority used objective diagnostic criteria: 20 studies (31%) used respiratory or other published standard criteria; 26 studies (41%) used previously unpublished ad hoc criteria. The overall occurrence of pneumonia was 14.3% (95% confidence interval 13.2%-15.4%; I(2)=98.9%). Occurrence was highest in studies applying standard criteria (19.1%; 95% confidence interval 15.1%-23.4%; I(2)=98.5%). The substantial heterogeneity observed was not explained by stratifying for other potential confounders. CONCLUSIONS: We found considerable variation in terminology and the diagnostic approach to pneumonia. Our review supports the need for consensus development of operational diagnostic criteria for pneumonia complicating stroke.

Diagnosis of Stroke-Associated Pneumonia: Recommendations From the Pneumonia in Stroke Consensus Group.

BACKGROUND AND PURPOSE: Lower respiratory tract infections frequently complicate stroke and adversely affect outcome. There is currently no agreed terminology or gold-standard diagnostic criteria for the spectrum of lower respiratory tract infections complicating stroke, which has implications for clinical practice and research. The aim of this consensus was to propose standardized terminology and operational diagnostic criteria for lower respiratory tract infections complicating acute stroke. METHODS: Systematic literature searches of multiple electronic databases were undertaken. An evidence review and 2 rounds of consensus consultation were completed before a final consensus meeting in September 2014, held in Manchester, United Kingdom. Consensus was defined a priori as ≥75% agreement between the consensus group members. RESULTS: Consensus was reached for the following: (1) stroke-associated pneumonia (SAP) is the recommended terminology for the spectrum of lower respiratory tract infections within the first 7 days after stroke onset; (2) modified Centers for Disease Control and Prevention (CDC) criteria are proposed for SAP as follows-probable SAP: CDC criteria met, but typical chest x-ray changes absent even after repeat or serial chest x-ray; definite SAP: CDC criteria met, including typical chest x-ray changes; (3) there is limited evidence for a diagnostic role of white blood cell count or C-reactive protein in SAP; and (4) there is insufficient evidence for the use of other biomarkers (eg, procalcitonin). CONCLUSIONS: Consensus operational criteria for the terminology and diagnosis of SAP are proposed based on the CDC criteria. These require prospective evaluation in patients with stroke to determine their reliability, validity, impact on clinician behaviors (including antibiotic prescribing), and clinical outcomes.

Epidemiology and risk factors for infections due to AmpC ß-lactamase-producing Escherichia coli.

OBJECTIVES: To describe the prevalence and risk factors for infection due to AmpC ß-lactamase-producing Escherichia coli (AmpC-EC). METHODS: For the prevalence study, all clinical isolates of E. coli with reduced susceptibility to third-generation cephalosporins were prospectively included from June 2010 to November 2011. For risk factor analysis, a case-control study was conducted. Cases were patients with an infection due to AmpC-EC. Controls were patients infected with cephalosporin-susceptible E. coli, matched 1 : 2. Detection of blaAmpC genes was done with a multiplex AmpC-PCR, and hyperproduction of E. coli chromosomal blaAmpC by quantitative RT-PCR. Alteration of the blaAmpC promoter was studied by PCR and sequencing. RESULTS: We identified 243 (1.1%) AmpC-EC strains out of 21 563 clinical isolates. Three cases with strains carrying ESBLs, 18 strains that were considered due to colonization and 8 cases lost to clinical follow-up were excluded. Finally, 214 cases were included in the analysis. Ninety-one cases (42.5%) and 269 (62.8%) controls were strictly community acquired (P < 0.001). Thirty-five (16.3%) cases and 186 controls (43.5%) did not have any identifiable risk factor (P < 0.001). Among cases, 158 (73.8%) were found to harbour an acquired AmpC (73.4% CMY-2). Previous use of fluoroquinolones [OR 2.6 (95% CI 1.12-3.36); P = 0.008] was independently associated with AmpC-EC in the multivariate analysis. CONCLUSIONS: Prevalence of AmpC in E. coli remains low in our area. Plasmid acquisition (CMY type) represents the main mechanism of AmpC production. A high proportion of community-acquired isolates and patients with no identifiable risk factors were found. Previous use of fluoroquinolones was identified as a risk factor.

Early response to antibiotic treatment in European patients hospitalized with complicated skin and soft tissue infections: analysis of the REACH study.

BACKGROUND: The treatment of complicated skin and soft tissue infections (cSSTI) is challenging and many patients do not receive adequate first-line therapy. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe cSSTI or Community-Acquired Pneumonia in the Hospital Setting) was a retrospective observational study of cSSTI patients in real-life settings in European hospitals. In this analysis, we review characteristics and outcomes of patients with an early response (≤72 hours) compared with those without an early response to treatment. We also compare the results according to two differing definitions of early response, one of which (Definition 1) requires resolution of fever within 72 hours, in line with previous US FDA guidelines. METHODS: Patients were adults hospitalized with cSSTIs 2010-2011 and requiring treatment with intravenous antibiotics. Clinical management, clinical outcomes and healthcare resource use were assessed using a descriptive analysis approach. RESULTS: The analysis set included 600 patients, of which 363 showed early response with Definition 1 and 417 with Definition 2. Initial treatment modification was frequent, and highest in patients without early response (48.1% with Definition 1). Patients without early response were more likely to have diabetes than those with early response (31.6% vs. 22.9%, respectively) and to suffer from more severe disease (e.g. skin necrosis: 14.8% and 7.7%, respectively), to be infected with difficult-to-treat microorganisms and to have recurrent infections. Furthermore, patients without early response had a higher rate of adverse clinical outcomes (e.g. septic shock) and higher use of healthcare resources. The results obtained with the two definitions for early response were largely similar. CONCLUSIONS: This study highlights the significance of early evaluation of patients in hospitals, in potentially preventing prolonged use of inappropriate or ineffective antibacterial therapy. TRIAL REGISTRATION: NCT01293435 .

Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study.

BACKGROUND: Key goals in the treatment of CAP include early response to treatment and achievement of clinical stability. The US FDA recommends early response endpoints (72 hours after initiation of treatment) in clinical trials for the treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a retrospective observational study, providing current data on the clinical management and resource burden of CAP in real-life settings in European hospitals. This analysis reviews the characteristics and outcomes of patients showing early positive response to treatment (time to clinical stability [TCS] ≤4 days, as assessed by Halm's criteria) compared with patients with later positive response (TCS >4 days). METHODS: Patients were adults, hospitalized with CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics. RESULTS: Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253 (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's criteria varied across participating countries, ranging from 0% (Belgium) to 49.1% (UK). Patient characteristics and relevant medical history were similar between the two groups. There were no notable differences in initial antibiotic therapy between groups, except that more early responders had been treated with amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively) than later responders (5.9%; 1.2%, respectively). Initial treatment modification and re-infection or recurrences were less frequent in early responders compared with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early responders had a shorter duration of hospitalization (mean 9.4 ± SD 7.0; median 8.0 days vs. mean 15.6 ± SD 10.5; median 12.0 days, respectively), lower rate of ICU admission (3.3% vs. 21.3%) and shorter duration of ICU stay (mean 6.2 ± SD 5.7; median 4.0 days vs. mean 10.4 ± SD 10.1; median 8.0 days, respectively) compared with later responders. Mortality was low in both groups. CONCLUSIONS: Achieving early clinical stabilization in CAP (≤4 days) is associated with improved outcomes, lower requirement for initial treatment modification or readmission and lower resource use, compared with a later response. TRIAL REGISTRATION: NCT01293435.

Resource use by patients hospitalized with community-acquired pneumonia in Europe: analysis of the REACH study.

BACKGROUND: Management of community-acquired pneumonia (CAP) places a considerable burden on hospital resources. REACH was a retrospective, observational study (NCT01293435) involving adults ≥18 years old hospitalized with CAP and requiring in-hospital treatment with intravenous antibiotics conducted to collect data on current clinical management patterns and resource use for CAP in hospitals in ten European countries. METHODS: Data were collected via electronic Case Report Forms detailing patient and disease characteristics, microbiological diagnosis, treatments before and during hospitalization, clinical outcomes and health resource consumption. RESULTS: Patients with initial antibiotic treatment modification (n = 589; 28.9%) had a longer mean hospital stay than those without (16.1 [SD: 13.1; median 12.0] versus 11.1 [SD: 8.9; median: 9.0] days) and higher ICU admission rate (18.0% versus 11.9%). Septic shock (6.8% versus 3.0%), mechanical ventilation (22.2% versus 9.7%), blood pressure support (fluid resuscitation: 19.4% versus 11.4%), parenteral nutrition (6.5% versus 3.9%) and renal replacement therapy (4.2% versus 1.4%) were all more common in patients with treatment modification than in those without. Hospital stay was longer in patients with comorbidities than in those without (mean 13.3 [SD: 11.1; median: 10.0] versus 10.0 [SD: 7.5; median: 8.0] days). CONCLUSIONS: Initial antibiotic treatment modification in patients with CAP is common and is associated with considerable additional resource use. Reassessment of optimal management paradigms for patients hospitalized with CAP may be warranted.

Current management of patients hospitalized with community-acquired pneumonia across Europe: outcomes from REACH.

BACKGROUND: Data describing real-life management and treatment of community-acquired pneumonia (CAP) in Europe are limited. REACH (http://NCT01293435) was a retrospective, observational study collecting data on the management of EU patients hospitalized with CAP. METHODS: Patients were aged ≥18 years, hospitalized with CAP between March 2010 and February 2011, and requiring in-hospital treatment with intravenous antibiotics. An electronic Case Report Form was used to collect patient, disease and treatment variables, including type of CAP, medical history, treatment setting, antibiotics administered and clinical outcomes. RESULTS: Patients (N = 2,039) were recruited from 128 centres in ten EU countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Turkey, UK). The majority of patients were aged ≥65 years (56.4%) and had CAP only (78.8%). Initial antibiotic treatment modification occurred in 28.9% of patients and was more likely in certain groups (patients with comorbidities; more severely ill patients; patients with healthcare-associated pneumonia, immunosuppression or recurrent episodes of CAP). Streamlining (de-escalation) of therapy occurred in 5.1% of patients. Mean length of hospital stay was 12.6 days and overall mortality was 7.2%. CONCLUSION: These data provide a current overview of clinical practice in patients with CAP in EU hospitals, revealing high rates of initial antibiotic treatment modification. The findings may precipitate reassessment of optimal management regimens for hospitalized CAP patients.

Improvement of pneumococcal pneumonia diagnosis using quantitative real-time PCR targeting lytA in adult patients: a prospective cohort study.

OBJECTIVES: The aim of the study was to assess the performance of real-time PCR targeting the lytA gene (rtPCR-lytA) in plasma, urine and nasopharyngeal (NP) samples for the diagnosis of pneumococcal community-acquired pneumonia (P-CAP). METHODS: Prospective observational study including all consecutive adults with CAP from November 2015 to May 2017. P-CAP was defined if pneumococcus was identified using conventional methods (CM) and/or a positive rtPCR-lytA was detected in blood, urine or NP samples (NP cut-off ≥8000 copies/mL). Diagnostic performance of each test was calculated. RESULTS: A total of 133 individuals with CAP were included. Of these, P-CAP was diagnosed in 62 (46.6%). The proportion of P-CAP diagnosed by rtPCR-lytA methods was significantly higher than that diagnosed by CM (87.1% versus 59.7%, p 0.005). The rtPCR-lytA identified Streptococcus pneumoniae in 25 patients (40.3% of all individuals with P-CAP) whose diagnosis would have been missed by CM. NP-rtPCR-lytA allowed diagnosis of 62.3% of P-CAP. A nasopharyngeal colonization density ≥2351 copies/mL predicted P-CAP diagnosis (area under the curve = 0.82, sensitivity 83.3%, specificity 80.9%). There was a positive correlation between increasing bacterial load in blood and CURB-65 score (Spearman correlation coefficient r = 0.4, p 0.001), pneumonia severity index (r = 0.3, p 0.02) and time to clinical stability (r = 0.33, p 0.01). Median bacterial load in blood was higher in P-CAP patients with bacteraemia (0.65 × 103 versus 0 × 103 copies/mL, p 0.002), intensive care unit admission (0.68 × 103 versus 0 × 103 copies/mL, p 0.04) or mechanical ventilation (7.45 × 103 versus 0 × 103 copies/mL, p 0.04). CONCLUSIONS: The use of rtPCR-lytA methods significantly increased the diagnosis of P-CAP compared with CM. Nasopharyngeal swabs rtPCR-lytA detection, with an accurate cut-off value, was the most promising among molecular methods for the diagnosis of P-CAP.

Short versus long course therapy in the treatment of febrile urinary tract infections in men based on serum PSA values.

BACKGROUND: Febrile urinary tract infections (fUTI) in men are frequently complicated with subclinical prostatic involvement, measured by a transient increase in serum prostate-specific-antigen (sPSA). The aim of this study was to evaluate recurrence rates in a 6-month follow-up period of 2-week versus 4-week antibiotic treatment in men with fUTI, based on prostatic involvement. Clinical and microbiological cure rates at the end-of-therapy (EoT) were also assessed. METHODS: Open label, not-controlled, prospective study. Consecutive men diagnosed of fUTI were included. Duration of therapy was 2 weeks for patients with a sPSA level <5mg/L (short duration therapy, SDT) or 4 weeks for PSA >5 mg/L (long duration therapy, LDT). RESULTS: Ninety-one patients were included; 19 (20%) received SDT. Median age was 56.9 years (range 23-88). Bacteremia was present in 9.8% of patients (Escherichia coli was isolated in 91%). Both groups had similar demographic, clinical characteristics and laboratory findings. Median PSA levels were 2.3 mg/L in the SDT group vs 23.4 mg/L in the LDT group. In the 6-month visit, 26% of patients had achieved complete follow-up. Nonsignificant differences between groups were found neither in recurrence rates after 6 months (9% in SDT vs 10% in LDT) nor in clinical or microbiological cure rates at EoT (100% in SDT vs 95% in LDT and 95% in SDT vs 93% in LDT respectively). CONCLUSIONS: One fifth of men with fUTI did not present apparent prostatic involvement. A 2-week regimen seems adequate in terms of clinical, microbiological cure and recurrence rates for those patients without PSA elevation.

Foodborne nosocomial outbreak of SHV1 and CTX-M-15-producing Klebsiella pneumoniae: epidemiology and control.

BACKGROUND: We describe a foodborne nosocomial outbreak due to extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae. METHODS: An outbreak of ESBL K. pneumoniae was detected in March 2008. Initial control measures included contact isolation and a protocol for routine detection and reinforcement in hand hygiene practices. ESBL producers were screened for the bla(TEM), bla(SHV), and bla(CTX-M) genes. Pulsed-field gel electrophoresis analysis was performed using XbaI as a restriction endonuclease. RESULTS: One hundred fifty-six colonized and/or infected patients were identified, 35 (22.4%) of whom had infection. The outbreak affected all hospital wards. Fecal carriage was up to 38% of patients in some wards. Of note, investigation revealed a very short delay between admission and colonization. None of the health care workers or environmental surfaces in the wards was found to be colonized. This prompted an epidemiological investigation of a possible foodborne transmission. We found that up to 35% of the hospital kitchen-screened surfaces or foodstuff were colonized and that 6 (14%) of 44 food handlers were found to be fecal carriers. Phenotypic and genotypic analysis of all clinical, environmental, and fecal carrier isolates showed the dissemination of a single strain of SHV-1 and CTX-M-15-producing K. pneumoniae. At that time, structural and functional reforms in the kitchen were performed. These were followed by a progressive reduction in colonization and infection rates among inpatients until complete control was obtained in December 2008. No restrictions in the use of antibiotics were needed. CONCLUSIONS: To our knowledge, this is the first reported hospital outbreak that provides evidence that food can be a transmission vector for ESBL K. pneumoniae.

Factors affecting the development of systemic inflammatory response syndrome in pneumococcal infections.

PURPOSE OF REVIEW: Streptococcus pneumoniae continues to be responsible for significant mortality and morbidity worldwide. A better understanding of the inflammatory response generated by the interaction of this microorganism with the host and antimicrobial therapy will improve the management of patients with pneumococcal infection. RECENT FINDINGS: On the side of the microorganism, recent studies have identified virulence factors such as capsular polysaccharides, surface protein, pili and pneumolysin, among others, that are able to trigger a complex inflammatory network. A misbalance in this network will precipitate a specific response that generates the systemic inflammatory response syndrome. Some of these virulence factors could be used as antigens for the production of vaccines with a broader spectrum than the currently used ones. On the host side, many single-nucleotide polymorphisms in genes controlling the immune response have been associated with specific clinical presentations. Finally, some antimicrobials or adjunctive therapies have recently been evaluated as inmunomodulatory agents. SUMMARY: Systemic inflammatory response syndrome is the result of an anomalous activation of the inflammatory network triggered by S. pneumoniae. Pneumococcal virulence factors, host comorbidities, the genetic background and the concomitant activity of antimicrobials and adjuvant therapies modulate the magnitude of this response.

New trends in infective endocarditis.

The present article is an update of the literature on endocarditis. A multidisciplinary group of Spanish physicians with an interest in cardiac infections selected the most important papers produced lately in the field. Two of the members of the group discussed the content of each of the selected papers, with a critical review by others members of the panel. After a review of the state of the art papers from the fields of epidemiology, new causative microorganisms (bacterial and fungal), clinical findings including those in special patients, laboratory diagnosis, prognostic factors, nosocomial endocarditis, prophylaxis, new drugs and guidelines for antibiotic treatment were discussed by the group.

Related Factors to Streptococcus pneumoniae Invasive Infection and Clinical Manifestations: The Potential Role of Nasopharyngeal Microbiome.

Infections of the lower respiratory tract, such as pneumonia, are one of the leading causes of death worldwide. Streptococcus pneumoniae might colonize the upper respiratory tract and is the main aetiological agent of community-acquired pneumonia (CAP). In the last decades, several factors related to the host, the microorganism and the antibiotic therapy have been investigated to identify risk factors associated with the development of invasive pneumococcal disease (IPD). Nevertheless, these factors themselves do not explain the risk of developing disease or its severity. Recently, some studies have focused on the importance of nasopharyngeal (NP) microbiome and its relation to respiratory health. This review presents existing evidence of the potential role of NP microbiome in the development of IPD.

[Relationships with microbiology: the view from other specialties]. / Las relaciones con la microbiología: la visión desde otras especialidades.

The major advances produced in infectious diseases, partly favored by technological development in the last few years, together with current changes in healthcare, have led to a new scenario in which, far from the control of infectious diseases, clinical microbiology has acquired an undoubted leading role. This new panorama implies collaboration among distinct health professionals within the same healthcare setting, with common and occasionally conflicting interests. Setting aside the individual differences that can be produced in the daily life of our hospitals, all health professionals should understand one another, not only because such cooperation is required for optimal patient care but also because synergistic collaboration among professions would improve professional development. Based on this principle of a multidisciplinary approach, collaboration and mutual respect, the moment seems opportune for the various professionals involved in infectious diseases (infectologists, internists, pediatricians and intensivists) to express their view of the specialty of clinical microbiology. The present article includes reflections, from a highly liberal and personal point of view, on how mutual relationships can be approached and on how greater knowledge of infectious diseases can continue to be gained in Spain. In all these reflections, the questions of where we come from and where we are going are explicit or implicit.

Update on the role of ceftazidime-avibactam in the management of carbapenemase-producing Enterobacterales.

Ceftazidime-avibactam is a novel combination of a known cephalosporin and a non-ß-lactam/ß-lactamase inhibitor that has been approved for the treatment of complicated intra-abdominal and urinary tract infections, hospital-acquired pneumonia as well as Gram-negative infections with limited treatment options in Europe. Since its approval, it has been used in patients with infections due to carbapenem-resistant bacteria, in many occasions as off-label indication or salvage therapy, with promising clinical and microbiological cure rates. Emergence of resistance during therapy to this new combination has already been described, which is a matter of concern. A rational use of these new therapeutic options is critical in the multidrug resistance era. The current review focuses on the clinical experience in real life of ceftazidime-avibactam use in the treatment of carbapenemase-producing Enterobacterales.