Bacteria are the leading cause of infections after solid organ transplantation. In recent years, a progressive growth in the incidence of multidrug-resistant (MDR) and extensively-drug-reistant (XDR) ...strains has been observed. While methicillin-resistant Staphylococcus aureus (MRSA) infection is declining in non-transplant and SOT patients worldwide, vancomycin-resistant enterococci, MDR/XDR Enterobacteriaceae and MDR/XDR non-fermenters are progressively growing as a cause of infection in solid organ transplant (SOT) patients and represent a global threat. Some SOT patients develop recurrent infections, related to anatomical defects in many cases, which are difficult to treat and predispose patients to the acquisition of MDR pathogens. As the antibiotics active against MDR bacteria have several limitations for their use, which include less clinical experience, higher incidence of adverse effects and less knowledge of the pharmacokinetics of the drug, and, in most cases, are only available for parenteral administration, it is mandatory to know the main characteristics of these drugs to safely treat SOT patients with MDR bacterial infections. Nonetheless, preventive measures are the cornerstone of controlling the spread of these pathogens. Thus, applying the Center for Disease Control and Prevention’s and the European Society of Clinical Microbiology and Infectious Diseases’s recommended antibiotic policies and strategies to control the transmission of MDR strains in the hospital setting is essential for the management of SOT patients.
Recent changes in the management of patients with haematological malignancies might have influenced the aetiology, characteristics, antimicrobial resistance and outcomes of bloodstream infection ...(BSI) during neutropenia. We compared 272 episodes of BSI in adult neutropenic patients with cancer prospectively collected from January 1991 to December 1996 (first period), when quinolone prophylaxis was used, with 283 episodes recorded from January 2006 to March 2010 (second period), when antibacterial prophylaxis was stopped. Patients in the second period were significantly older and were more likely to have graft-versus-host disease and a urinary catheter in place, whereas the presence of a central venous catheter, parenteral nutrition, corticosteroids and antifungal and quinolone prophylaxis, were more frequent in the first period. More patients in the first period had mucositis and soft-tissue infection as the origin of BSI, but an endogenous source was more common during the second. Gram-positive BSI was more frequent in the first period (64% versus 41%; p <0.001), mainly due to coagulase-negative staphylococci and viridans group streptococci. In the second period gram-negative BSI increased (28% versus 49%; p <0.001), quinolone susceptibilities were recovered, but multidrug-resistant gram-negative BSI also increased (1% versus 6%; p <0.001). Although patients in the second period were more likely to need admission to the intensive-care unit, overall case-fatality rate was similar in the two periods (19% versus 15%). The aetiology of BSI in neutropenic patients with cancer has shifted from gram-positive to gram-negative organisms. Multidrug resistance among gram-negative bacilli is emerging as a therapeutic challenge. Overall case-fatality rate remains high.
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are serious complications in transplant patients. The aim of this review is to summarize the evidence regarding nosocomial ...pneumonia in transplant recipients, including HAP in non-ventilated patients and VAP, and to identify future directions for improvement.A comprehensive literature search in the PubMed/MEDLINE database was performed. Articles written in English and published between 1990 and November 2018 were included.
HAP/VAP in transplant patients usually occurs early post-transplant, particularly during neutropenia in haematopoietic stem cell transplant recipients. Bacteria are the leading cause of nosocomial pneumonia for both immunocompetent and transplant recipients, being Gram negative organisms, and especially Pseudomonas aeruginosa, highly prevalent. Multidrug-resistant bacteria are of special concern. Pneumonia in the transplant setting may be caused by opportunistic pathogens, and the differential diagnosis needs to be extended to other non-infectious complications. The most relevant opportunistic pathogens are Aspergillus fumigatus, Pneumocystis jirovecii and cytomegalovirus. Nevertheless, they are an exceptional cause of nosocomial pneumonia, and usually occur in severely immunosuppressed patients not receiving antimicrobial prophylaxis. Performing bronchoalveolar lavage may improve the rate of aetiological diagnosis, leading to a change in therapeutic management and improved outcomes. The optimal length of antibiotic therapy for bacterial HAP/VAP has not been well defined, but it should perhaps be longer than in the general population. Mortality associated with HAP/VAP is high.
HAP/VAP in transplant patients is frequent and is associated with increased mortality. There is room for improvement in gaining knowledge about the management of HAP/VAP in this population.
Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen ...remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-D-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.
Contaminated handwashing sinks have been identified as reservoirs that can facilitate colonization/infection of patients with multidrug-resistant (MDR) Gram-negative bacteria (GNB) in intensive care ...units (ICUs).
To assess the impact of removing patients' sinks and implementing other water-safe strategies on the annual rates of ICU-acquired MDR-GNB.
This six-year quasi-experimental study was conducted from January 2011 to December 2016. The intervention was carried out in August 2014 in two adult ICU wards with 12 rooms each. To assess the changes in annual MDR-GNB rates before and after the intervention, we used segmented regression analysis of an interrupted time-series. Crude relative risk (RR) rates were also calculated.
The incidence rates of MDR-GNB were 9.15 and 2.20 per 1000 patient-days in the pre- and post-intervention periods, respectively. This yielded a crude RR of acquiring MDR-GNB of 0.24 (95% confidence interval: 0.17–0.34). A significant change in level was observed between the MDR-GNB rate at the first point of the post-intervention period and the rate predicted by the pre-intervention time trend.
The implementation of a new water-safe policy, which included the removal of sinks from all patient rooms, successfully improved the control of MDR-GNB spread in an ICU with endemic infection. Our results support the contribution of sink use with the incidence of MDR-GNB in endemic environments.
Concerns have arisen regarding the equivalence of levofloxacin and some macrolides for treating community-acquired legionella pneumonia (LP). We aimed to compare the outcomes of current patients with ...LP treated with levofloxacin, azithromycin and clarithromycin.
Observational retrospective multicentre study of consecutive patients with LP requiring hospitalization (2000–2014) conducted in two hospitals. The primary outcome assessed was 30-day mortality. To control for confounding, therapy was assessed by multivariate analysis.
We documented 446 patients with LP, of which 175 were treated with levofloxacin, 177 with azithromycin and 58 with clarithromycin. No significant differences in time to defervescence (2 (interquartile range (IQR) 1–4) versus 2 (IQR 1–3) days; p 0.453), time to achieve clinical stability (3 (2–5) versus 3 (2–5) days; p 0.486), length of intravenous therapy (3 (2–5.25) versus 4 (3–6) days; p 0.058) and length of hospital stay (7 (5–10) versus 6 (5–9) days; p 0.088) were found between patients treated with levofloxacin and those treated with azithromycin. Patients treated with clarithromycin had longer intravenous antibiotic treatment (3 (2–5.25) versus 5 (3–6.25) days; p 0.002) and longer hospital stay (7 (5–10) versus 9 (7–14) days; p 0.043) compared with those treated with levofloxacin. The overall mortality was 4.3% (19 patients). Neither univariate nor multivariate analysis showed a significant association of levofloxacin versus azithromycin on mortality (4 (2.3%) versus 9 (5.1%) deaths; p 0.164). The results did not change after incorporation of the propensity score into the models.
In our study, no significant differences in most outcomes were found between patients treated with levofloxacin and those treated with azithromycin. Due to the small number of deaths, results regarding mortality should be interpreted with caution.
The optimisation of the use of β-lactam antibiotics (BLA) via prolonged infusions in life-threatening complications such as febrile neutropenia (FN) is still controversial. This systematic review and ...meta-analysis aim to evaluate the efficacy of this strategy in onco-haematological patients with FN.
A systematic search was performed of PubMed, Web of Science, Cochrane, EMBASE, World Health Organization, and ClinicalTrials.gov, from database inception until December 2022. The search included randomised controlled trials (RCTs) and observational studies that compared prolonged vs short-term infusions of the same BLA. The primary outcome was all-cause mortality. Secondary outcomes were defervescence, requirement of vasoactive drugs, length of hospital stay and adverse events. Pooled risk ratios were calculated using random effects models.
Five studies were included, comprising 691 episodes of FN, mainly in haematological patients. Prolonged infusion was not associated with a reduction in all-cause mortality (pRR 0.83; 95% confidence interval 0.47–1.48). Nor differences were found in secondary outcomes.
The limited data available did not show significant differences in terms of all-cause mortality or significant secondary outcomes in patients with FN receiving BLA in prolonged vs. short-term infusion. High-quality RCTs are needed to determine whether there are subgroups of FN patients who would benefit from prolonged BLA infusion.
Healthcare-associated infections caused by Pseudomonas aeruginosa are associated with poor outcomes. However, the role of P. aeruginosa in surgical site infections after colorectal surgery has not ...been evaluated. The aim of this study was to determine the predictive factors and outcomes of surgical site infections caused by P. aeruginosa after colorectal surgery, with special emphasis on the role of preoperative oral antibiotic prophylaxis.
We conducted an observational, multicenter, prospective cohort study of all patients undergoing elective colorectal surgery at 10 Spanish hospitals (2011-2014). A logistic regression model was used to identify predictive factors for P. aeruginosa surgical site infections.
Out of 3701 patients, 669 (18.1%) developed surgical site infections, and 62 (9.3%) of these were due to P. aeruginosa. The following factors were found to differentiate between P. aeruginosa surgical site infections and those caused by other microorganisms: American Society of Anesthesiologists' score III-IV (67.7% vs 45.5%, p = 0.001, odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.44-4.39), National Nosocomial Infections Surveillance risk index 1-2 (74.2% vs 44.2%, p < 0.001, OR 3.6, 95% CI 2.01-6.56), duration of surgery ≥75thpercentile (61.3% vs 41.4%, p = 0.003, OR 2.2, 95% CI 1.31-3.83) and oral antibiotic prophylaxis (17.7% vs 33.6%, p = 0.01, OR 0.4, 95% CI 0.21-0.83). Patients with P. aeruginosa surgical site infections were administered antibiotic treatment for a longer duration (median 17 days interquartile range (IQR) 10-24 vs 13d IQR 8-20, p = 0.015, OR 1.1, 95% CI 1.00-1.12), had a higher treatment failure rate (30.6% vs 20.8%, p = 0.07, OR 1.7, 95% CI 0.96-2.99), and longer hospitalization (median 22 days IQR 15-42 vs 19d IQR 12-28, p = 0.02, OR 1.1, 95% CI 1.00-1.17) than those with surgical site infections due to other microorganisms. Independent predictive factors associated with P. aeruginosa surgical site infections were the National Nosocomial Infections Surveillance risk index 1-2 (OR 2.3, 95% CI 1.03-5.40) and the use of oral antibiotic prophylaxis (OR 0.4, 95% CI 0.23-0.90).
We observed that surgical site infections due to P. aeruginosa are associated with a higher National Nosocomial Infections Surveillance risk index, poor outcomes, and lack of preoperative oral antibiotic prophylaxis. These findings can aid in establishing specific preventive measures and appropriate empirical antibiotic treatment.
Little information is available on the changes over time in community-acquired pneumonia (CAP) management and their impact on 30-day mortality in hospitalized patients. We performed a prospective, ...observational study of non-severely immunosuppressed hospitalized adults with CAP from 1995 to 2014. A total of 4558 patients were included. Thirty-day mortality decreased from 9.6% in the first study period (1995–99) to 4.1% in the last period (2010–14); with a progressive downward trend (–0.2% death/year; p for trend = 0.003). Over time, patients were older (p 0.02), had more co-morbidities (p 0.037), more frequently presented severe illness according to the Pneumonia Severity Index (p <0.001) and septic shock (p <0.001), and more often required intensive care unit admission (p <0.001). Combination antibiotic therapy (p <0.001) and fluoroquinolone use (p <0.001) increased. Factors independently associated with 30-day mortality were increasing age (OR 1.04; 95% CI 1.03–1.05), co-morbidities (OR 1.48; 95% CI 1.04–2.11), shock at admission (OR 4.95; 95% CI 3.49–7.00), respiratory failure (OR 1.89; 95% CI 1.42–2.52), bacteraemia (OR 2.16; 95% CI 1.58–2.96), Gram-negative bacilli aetiology (OR 4.79; 95% CI 2.52–9.10) and fluoroquinolone use (OR 0.45; 95% CI 0.29–0.71). When we adjusted for a propensity score to receive fluoroquinolones, the protective effect of fluoroquinolone use was not confirmed. In conclusion, 30-day mortality decreased significantly over time in hospitalized patients with CAP in spite of an upward trend in patient age and other factors associated with poor outcomes. Several changes in the management of CAP and a general improvement in global care over time may have caused the observed outcomes.
The field of new biological agents is increasing exponentially over the past years, thus making prevention and management of associated infectious complications a challenge for nonspecialized ...clinicians.
The present consensus document is an initiative of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) aimed at analysing, from an infectious diseases perspective, the safety of targeted and biological therapies.
Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family.
The document is structured in sections according to the targeted site of action of each drug class: proinflammatory cytokines; interleukins, immunoglobulins and other soluble immune mediators; cell surface receptors and associated signaling pathways; intracellular signaling pathways; lymphoma and leukaemia cells surface antigens; and other targeted therapies. A common outline is followed for each agent: summary of mechanism of action, approved indications and common off-label uses; expected impact on the host's susceptibility to infection; available clinical evidence (i.e. pivotal clinical trials, postmarketing studies, case series and case reports); and suggested prevention and risk minimization strategies. The methodologic and practical difficulties of assessing the specific risk posed by a given agent are also discussed.
This ESGICH consensus document constitutes not only a comprehensive overview of the molecular rationale and clinical experience on the risk of infection associated with approved targeted therapies but also an attempt to propose a series of recommendations with the purpose of guiding physicians from different disciplines into this emerging framework.
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