Strongyloidiasis is an intestinal parasitic infection becoming increasingly important outside endemic areas, not only because of the high prevalence found in migrant populations, but also because ...immunosuppressed patients may suffer a potentially fatal disseminated disease. The aim of these guidelines is to provide evidence-based guidance for screening and treatment of strongyloidiasis in non-endemic areas. A panel of experts focused on three main clinical questions (who should be screened and how, how to treat), and reviewed pertinent literature available in international databases of medical literature and in documents released by relevant organizations/societies. A consensus of the experts' opinion was sought when specific issues were not covered by evidence. In particular, six systematic reviews were retrieved and constituted the main support for this work. The evidence and consensus gathered led to recommendations addressing various aspects of the main questions. Grading of evidence and strength of recommendation were attributed to assess the quality of supporting evidence. The screening of individuals at risk of the infection should be performed before they develop any clinical complication. Moreover, in immunosuppressed patients, the screening should be mandatory. The screening is based on a simple and widely accessible technology and there is now a universally accepted treatment with a high efficacy rate. Therefore, the screening could be implemented as part of a screening program for migrants although further cost-effectiveness studies are required to better evaluate this strategy from a public health point of view.
•Alternative therapies were tested in a PK/PD biofilm model by multidrug-resistant/extensively drug-resistant (MDR/XDR) Pseudomonas aeruginosa•Ceftolozane/tazobactam alone had little anti-biofilm ...efficacy•Colistin alone had notable efficacy, but it was influenced by resistance•Ceftolozane/tazobactam-colistin was the best therapy for meropenem-resistant strains•Meropenem-colistin was the most effective combination for MDR/XDR susceptible strains
Ceftolozane/tazobactam is a potential tool for infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa), but its efficacy against some difficult-to-treat infections has not been well defined.
Using an in vitro pharmacodynamic biofilm model, this study evaluated the comparative efficacy of ceftolozane/tazobactam against MDR/extensively drug-resistant (XDR) P. aeruginosa strains, alone and in combination with colistin. Simulated regimens of ceftolozane/tazobactam (2 g/1 g every 8 h), meropenem (2 g every 8 h) and ceftazidime (2 g every 8 h), alone and in combination with colistin (continuous infusion) were evaluated against three colistin-susceptible and ceftazidime-resistant strains: MDR-HUB1, ceftolozane/tazobactam-susceptible and meropenem-susceptible; XDR-HUB2, ceftolozane/tazobactam-susceptible and meropenem-resistant; MDR-HUB3, ceftolozane/tazobactam-resistant and meropenem-susceptible. Antibiotic efficacy was evaluated by decreases in bacterial counts (Δlog CFU/mL) from biofilm-embedded bacteria over 54 h. Resistance emergence was screened.
Among monotherapies, ceftolozane/tazobactam had low killing but no resistance appeared, ceftazidime was ineffective, colistin was initially effective but regrowth and resistance occurred, and meropenem was bactericidal against carbapenem-susceptible strains. Ceftolozane/tazobactam plus colistin was the most effective combination against the meropenem-resistant XDR-HUB2 strain (Δlog CFU/mL 54–0 h = –4.42 vs. –3.54 for meropenem-colistin; P = 0.002), whereas this combination against MDR-HUB1 (–4.36) was less effective than meropenem-colistin (–6.25; P < 0.001). Ceftolozane/tazobactam plus colistin was ineffective against the ceftolozane/tazobactam-resistant strain; meropenem plus colistin was the most bactericidal therapy (–6.37; P < 0.001 vs. others). Combinations of active beta-lactams plus colistin prevented the emergence of colistin-resistant strains.
Combinations of colistin plus ceftolozane/tazobactam and meropenem were the most appropriate treatments for biofilm-related infections caused by XDR and MDR P. aeruginosa strains, respectively. These combinations could be considered as potential treatment options for these difficult to treat infections.
The objective of this study was to assess the incidence of infection in patients with cutout after proximal femur fracture (PFF) osteosynthesis.
Retrospective cohort study.
Third-level trauma center.
...Patients presenting with a cutout following PFF (OTA/AO 31A) osteosynthesis, between January 2007 and December 2020.
The primary outcome was infection according to the European Bone and Joint Infection Society criteria.
Sixty-seven patients presenting with a cutout were included, with mean age of 83.3 years (range 63-96), and 51 (76.1%) were women. Of all cases, 16 (24.7%) presented a concomitant infection. The presence of concomitant infection was suspected preoperatively in only 3 of the cases. A subgroup analysis was performed between the cases with infection and those without infection, the groups being comparable in terms of demographic data and postoperative radiological criteria. Patients with underlying infection had a higher rate of surgical wound complication (56.3% vs. 22%, P = 0.014) and higher rates of leukocytosis (11.560 vs. 7.890, P = 0.023).
Faced with a cutout after osteosynthesis of a PFF, underlying infection should be considered as a possible etiological factor.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Purpose
The primary aim of the present study is to report the late acute hematogenous (LAH) prosthetic joint infection (PJI) cure rate following Total knee arthroplasty (TKA) treated by means of ...debridement, antibiotics, and implant retention (DAIR) in a long-term follow-up. The secondary purpose is to report the functional outcomes at that follow-up and to compare them with a non-infected group.
Material and Methods
This study cohort consists of 2,498 TKA performed from September 2005 to April 2010 that had a minimum follow-up of 10 years. The diagnosis of PJI and classification into LAH was done in accordance with the Zimmerli criteria. The primary outcome was the failure rate, defined as death before the end of antibiotic treatment, a further surgical intervention for treatment of infection, life-long antibiotic suppressive treatment or chronic infection. The Knee Society Score (KSS) was used to evaluate clinical outcomes.
Results
Ten patients were diagnosed with acute hematogenous PJI during the study period (0.4%). All of them were managed with DAIR, which was performed by a knee surgeon and/or PJI surgeon. The failure rate was 0% at the 8.5-year (SD, 2.4) follow-up mark. The KSS score was 82.1 vs. 84.1 (p n.s.) at final follow-up.
Conclusion
Although the literature suggests that TKA DAIR for LAH periprosthetic joint infection is associated with high rates of failure, the results presented here suggest a high cure rate with good functional outcomes.
Level of evidence
Level II, prospective cohort study.
Strongyloides stercoralis is a worldwide disseminated parasitic disease that can be transmitted from solid organ transplant (SOT) donors to recipients. We determined the serological prevalence of S. ...stercoralis among deceased individuals from endemic areas considered for SOT donation, using our institution's serum bank.
Retrospective study including all deceased potential donors from endemic areas of strongyloidiasis considered for SOT between January 2004 and December 2014 in a tertiary care hospital. The commercial serological test IVD-Elisa was used to determine the serological prevalence of S. stercoralis.
Among 1025 deceased individuals during the study period, 90 were from endemic areas of strongyloidiasis. There were available serum samples for 65 patients and 6 of them tested positive for S. stercoralis (9.23%). Only one of the deceased candidates was finally a donor, without transmitting the infection.
Among deceased individuals from endemic areas considered for SOT donation, seroprevalence of strongyloidiasis was high. This highlights the importance of adhering to current recommendations on screening for S. stercoralis among potential SOT donors at high risk of the infection, together with the need of developing a rapid diagnostic test to fully implement these screening strategies.
Tools for the evaluation of COVID-19 severity would help clinicians with triage decisions, especially the decision whether to admit to ICU. The aim of this study was to evaluate SeptiCyte RAPID, a ...host immune response assay (Immunexpress, Seattle USA) as a triaging tool for COVID-19 patients requiring hospitalization and potentially ICU care. SeptiCyte RAPID employs a host gene expression signature consisting of the ratio of expression levels of two immune related mRNAs, PLA2G7 and PLAC8, measured from whole blood samples. Blood samples from 146 adult SARS-CoV-2 (+) patients were collected within 48 h of hospital admission in PAXgene blood RNA tubes at Hospital del Mar, Barcelona, Spain, between July 28th and December 1st, 2020. Data on demographics, vital signs, clinical chemistry parameters, radiology, interventions, and SeptiCyte RAPID were collected and analyzed with bioinformatics methods. The performance of SeptiCyte RAPID for COVID-19 severity assessment and ICU admission was evaluated, relative to the comparator of retrospective clinical assessment by the Hospital del Mar clinical care team. In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity: critical vs. mild (AUC = 0.93, p < 0.0001), critical vs. moderate (AUC = 0.77, p = 0.002), severe vs. mild (AUC = 0.85, p = 0.0003), severe vs. moderate (AUC = 0.63, p = 0.05). This discrimination was significantly better (by AUC or p-value) than could be achieved by CRP, lactate, creatine, IL-6, or D-dimer. Some of the critical or severe cases had "early" blood draws (before ICU admission; n = 33). For these cases, when compared to moderate and mild cases not in ICU (n = 37), SeptiCyte RAPID had AUC = 0.78 (p = 0.00012). In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity as defined by the WHO COVID-19 Clinical Management Living Guidance of January 25th, 2021. Measurements taken early (before a patient is considered for ICU admission) suggest that high SeptiScores could aid in predicting the need for later ICU admission.
•Linezolid + rifampicin (RIF) was the best therapy for prosthetic joint infection by levofloxacin-resistant S. aureus.•Trimethoprim/sulfamethoxazole (SXT) + RIF did not prevent the emergence of ...RIF-resistant strains.•Concerns for clinical use of SXT + RIF should be further investigated.
Combinations of linezolid (LZD) or trimethoprim/sulfamethoxazole (SXT) plus rifampicin (RIF) are alternative oral treatments for staphylococcal prosthetic joint infections (PJIs) when fluoroquinolones are not possible to use, but there is limited evidence regarding their activity. This study evaluated the efficacy of LZD and SXT, alone and in combination with RIF, against Staphylococcus aureus in an in vitro pharmacokinetic/pharmacodynamic biofilm model. Using the CDC Biofilm Reactor® system, simulated regimens of LZD (600 mg every 12 h), SXT (160/800 mg every 8 h) and levofloxacin (LVX) (750 mg/day), alone and in combination with RIF (600 mg/day), were evaluated against one methicillin-susceptible S. aureus (MSSA) and one methicillin-resistant S. aureus (MRSA) strain. Antibiotic efficacy was evaluated by the decrease in planktonic bacterial counts from medium and biofilm-embedded bacteria from coupons over 56 h. Resistant strains were screened. In both strains, SXT alone was ineffective and LZD presented low activity, but no resistance emerged. Combinations with RIF significantly increased the antibiofilm efficacy against MSSA (Δlog CFU/mL 56h–0h: SXT + RIF, −2.9 and LZD + RIF, −3.1), but RIF-resistant strains appeared with SXT + RIF. Against MRSA, LZD + RIF (−3.1) protected against the emergence of resistance and was more effective than SXT + RIF (−0.6; P < 0.05), in which RIF-resistant strains were again detected. LVX + RIF confirmed its high efficacy against biofilm-embedded bacteria, this being the most effective therapy (−5.1 against MSSA). The emergence of RIF-resistant strains with SXT + RIF poses serious concerns for its use in clinical practice. Interestingly, LZD + RIF appears to be an appropriate alternative for PJI caused by LVX-resistant S. aureus.
Community-acquired pneumonia (CAP) is a frequent complication of chronic obstructive pulmonary disease (COPD), but previous studies are often contradictory.
We aimed to ascertain the characteristics ...and outcomes of CAP in patients with COPD as well as to determine the risk factors for mortality and Pseudomonas aeruginosa pneumonia in COPD patients with CAP. We also describe the etiology and outcomes of CAP in COPD patients receiving chronic oxygen therapy at home and those receiving inhaled steroids.
An observational analysis of a prospective cohort of hospitalized adults with CAP (1995-2011) was performed.
We documented 4121 CAP episodes, of which 983 (23.9%) occurred in patients with COPD; the median FEV1 value was 50%, and 57.8% were classified as stage III or IV in the GOLD classification. Fifty-eight per cent of patients were receiving inhaled steroids, and 14.6% chronic oxygen therapy at home. Patients with COPD presented specific clinical features. S. pneumoniae was the leading causative organism overall, but P. aeruginosa was more frequent in COPD (3.4 vs. 0.5%; p<0.001). Independent risk factors for case-fatality rate in patients with COPD were multilobar pneumonia, P. aeruginosa pneumonia, and high-risk PSI classes. Prior pneumococcal vaccination was found to be protective. FEV1 was an independent risk factor for P. aeruginosa pneumonia.
CAP in patients with COPD presents specific characteristics and risk factors for mortality. Prior pneumococcal vaccine has a beneficial effect on outcomes. P. aeruginosa pneumonia is associated with low FEV1 values and poor prognosis.
Background. Little is known regarding the optimal treatment of ventriculoperitoneal (VP) shunt infections in adults. Our aim was to assess the efficacy of treatment strategies and to identify factors ...that predict failure. Methods. Retrospective, observational study of patients aged ≥ 12 years with VP shunt infections (1980 -2014). Therapeutic approaches were classified under 4 headings: only antibiotics (OA), one-stage shunt replacement (OSSR), two-stage shunt replacement (TSSR), and shunt removal without replacement (SR). The primary endpoint was failure of the treatment strategy, defined as the absence of definite cerebrospinal fluid (CSF) sterilization or related mortality. The parameters that predicted failure were analyzed using logistic regression. Results. Of 108 episodes (51% male, median age 50 years), 86 were analyzed. Intravenous antibiotics were administered for a median of 19 days. Eighty episodes were treated using strategies that combined antibiotic and surgical treatment (37 TSSR, 24 SR, 19 OSSR) and 6 with OA. Failure occurred in 30% of episodes, mostly due to lack of CSF sterilization in OSSR and OA groups. Twelve percent died of related causes and 10% presented superinfection of the CSF temporary drainage/externalized peritoneal catheter. TSSR was the most effective strategy when VP shunt replacement was attempted. The only independent risk factor that predicted failure was retention of the VP shunt, regardless of the strategy. Conclusions. This is the largest series of VP shunt infections in adults reported to date. VP shunt removal, particularly TSSR when the patient is shunt dependent, remains the optimal choice of treatment and does not increase morbidity.
•Ceftazidime monotherapy and ceftazidime in combination with colistin were tested in a Pseudomonas aeruginosa biofilm model•Continuous infusion (CI; T>MIC=100%) ceftazidime demonstrated ...concentration-dependent killing•Colistin plus 40 mg/L CI ceftazidime had the greatest activity among combinations•Combination therapies avoided the emergence of resistance to colistin/ceftazidime compared with monotherapies•These results support the use of high-dosage CI ceftazidime with colistin against Pseudomonas aeruginosa biofilms
Objectives: The pharmacokinetics/pharmacodynamics of continuous infusion (CI) beta-lactams for Pseudomonas aeruginosa biofilm infections has not been defined. This study evaluated the efficacy of several dosage regimens of CI ceftazidime, with or without colistin, an antibiotic with a potential antibiofilm effect, against biofilm-embedded P. aeruginosa.
Methods: Mature biofilms of the reference strain PAO1 and the clinical isolate HUB8 (both ceftazidime- and colistin-susceptible) were investigated over 54h using a dynamic CDC biofilm reactor. CI dosage regimens were ceftazidime monotherapy (4, 10, 20 and 40 mg/L), colistin monotherapy (3.50 mg/L), and combinations of colistin and ceftazidime (4 or 40 mg/L). Efficacy was evaluated by changes in log10colony-forming units (cfu)/mL and confocal microscopy.
Results: At 54 h, the antibiofilm activity of ceftazidime monotherapies was slightly higher for ceftazidime 20 mg/L (-2.84 log10cfu/mL) and 40 mg/L (-3.05) against PAO1, but no differences were seen against HUB8. Ceftazidime-resistant colonies emerged with 4 mg/L regimens in both strains and with other regimens in PAO1. Colistin monotherapy had significant antibiofilm activity against HUB8 (-3.07), but lower activity against PAO1 (-1.12), and colistin-resistant strains emerged. Combinations of ceftazidime and colistin had higher antibiofilm activity at 54 h compared with each monotherapy, and prevented the emergence of resistance to both antibiotics; higher antibiofilm activity was observed with ceftazidime 40 mg/L plus colistin compared with ceftazidime 4 mg/L plus colistin (-4.19 vs. -3.10 PAO1; -4.71 vs. -3.44 HUB8).
Conclusions: This study demonstrated that, with %T>MIC=100%, CI ceftazidime displayed concentration-dependent antibiofilm activity against P. aeruginosa biofilm, particularly in combination with colistin. These results support the use of high-dosage regimens of CI ceftazidime with colistin against biofilm-associated infections with ceftazidime-susceptible P. aeruginosa.
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