Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Varicella zoster virus infection of the central nervous system in a tertiary care center in Lebanon.

OBJECTIVE: To describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon. METHODS: Retrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR. RESULTS: Twenty patients were identified (13 males). The average age was 49.7±22.2 years. The most common complaint was headache (n=17/20). Common comorbidities included hypertension (n=7/20) and diabetes mellitus (n=5/20). Immunosuppression was reported in two patients. Vesicles were only observed in eight patients. Altered mental status, focal neurological deficits, and fever were documented in six, two, and four patients respectively. All patients had CSF leukocytosis with lymphocytic predominance, normal CSF/serum glucose ratio, and high CSF protein. Eighteen patients had brain CT scans showing no relevant findings. Two of 12 patients with brain MRI had focal abnormalities. Unilateral temporal slow waves were observed in three of four patients who underwent electroencephalograms. Four patients had encephalitis and 16 had meningitis. Eighteen patients received an antiviral therapy. Treatment either included intravenous acyclovir or oral valacyclovir. The encephalitis and meningitis groups had comparable mean duration of treatment (13.5±6.6 vs. 12.2±5.4, respectively). All admitted patients showed clinical cure with no reported neurological sequelae. CONCLUSION: VZV infection should be suspected in any patient with signs and symptoms of viral meningitis or encephalitis, irrespective of age, immune status, presence or absence of vesicles, fever, or neck stiffness.

Progressive multifocal leukoencephalopathy in patients receiving rituximab and cyclophosphamide after haplo-identical T-cell replete transplantation and review of the literature.

John Cunningham virus (JCV) reactivation, occurring mainly in immunocompromised patients, leads to progressive multifocal leukoencephalopathy, an uncommon but lethal disease. JCV reactivation after T-cell replete haploidentical stem cell transplantation, in the pre-cyclophosphamide era, is poorly represented in the literature. We therefore describe two cases of acute myeloid leukemia who developed JCV reactivation after receiving cyclophosphamide and rituximab post haploidentical stem cell transplantation, and review the literature, aiming to a better understanding of the disease course and its risk factors.

Controversies in Candida management.

Invasive candidiasis (IC) is associated with increased morbidity and mortality. Although advances in diagnosis and management of this infection have been reached, there remain several controversies. The aim of this review is to tackle some of these controversies and shed light on studies that support the different sides of the arguments. Regarding central line-associated candidaemia, the current evidence appears to be more in favour of early central line removal whenever possible. Otherwise, antifungal agents such as echinocandins or polyenes should be the preferred agents. In the setting of infection with Candida parapsilosis and in light of the high minimum inhibitory concentrations (MICs) to echinocandins, azoles have been considered the preferred treatment agents. However, a recent study appears to indicate that empirical echinocandin use was not associated with a worse outcome when the isolated species was C. parapsilosis. Different strategies of antifungal treatment have been considered, namely prophylactic, empirical, pre-emptive or directed therapies. Whilst there is consensus on the need for prophylaxis in high-risk cancer patients, especially haematological malignancy and stem cell transplant populations, it remains debatable whether prophylaxis is of benefit in very low birthweight infants and in intensive care unit (ICU) patients. In the era of antifungal resistance and where antifungal stewardship has been advocated, pre-emptive therapy based on predictive models with various Candida risk scores and sensitive non-culture-based biomarkers such as ß-d-glucan appears to be a more cost-effective approach. Future efforts should be directed to optimise clinical predictive models and reliable biomarkers for early detection of IC.

One-year outcome following biological or mechanical valve replacement for infective endocarditis.

BACKGROUND: Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality. METHODS AND RESULTS: Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p=0.0009) and 25.3% vs 16.6% (p<.0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). CONCLUSIONS: Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.

Impact of a multidimensional infection control strategy on catheter-associated urinary tract infection rates in the adult intensive care units of 15 developing countries: findings of the International Nosocomial Infection Control Consortium (INICC).

PURPOSE: We aimed to evaluate the impact of a multidimensional infection control strategy for the reduction of the incidence of catheter-associated urinary tract infection (CAUTI) in patients hospitalized in adult intensive care units (AICUs) of hospitals which are members of the International Nosocomial Infection Control Consortium (INICC), from 40 cities of 15 developing countries: Argentina, Brazil, China, Colombia, Costa Rica, Cuba, India, Lebanon, Macedonia, Mexico, Morocco, Panama, Peru, Philippines, and Turkey. METHODS: We conducted a prospective before-after surveillance study of CAUTI rates on 56,429 patients hospitalized in 57 AICUs, during 360,667 bed-days. The study was divided into the baseline period (Phase 1) and the intervention period (Phase 2). In Phase 1, active surveillance was performed. In Phase 2, we implemented a multidimensional infection control approach that included: (1) a bundle of preventive measures, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback of CAUTI rates, and (6) feedback of performance. The rates of CAUTI obtained in Phase 1 were compared with the rates obtained in Phase 2, after interventions were implemented. RESULTS: We recorded 253,122 urinary catheter (UC)-days: 30,390 in Phase 1 and 222,732 in Phase 2. In Phase 1, before the intervention, the CAUTI rate was 7.86 per 1,000 UC-days, and in Phase 2, after intervention, the rate of CAUTI decreased to 4.95 per 1,000 UC-days [relative risk (RR) 0.63 (95% confidence interval [CI] 0.55-0.72)], showing a 37% rate reduction. CONCLUSIONS: Our study showed that the implementation of a multidimensional infection control strategy is associated with a significant reduction in the CAUTI rate in AICUs from developing countries.

Time-dependent analysis of extra length of stay and mortality due to ventilator-associated pneumonia in intensive-care units of ten limited-resources countries: findings of the International Nosocomial Infection Control Consortium (INICC).

Ventilator-associated pneumonias (VAPs) are a worldwide problem that significantly increases patient morbidity, mortality, and length of stay (LoS), and their effects should be estimated to account for the timing of infection. The purpose of the study was to estimate extra LoS and mortality in an intensive-care unit (ICU) due to a VAP in a cohort of 69,248 admissions followed for 283,069 days in ICUs from 10 countries. Data were arranged according to the multi-state format. Extra LoS and increased risk of death were estimated independently in each country, and their results were combined using a random-effects meta-analysis. VAP prolonged LoS by an average of 2·03 days (95% CI 1·52-2·54 days), and increased the risk of death by 14% (95% CI 2-27). The increased risk of death due to VAP was explained by confounding with patient morbidity.

Time-dependent analysis of length of stay and mortality due to urinary tract infections in ten developing countries: INICC findings.

OBJECTIVES: To estimate the excess length of stay (LOS) and mortality in an intensive care unit (ICU) due to a Catheter associated urinary tract infections (CAUTI), using a statistical model that accounts for the timing of infection in 29 ICUs from 10 countries: Argentina, Brazil, Colombia, Greece, India, Lebanon, Mexico, Morocco, Peru, and Turkey. METHODS: To estimate the extra LOS due to infection in a cohort of 69,248 admissions followed for 371,452 days in 29 ICUs, we used a multi-state model, including specific censoring to ensure that we estimate the independent effect of urinary tract infection, and not the combined effects of multiple infections. We estimated the extra length of stay and increased risk of death independently in each country, and then combined the results using a random effects meta-analysis. RESULTS: A CAUTI prolonged length of ICU stay by an average of 1.59 days (95% CI: 0.58, 2.59 days), and increased the risk of death by 15% (95% CI: 3, 28%). CONCLUSIONS: A CAUTI leads to a small increased LOS in ICU. The increased risk of death due to CAUTI may be due to confounding with patient morbidity.

Pyogenic spondylodiscitis: an overview.

Although uncommon, spontaneous and postoperative pyogenic spondylodiscitis entail major morbidity and may be associated with serious long-term sequelae. A review of the literature was done to advance our understanding of the diagnosis, treatment, and outcome of these infections. The principles of conservative treatment are to establish an accurate microbiological diagnosis, treat with appropriate antibiotics, immobilize the spine, and closely monitor for spinal instability and neurological deterioration. The purpose of surgical treatment is to obtain multiple intraoperative cultures of bone and soft tissue, perform a thorough debridement of infected tissue and decompression of neural structures, and reconstruct the unstable spinal column with bone graft with or without concomitant instrumentation. Appropriate management requires aggressive medical treatment and, at times, surgical interventions. If recognized early and treated appropriately, a full recovery can often be expected. Therefore, clinicians should be aware of the clinical presentation of such infections to improve patient outcome.

Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults.

Referral bias occurs because of the clustering of patients at tertiary care centers. This may result in the distortion of observed clinical manifestations of rare diseases. This analysis evaluates the effect of referral bias on the epidemiology of infective endocarditis (IE) in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). This is a prospective multicenter cohort study comparing transferred and non-transferred patients with IE. Factors independently associated with transfer status were evaluated using multivariable logistic regression. A total of 2,760 patients were included in the analysis, of which 1,164 (42.2%) were transferred from other medical centers. Transferred patients more often underwent surgery for IE (odds ratio [OR] = 2.5; 95% confidence interval [CI] 1.9-3.2). They were also more likely to have complications such as stroke (OR = 1.5; 95% CI 1.3-1.9), heart failure (OR = 1.4; 95% CI 1.1-1.6), and new valvular regurgitation (OR = 1.3; 95% CI 1.1-1.6). The in-hospital mortality rates were similar in both groups. Patients with IE who require surgery and suffer complications are referred to tertiary hospitals more frequently than patients with an uncomplicated course. Hospital transfer has no obvious effect on the in-hospital mortality. Referral bias should be taken into consideration when describing the clinical spectrum of IE.

International Nosocomial Infection Control Consortium (INICC) report, data summary for 2003-2008, issued June 2009.

We report the results of the International Infection Control Consortium (INICC) surveillance study from January 2003 through December 2008 in 173 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study, using Centers for Disease Control and Prevention (CDC) US National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infection, we collected prospective data from 155,358 patients hospitalized in the consortium's hospital ICUs for an aggregate of 923,624 days. Although device utilization in the developing countries' ICUs was remarkably similar to that reported from US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were markedly higher in the ICUs of the INICC hospitals: the pooled rate of central venous catheter (CVC)-associated bloodstream infections (BSI) in the INICC ICUs, 7.6 per 1000 CVC-days, is nearly 3-fold higher than the 2.0 per 1000 CVC-days reported from comparable US ICUs, and the overall rate of ventilator-associated pneumonia (VAP) was also far higher, 13.6 versus 3.3 per 1000 ventilator-days, respectively, as was the rate of catheter-associated urinary tract infection (CAUTI), 6.3 versus 3.3 per 1000 catheter-days, respectively. Most strikingly, the frequencies of resistance of Staphylococcus aureus isolates to methicillin (MRSA) (84.1% vs 56.8%, respectively), Klebsiella pneumoniae to ceftazidime or ceftriaxone (76.1% vs 27.1%, respectively), Acinetobacter baumannii to imipenem (46.3% vs 29.2%, respectively), and Pseudomonas aeruginosa to piperacillin (78.0% vs 20.2%, respectively) were also far higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 23.6% (CVC-associated bloodstream infections) to 29.3% (VAP).

Molecular characterisation of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. isolates at a tertiary-care centre in Lebanon.

The prevalence of bla CTX-M, bla TEM and bla SHV genes among extended-spectrum beta-lactamase (ESBL)-producing clinical isolates of Escherichia coli (n = 50) and Klebsiella spp. (n = 50) from Lebanon was 96%, 57% and 67%, and 40%, 82% and 84%, respectively. Genotyping revealed that the clonal diversity was unrelated to the presence of bla genes. Sequence analysis of 16 selected isolates identified the bla CTX-M-15, bla TEM-1, bla OXA-1 and six bla SHV genes, as well as the gene encoding the quinolone-modifying enzyme AAC(6')-Ib-cr. The genes encoding CTX-M-15 and AAC(6')-Ib-cr were carried on a 90-kb plasmid of the pC15-1a or pCTX-15 type, which transferred both ESBL production and quinolone resistance from donors to transconjugants.

Leptotrichia endocarditis: report of two cases from the International Collaboration on Endocarditis (ICE) database and review of previous cases.

Leptotrichia species typically colonize the oral cavity and genitourinary tract. We report the first two cases of endocarditis secondary to L. goodfellowii sp. nov. Both cases were identified using 16S rRNA gene sequencing. Review of the English literature revealed only two other cases of Leptotrichia sp. endocarditis.

Fatal brain infection caused by Aspergillus glaucus in an immunocompetent patient identified by sequencing of the ribosomal 18S-28S internal transcribed spacer.

Cerebral aspergillosis has rarely been reported in immunocompetent patients. We herein describe a unique case of cerebral aspergillosis in a healthy adult that led to his death despite aggressive antifungal therapy. Sequencing of ribosomal 18S-28S internal transcribed spacer identified the organism as Eurotium herbariorum, the teleomorph of Aspergillus glaucus.

Prepatellar Brucella melitensis bursitis: case report and literature review.

Bursal infection is an uncommon clinical presentation of brucellosis. We herein report a case of Brucella melitensis bursitis that was successfully treated. Other reported cases of brucella bursitis were reviewed. A high degree of suspicion in the right clinical setting is required for the diagnosis of brucella bursitis.

Asymptomatic Mycobacterium xenopi lung abscess in an immunocompetent male without pre-existing lung pathology.

Like other non-tuberculous mycobacteria, Mycobacterium xenopi infects more commonly patients with altered immune defenses. In immunocompetent individuals, infection with M. xenopi has been described in the setting of underlying lung disease. We here report the first case of M. xenopi lung abscess in a previously healthy patient with no known predisposing factors who was successfully treated with rifampin, isoniazid and ethambutol.

Seroprevalence of toxocariasis in Lebanon: a pilot study.

Toxocariasis is a common helminthic infection that has a worldwide distribution. However, data from Lebanon about the prevalence of this infection are non-existent. We conducted a Toxocara seroprevalence study with 150 subjects attending the outpatient clinics at the American University of Beirut Medical Center between May and June 2004. Serum specimens were tested for anti-Toxocara antibodies by enzyme-linked immunosorbent assay and confirmed by Western blot. Multivariate analysis was performed to identify risk factors for infection. The seroprevalence rate of toxocariasis was 19%. Male gender and below high school education were significantly associated with a positive serological test (odds ratios = 3.1 and 2.8, respectively). Higher numbers of persons in the household, and low family income during childhood, were significant on bivariate analysis only. Toxocariasis is common in Lebanon. A large population-based survey is needed to confirm these results.

Pseudallescheria boydii cranial osteomyelitis and subdural empyema successfully treated with voriconazole: a case report and literature review.

Described here is a case of Pseudallescheria boydii cranial osteomyelitis and subdural empyema following craniotomy, which was successfully treated with surgical debridement and voriconazole. Other reported cases of Pseudallescheria boydii osteomyelitis are reviewed. The reported case suggests that voriconazole may represent a new therapeutic option for this infection.