Adequate Antimicrobial Treatment Research Articles

Characteristics and Outcome of Vascular Graft Infections - A Risk Factor and Survival Analysis

Abstract Background Vascular graft infection (VGI) is a serious complication after implantation of arterial vascular grafts. Optimal surgical and pathogen-specific antimicrobial treatment regimens for VGI are largely unknown. We evaluated patients with arterial VGI according to onset, location, microbiological and imaging characteristics, surgical and antimicrobial treatment and performed an outcome evaluation. Methods Consecutive patients with VGI treated in two hospitals from 2010 through 2020 were retrospectively analyzed. Uniform definition criteria and standardized outcome evaluation were applied. Logistic regression was used for multiple analysis, survival analysis was performed with Kaplan-Meier analysis and log-rank test. Results Seventy-eight patients with VGI were included, consisting of 30 early-onset (<8 weeks after graft implantation) and 48 late-onset cases, involving 49 aortic and 29 peripheral grafts. The median time from initial implantation to diagnosis of VGI was significantly longer in aortic than peripheral VGIs (363 days vs. 56 days, p = 0.018). Late-onset VGI (OR 7.3, p = 0.005) and the presence of surgical site infection/complication (OR 8.21, p = 0.006) were independent risk factors for treatment failure. Surgical site infection/complication was associated with higher risk for early-onset VGI (OR 3.13, p = 0.040). Longer infection-free survival was observed in cases where the infected graft was surgically removed (p = 0.037). Conclusion This study underlines the importance of timely diagnosis of VGI and preventing surgical site infections/complications at graft implantation. It highlights the complexity of infection eradication, especially of late-onset infections, and the importance of adequate antimicrobial and surgical treatment.

Impact of inadequate empirical antibiotic treatment on outcome of non-critically ill children with bacterial infections

BackgroundThe impact of inadequate empirical antibiotic treatment on patient outcomes and hospitalization duration for non-life-threatening infections in children remains poorly understood. We aimed to assess the effects of inadequate empirical antibiotic treatment on these factors in pediatric patients.MethodsThe medical records of children admitted for infectious diseases with bacteria isolated from sterile sites between 2018 and 2020 were retrospectively reviewed. Patients who received adequate empirical treatment were compared with those who received inadequate treatment in terms of demographic, clinical, and laboratory variables.ResultsForty-eight patients who received inadequate empirical antimicrobial treatment were compared to 143 patients who received adequate empirical treatment. Inadequate empirical antimicrobial treatment did not significantly affect the length of hospital stay or the incidence of complications in non-critically ill children with bacterial infections. Younger age and underlying renal abnormalities were identified as risk factors for inadequate antimicrobial treatment, while associated bacteremia was more common in the adequate antimicrobial treatment group.Conclusionsinadequate antibiotic treatment did not affect the outcomes of non-critically ill children with bacterial infectious diseases. Therefore, routine empirical broad-spectrum treatment may not be necessary for these cases, as it can lead to additional costs and contribute to antibiotic resistance. Larger prospective studies are needed to confirm these findings.

The effect of duration of antimicrobial treatment for bacteremia in critically ill patients on in-hospital mortality – Retrospective double center analysis

PurposeExcessive duration of antibiotic treatment is a major factor for inappropriate antibiotic consumption. Although in some instances shorter antibiotic courses are as efficient as longer ones, no specific recommendations as to the duration of antimicrobial treatment for bloodstream infections currently exist. In the present study, we investigated the effect of antibiotic treatment duration on in-hospital mortality using retrospective data from two cohorts that included patients with bacteremia at two Swiss tertiary Intensive Care Units (ICUs). Materials and methodsOverall 8227 consecutive patients requiring ICU admission were screened for bacteremia between 01/2012–12/2013 in Lausanne and between 07/2016–05/2017 in Bern. Patients with an infection known to require prolonged treatment or having single positive blood culture with common contaminant pathogens were excluded. The primary outcome of interest was the time from start of antimicrobial treatment to in-hospital death or hospital discharge, whichever comes first. The predictor of interest was adequate antimicrobial treatment duration, further divided into shorter (≤10 days) and longer (>10 days) durations. A time-dependent Cox model and a cloning approach were used to address immortality bias. The secondary outcomes were the median duration of antimicrobial treatment for patients with bacteremia overall and stratified by underlying infectious syndrome and pathogens in the case of secondary bacteremia. ResultsOut of the 707 patients with positive blood cultures, 382 were included into the primary analysis. Median duration of antibiotic therapy was 14 days (IQR, 7–20). Most bacteremia (84%) were monomicrobial; 18% of all episodes were primary bacteremia. Respiratory (28%), intra-abdominal (23%) and catheter infections (17%) were the most common sources of secondary bacteremia. Using methods to mitigate the risk of confounding associated with antibiotic treatment durations, shorter versus longer treatment groups showed no differences in in-hospital survival (time-dependent Cox-model: HR 1.5, 95% CI (0.8, 2.7), p = 0.20; Cloning approach: HR 1.0, 95% CI (0.7,1.5) p = 0.83). Sensitivity analyses showed that the interpretation did not change when using a 7 days cut-off. ConclusionsIn this restrospective study, we found no evidence for a survival benefit of longer (>10 days) versus shorter treatment course in ICU patients with bacteremia. Trial registrationThe study was retrospectively registered on clinicatrials.gov (NCT05236283), 11 February 2022. The respective cantonal ethics commission (KEK Bern # 2021–02302) has approved the study.

Sternotomy closure using negative pressure wound therapy after heart transplantation

Summary Background Deep sternal wound infection (DSWI) after orthotopic heart transplantation (OHT) is not a common but known complication and carries high mortality and morbidity rates. This report identifies a successful management strategy for recurrent DSWI, and it is a valuable addition to the medical literature supporting the management of sternal wound infections (SWI) along with negative pressure wound therapy (NPWT). Case presentation This report describes the successful management of recurrent DSWI after OHT in a 52-year-old patient. We performed secondary sternotomy closure along with NPWT for the immunosuppressed patient. Conclusion Our case demonstrates that a combination of reduced immunosuppression, adequate antimicrobial treatment, and NPWT can effectively treat complicated DSWI.

Feasibility of 16S rRNA sequencing for cerebrospinal fluid microbiome analysis in cattle with neurological disorders: a pilot study

Bacterial infection of the central nervous system (CNS) in cattle requires prompt and adequate antimicrobial treatment. The current gold standard for antemortem etiological diagnosis is cerebrospinal fluid (CSF) culture, which often yields false negative results. CSF has long been considered a sterile district in healthy patients, but this notion has been recently challenged. For this pilot study, we used 16S rRNA gene sequencing to investigate the microbial composition of CSF of cattle presenting with CNS disorders and to compare it between subjects with CNS infections and with CNS disorders of other nature. The study sample was 10 animals: 4 presenting with CNS infectious-inflammatory diseases and 6 with other CNS disorders, based on definitive diagnosis. Since the initial round of a standard 16S rRNA PCR did not yield sufficient genetic material for sequencing in any of the samples, the protocol was modified to increase its sensitivity. Bacterial genetic material was identified in 6 animals and 2 groups were formed: an infectious inflammatory (n = 3) and a noninfectious inflammatory group (n = 3). The most frequently expressed bacterial families were Pseudomonadaceae (44.61%), Moraxellaceae (19.54%), Mycobacteriaceae (11.80%); the genera were Pseudomonas (45.42%), Acinetobacter (19.91%), Mycobacterium (12.01%). There were no detectable differences in the CSF microbial composition of the samples from the two groups. Sequencing of bacterial DNA present in the CSF was possible only after increasing PCR sensitivity. The results of 16S rRNA sequencing showed the presence of a microbial community in the CSF in cattle with neurological disorders. Further studies, in which CSF samples from healthy animals and samples from the environment are included as controls, are needed.

Establishment and validation of a nomogram to predict the in-hospital death risk of nosocomial infections in cancer patients

BackgroundAttributed to the immunosuppression caused by malignancy itself and its treatments, cancer patients are vulnerable to developing nosocomial infections. This study aimed to develop a nomogram to predict the in-hospital death risk of these patients.MethodsThis retrospective study was conducted at a medical center in Northwestern China. The univariate and multivariate logistic regression analyses were adopted to identify predictive factors for in-hospital mortality of nosocomial infections in cancer patients. A nomogram was developed to predict the in-hospital mortality of each patient, with receiver operating characteristic curves and calibration curves being generated to assess its predictive ability. Furthermore, decision curve analysis (DCA) was also performed to estimate the clinical utility of the nomogram.ResultsA total of 1,008 nosocomial infection episodes were recognized from 14,695 cancer patients. Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (15.5%) was the most predominant causative pathogen. Besides, multidrug-resistant strains were discovered in 25.5% of cases. The multivariate analysis indicated that Eastern Cooperative Oncology Group Performance Status 3–4, mechanical ventilation, septic shock, hypoproteinemia, and length of antimicrobial treatment < 7 days were correlated with higher in-hospital mortality. Patients who received curative surgery were correlated with favorable survival outcomes. Ultimately, a nomogram was constructed to predict the in-hospital mortality of nosocomial infections in cancer patients. The area under the curve values of the nomogram were 0.811 and 0.795 in the training and validation cohorts. The calibration curve showed high consistency between the actual and predicted in-hospital mortality. DCA indicated that the nomogram was of good clinical utility and more credible net clinical benefits in predicting in-hospital mortality.ConclusionsNosocomial infections stay conjoint in cancer patients, with gram-negative bacteria being the most frequent causative pathogens. We developed and verified a nomogram that could effectively predict the in-hospital death risk of nosocomial infections among these patients. Precise management of high-risk patients, early recognition of septic shock, rapid and adequate antimicrobial treatment, and dynamic monitoring of serum albumin levels may improve the prognosis of these individuals.

Management of pneumonia in critically ill patients.

Severe pneumonia is associated with high mortality (short and long term), as well as pulmonary and extrapulmonary complications. Appropriate diagnosis and early initiation of adequate antimicrobial treatment for severe pneumonia are crucial in improving survival among critically ill patients. Identifying the underlying causative pathogen is also critical for antimicrobial stewardship. However, establishing an etiological diagnosis is challenging in most patients, especially in those with chronic underlying disease; those who received previous antibiotic treatment; and those treated with mechanical ventilation. Furthermore, as antimicrobial therapy must be empiric, national and international guidelines recommend initial antimicrobial treatment according to the location's epidemiology; for patients admitted to the intensive care unit, specific recommendations on disease management are available. Adherence to pneumonia guidelines is associated with better outcomes in severe pneumonia. Yet, the continuing and necessary research on severe pneumonia is expansive, inviting different perspectives on host immunological responses, assessment of illness severity, microbial causes, risk factors for multidrug resistant pathogens, diagnostic tests, and therapeutic options.

Molecular Evidence for Flea-Borne Rickettsiosis in Febrile Patients from Madagascar.

Rickettsiae may cause febrile infections in humans in tropical and subtropical regions. From Madagascar, no molecular data on the role of rickettsioses in febrile patients are available. Blood samples from patients presenting with fever in the area of the capital Antananarivo were screened for the presence of rickettsial DNA. EDTA (ethylenediaminetetraacetic acid) blood from 1020 patients presenting with pyrexia > 38.5 °C was analyzed by gltA-specific qPCR. Positive samples were confirmed by ompB-specific qPCR. From confirmed samples, the gltA amplicons were sequenced and subjected to phylogenetic analysis. From five gltA-reactive samples, two were confirmed by ompB-specific qPCR. The gltA sequence in the sample taken from a 38-year-old female showed 100% homology with R. typhi. The other sample taken from a 1.5-year-old infant was 100% homologous to R. felis. Tick-borne rickettsiae were not identified. The overall rate of febrile patients with molecular evidence for a rickettsial infection from the Madagascan study site was 0.2% (2/1020 patients). Flea-borne rickettsiosis is a rare but neglected cause of infection in Madagascar. Accurate diagnosis may prompt adequate antimicrobial treatment.

Mycobacterium setense isolated from a cat with atypical mycobacterial panniculitis.

Atypical mycobacterial panniculitis was diagnosed in a cat. Mycobacterium setense was identified as causative agent by 16 S rRNA gene sequence analysis. This a gram-positive rod-shaped acid-fast bacterium belonging to Mycobacterium fortuitum group was never reported before in diseased animals. Resistance to doxycycline and clarithromycin was detected. During treatment with pradofloxacin, additional resistance to fluoroquinolones developed which was due to a mutation in the gyrase gene gyrA (S90W exchange). Despite of antimicrobial treatment for 33 months the patient did not fully recover. Species identification and susceptibility testing for choosing adequate antimicrobial treatment is recommended in cases of feline mycobacterial panniculitis.

Ventilator-associated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study

BackgroundThe data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons.ResultsAmong 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42–56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8–16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients (p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups.ConclusionsPatients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.

Non-antibiotic pharmaceutical agents as antibiotic adjuvants

The emergence of multidrug-resistant bacteria is a global public health issue, which severely hinders clinicians in providing patients with adequate antimicrobial treatment regimens. The strategy of drug repurposing is an emerging strategy in antimicrobial chemotherapy, during which new pharmacological uses are identified for drugs already approved. The aim of our present study was to assess the adjuvant properties of several existing and widely-used pharmacological agents against bacteria in combination with reference antibiotics. Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603 were selected for our experiments. The minimum inhibitory concentrations (MICs) of the tested compounds were determined using the broth microdilution method, while a MIC reduction assay was performed to ascertain the effect of the tested compounds on the MICs of standard antibiotics (ciprofloxacin and gentamicin). Eight tested compounds (namely atorvastatin, celecoxib, clotrimazole, diclofenac-epolamine, ivermectin, lidocaine, mebendazole and terbinafine) showed antibacterial activity on the tested bacterial strains and several agents presented with various degrees of adjuvant (MIC-reducing) properties. Further experiments involving the screening of additional pharmaceutical compounds for their secondary antibacterial and adjuvant properties are warranted.

Mortality after Delay of Adequate Empiric Antimicrobial Treatment of Bloodstream Infection.

Background: Timely empiric antimicrobial therapy is one of the cornerstones of the management of suspected bloodstream infection (BSI). However, studies about the effects of empiric therapy on mortality have reported inconsistent results. The objective of this study was to estimate the effect of delay of appropriate empiric therapy on early mortality in patients with BSI. Methods: Data for the propensity score matching (PSM) study were obtained from a cohort of patients with BSI. Inadequate empiric treatment was defined as in vitro resistance to the antimicrobial regimen administered <6 h after blood cultures were taken. The primary outcome measure was 14-day mortality. Thirty-day mortality and median length of stay (LOS) were secondary outcomes. PSM was applied to control for confounding. Results: Of a total of 893 included patients with BSI, 35.7% received inadequate initial empiric treatment. In the PSM cohort (n = 334), 14-day mortality was 9.6% for inadequate antibiotic treatment, compared to. 10.2% in adequate empiric treatment (p = 0.85). No prolonged median LOS was observed in patients who initially received inadequate therapy (10.5 vs. 10.7 days, p = 0.89). Conclusions: In this study, we found no clear effect of inadequate empirical treatment on mortality in a low-risk BSI population. The importance of early empiric therapy compared to other determinants, may be limited. This may not apply for specific subpopulations, e.g., patients with sepsis.

Neisseira meningitidis Serogroup W causing primary meningococcal septic arthritis in a toddler and review of the literature

Since 2009, there has been a serious increase in the number of meningococcal infections in Europe caused by the serotype W meningococcus (MenW:cc11). Invasive meningococcal disease is typically known to cause severe sepsis or meningitiswith high overall mortality rates of 10% despite adequate antimicrobial treatment. Focal infections such as arthritis incidentally occur as a complication of systemic disease. Method We describe a rare case of primary meningococcal W135 arthritis in a 2-year-old patient. Results Arthrocentesis of the right Ankle while patient was under anesthesia, yielded grossly purulent fluid, so we made arthrotomy and drainage. The culture from synovial fluid revealed N. meningitidis.The status of the patient improved after surgical drainage and intravenous antibiotic therapy. She recovered completely after 1 month. Discussion.Atypical clinical presentation is associated with higher case fatality rates and can lead to misdiagnoses.an unusual presentation of invasive meningococcal infection and the early identification of the bacteria, combined with the correct treatment, prevent the complications and even death.

Fournier's Gangrene: 10-Year Experience of a Plastic Surgery and Burns Department at a Tertiary Hospital.

Fournier gangrene is a polymicrobial life threatening infection of perineal subcutaneous soft tissues with its point of originin urologic, colorectal or skin diseases. Although more frequent in elderly and men, it can affect all genders and age groups. Perianalabscess, diabetes mellitus and Escherichia coli are the most frequent cause, predisposing comorbidity, and microorganism found intissue culture analysis respectively. The objective of this study was to describe the experience of a Plastic Surgery Department of atertiary Hospital in reconstructing Fournier's gangrene perineal defects and its detailed demography. The sample is composed of all patients with Fournier gangrene admitted in the Plastic Surgery and BurnsDepartment. The authors retrospectively collected and analyzed demographic and clinical data during a period of 10 years includinggender, age, length of stay, cause, number of debridements, predisposing factors, microbial culture results, surgical reconstructivetechniques and its associated complications, additional surgical procedures and outcomes. Fifteen patients were identified: 14 males (93%) and one female (7%); mean age was 66.9 years (range: 46 - 86); mean,length of stay was 46.8 days (range: 20 - 71 days) and mean number of debridements was 3.3 (range: 1 - 4). The most frequent predisposing factor was diabetes mellitus, the major cause was perianal (n = 2) and skin abscess (n = 2). Eight (53.3%) patients had no identifiable source of Fournier gangrene. Various types of reconstructive techniques were employed; and 5 additional surgical interventions(33.3%) were undertaken (one cystostomy, two orchidectomy, two ileostomy); six patients (40%) presented reconstructive techniquecomplications with adequate final outcome. In contrast with the literature, where Escherichia coli was the most frequently isolated agent, Staphylococcus aureus wasthe most frequent microorganism found in tissue biopsy/pus collection analysis. A higher than expected number of patients (n = 8) hadno identifiable source of Fournier gangrene. This findings can be explained by the retrospective non-multicentre study limitation, witha potencial source of bias patients that were transferred from other hospitals in advanced stage, without point of origin of Fournier'sgangrene identified. Early recognition and extensive necrotic tissue debridement, along with prompt and adequate antimicrobial treatment, arethe mainstay of Fournier gangrene management, thus reducing morbidity and mortality in these patients. Surgical reconstruction challenges derived from this condition should be addressed by specialized teams due to the risk of dysfunctional sequelae and conspicuousdeformities. Taking in account the single-center and retrospective observational character of the present study, these premises requireproper validation from a multicenter prospective study.

New antimicrobial options for the management of complicated intra-abdominal infections.

Complicated intra-abdominal infections (cIAIs) are a common cause of morbidity and mortality in surgical patients. Optimal management of cIAI requires early source control in combination with adequate antimicrobial treatment and aggressive fluid resuscitation. cIAIs are mainly caused by Gram-negative bacilli and anaerobes. Broad-spectrum single-agent or combination drug regimens against these microorganisms are the mainstay of therapy. However, development of antimicrobial resistance has become an increasingly large concern: multidrug-resistant organisms are associated with a higher rate of inadequate antimicrobial therapy, which in turn is associated with higher mortality rate, longer hospital stay, and increased cost compared to adequate antimicrobial therapy. In this mini-review, we discuss the effectiveness of several new antimicrobial agents, recently approved or in advanced phases of clinical development, for the treatment of cIAIs, including the new beta-lactam and beta-lactamase inhibitor combinations (ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, aztreonam/avibactam), siderophore cephalosporins (cefiderocol), aminoglycosides (plazomicin), and tetracyclines (eravacycline).

A case-control study on the clinical impact of ventilator associated tracheobronchitis in adult patients who did not develop ventilator associated pneumonia

ObjectivesThe main objective was to determine whether ventilator-associated tracheobronchitis (VAT) is related to increased length of ICU stay. Secondary endpoints included prolongation of hospital stay, as well as, ICU and hospital mortality. DesignA retrospective matched case-control study. Each case was matched with a control for duration of ventilation (±2 days until development of ventilator-associated tracheobronchitis), disease severity (Acute Physiology and Chronic Health Evaluation II) at admission ±3, diagnostic category and age ±10 years. PatientsCritically ill adults admitted to a polyvalent 30-beds ICU with the diagnosis of VAT in the period 2013–2016. Main resultsWe identified 76 cases of VAT admitted to our ICU during the study period. No adequate controls were found for 3 patients with VAT. There were no significant differences in demographic characteristics, reasons for admission and comorbidities. Patients with VAT had a longer ICU length of stay, median 22 days (14–35), compared to controls, median 15 days (8–27), p=0.02. Ventilator days were also significantly increased in VAT patients, median 18 (9–28) versus 9 days (5–16), p=0.03. There was no significant difference in total hospital length of stay 40 (28–61) vs. 35days (23–54), p=0.32; ICU mortality (20.5 vs. 31.5% p=0.13) and hospital mortality (30.1 vs. 43.8% p=0.09). We performed a subanalysis of patients with microbiologically proven VAT receiving adequate antimicrobial treatment and did not observe significant differences between cases and the corresponding controls. ConclusionsVAT is associated with increased length of intensive care unit stay and longer duration of mechanical ventilation. This effect disappears when patients receive appropriate empirical treatment.

Characterization of antimicrobial resistance mechanisms in carbapenem-resistant Pseudomonas aeruginosa carrying IMP variants recovered from a Mexican Hospital.

PurposePseudomonas aeruginosa infections in hospitals constitute an important problem due to the increasing multidrug resistance (MDR) and carbapenems resistance. The knowledge of resistance mechanisms in Pseudomonas strains is an important issue for an adequate antimicrobial treatment. Therefore, the objective was to investigate other antimicrobial resistance mechanisms in MDR P. aeruginosa strains carrying blaIMP, make a partial plasmids characterization, and determine if modifications in oprD gene affect the expression of the OprD protein.MethodologySusceptibility testing was performed by Kirby Baüer and by Minimum Inhibitory Concentration (presence/absence of efflux pump inhibitor); molecular typing by Pulsed-field gel electrophoresis (PFGE), resistance genotyping and integrons by PCR and sequencing; OprD expression by Western blot; plasmid characterization by MOB Typing Technique, molecular size by PFGE-S1; and blaIMP location by Southern blot.ResultsAmong the 59 studied P. aeruginosa isolates, 41 multidrug resistance and carbapenems resistance isolates were detected and classified in 38 different PFGE patterns. Thirteen strains carried blaIMP; 16 blaGES and four carried both genes. This study centered on the 17 strains har-boring blaIMP. New variants of β-lactamases were identified (blaGES-32, blaIMP-56, blaIMP-62) inside of new arrangements of class 1 integrons. The presence of blaIMP gene was detected in two plasmids in the same strain. The participation of the OprD protein and efflux pumps in the resistance to carbapenems and quinolones is shown. No expression of the porin OprD due to stop codon or IS in the gene was found.ConclusionsThis study shows the participation of different resistance mechanisms, which are reflected in the levels of MIC to carbapenems. This is the first report of the presence of three new variants of β-lactamases inside of new arrangements of class 1 integrons, as well as the presence of two plasmids carrying blaIMP in the same P. aeruginosa strain isolated in a Mexican hospital.

Estudio caso-control del impacto clínico de la traqueobronquitis asociada a la ventilación mecánica en pacientes adultos, que no desarrollan neumonía asociada a ventilación mecánica

ObjectivesThe main objective was to determine whether ventilator-associated tracheobronchitis (VAT) is related to increased length of ICU stay. Secondary endpoints included prolongation of hospital stay, as well as, ICU and hospital mortality. DesignA retrospective matched case-control study. Each case was matched with a control for duration of ventilation (± 2 days until development of ventilator-associated tracheobronchitis), disease severity (Acute Physiology and Chronic Health Evaluation II) at admission ± 3, diagnostic category and age ±10 years. PatientsCritically ill adults admitted to a polyvalent 30-beds ICU with the diagnosis of VAT in the period 2013-2016. Main resultsWe identified 76 cases of VAT admitted to our ICU during the study period. No adequate controls were found for 3 patients with VAT. There were no significant differences in demographic characteristics, reasons for admission and comorbidities. Patients with VAT had a longer ICU length of stay, median 22 days (14-35), compared to controls, median 15 days (8-27), p=.02. Ventilator days were also significantly increased in VAT patients, median 18 (9-28) versus 9 days (5-16), p=.03. There was no significant difference in total hospital length of stay 40 (28-61) vs. 35days (23-54), p=.32; ICU mortality (20.5 vs. 31.5% p=.13) and hospital mortality (30.1 vs. 43.8% p=.09). We performed a subanalysis of patients with microbiologically proven VAT receiving adequate antimicrobial treatment and did not observe significant differences between cases and the corresponding controls. ConclusionsVAT is associated with increased length of intensive care unit stay and longer duration of mechanical ventilation. This effect disappears when patients receive appropriate empirical treatment.

Persistence of Innate Immune Pathways in Late Stage Human Bacterial and Fungal Keratitis: Results from a Comparative Transcriptome Analysis.

Microbial keratitis (MK) is a major cause of blindness worldwide. Despite adequate antimicrobial treatment, tissue damage can ensue. We compared the human corneal transcriptional profile in late stage MK to normal corneal tissue to identify pathways involved in pathogenesis. Total RNA from MK tissue and normal cadaver corneas was used to determine transcriptome profiles with Illumina HumanHT-12 v4 beadchips. We performed differential expression and network analysis of genes in bacterial keratitis (BK) and fungal keratitis (FK) compared with control (C) samples. Results were validated by RTqPCR for 45 genes in an independent series of 183 MK patients. For the microarray transcriptome analysis, 27 samples were used: 12 controls, 7 BK culture positive for Streptococcus pneumoniae (n = 6), Pseudomonas aeruginosa (n = 1), and 8 FK, culture positive for Fusarium sp. (n = 5), Aspergillus sp. (n = 2), or Lasiodiplodia sp. (n = 1). There were 185 unique differentially expressed genes in BK, 50 in FK, and 339 common to both [i.e., genes with fold-change (FC) < −4 or ≥4 and false discovery rate (FDR) adjusted P < 0.05]. MMP9 had the highest FC in BK (91 FC, adj p = 3.64 E-12) and FK (FC 64, adj. p = 6.10 E-11), along with other MMPs (MMP1, MMP7, MMP10, MMP12), pro-inflammatory cytokines (IL1B, TNF), and PRRs (TLR2, TLR4). HIF1A and its induced genes were upregulated uniquely in BK. Immune/defense response and extracellular matrix terms were the most enriched Gene Ontology terms in both BK and FK. In the network analysis, chemokines were prominent for FK, and actin filament reorganization for BK. Microarray and RTqPCR results were highly correlated for the same samples tested with both assays, and with the larger RTqPCR series. In conclusion, we found a great deal of overlap in the gene expression profile of late stage BK and FK, however genes unique to fungal infection highlighted a corneal epithelial wound healing response and for bacterial infection the prominence of HIF1A-induced genes. These sets of genes may provide new targets for future research into therapeutic agents.

Prevalence and Antimicrobial Susceptibility of Uropathogens Isolated from Ambulatorial and Nosocomial Infections at Nova Friburgo, Rio de Janeiro, Brazil.

Justificativa e Objetivos: Infecção do Trato Urinário (ITU) é a segunda infecção mais comum, geralmente causada por enterobactérias, principalmente Escherichia coli. Estes microrganismos tem apresentado resistência antimicrobiana para as principais drogas utilizadas para tratar ITU em diferentes partes do mundo. Entretanto, estudos prévios sobre a prevalência e susceptibilidade antimicrobiana regional não foram publicados. Este trabalho objetivou investigar a prevalência e susceptibilidade aos antimicrobianos apresentado por bactérias associadas a ITU de pacientes ambulatoriais ou nosocomiais atendidos ou internados em um hospital em Nova Friburgo, Rio de Janeiro, Brasil. Métodos: Um estudo retrospectivo avaliou a prevalência e a susceptibilidade antimicrobiana de urinoculturas positivas de pacientes ambulatoriais e nosocomiais entre Julho de 2010 a Junho de 2014. Resultados: Dos pacientes ambulatoriais, o microrganismo mais prevalente foi Escherichia coli (76.50%), seguido por Enterobacter sp. (12.02%), e Proteus sp. (5.46%). Nas ITUs nosocomiais, as bactérias mais prevalentes foram E. coli (65.96%), Proteus sp. (7.80%), e Pseudomonas sp. (7.09%). A maioria das urinoculturas positivas foi isolada de mulheres (89.13%). A susceptibilidade antimicrobiana revelou que a maioria de E. coli isolada de pacientes ambulatoriais foi mais resistente à ampicilina (45.00%), ácido nalidíxico (37.14%), nitrofurantoína (35.71%). Dos isolados nosocomiais, E. coli foi mais resistente à ampicilina (56.69%), cefalotina, trimetoprim/sulfametoxazol (43.01%) e ciprofloxacina (33.33%). Conclusão: A resistência antimicrobiana de E. coli foi observada na maioria das ITUs, independente na origem do paciente. Estes resultados contribuirão para melhorar a seleção da terapia antimicrobiana adequada tanto para ITU ambulatorial quanto hospitalar adquiridas em nossa comunidade.