Ammar Yousif

Biofilm-Based Central Line-Associated Bloodstream Infections

Different types of central venous catheters (CVCs) have been used in clinical practice to improve the quality of life of chronically and critically ill patients. Unfortunately, indwelling devices are usually associated with microbial biofilms and eventually lead to catheter-related bloodstream infections (CLABSIs).An estimated 250,000-400,000 CLABSIs occur every year in the United States, at a rate of 1.5 per 1,000 CVC days and a mortality rate of 12-25 %. The annual cost of caring for patients with CLABSIs ranges from 296 million to 2.3 billion dollars.Biofilm formation occurs on biotic and abiotic surfaces in the clinical setting. Extensive studies have been conducted to understand biofilm formation, including different biofilm developmental stages, biofilm matrix compositions, quorum-sensing regulated biofilm formation, biofilm dispersal (and its clinical implications), and multi-species biofilms that are relevant to polymicrobial infections.When microbes form a matured biofilm within human hosts through medical devices such as CVCs, the infection becomes resistant to antibiotic treatment and can develop into a chronic condition. For that reason, many techniques have been used to prevent the formation of biofilm by targeting different stages of biofilm maturation. Other methods have been used to diagnose and treat established cases of CLABSI.Catheter removal is the conventional management of catheter associated bacteremia; however, the procedure itself carries a relatively high risk of mechanical complications. Salvaging the catheter can help to minimize these complications.In this article, we provide an overview of microbial biofilm formation; describe the involvement of various genetic determinants, adhesion proteins, organelles, mechanism(s) of biofilm formation, polymicrobial infections, and biofilm-associated infections on indwelling intravascular catheters; and describe the diagnosis, management, and prevention of catheter-related bloodstream infections.

Successful Salvage of Central Venous Catheters in Patients with Catheter-Related or Central Line-Associated Bloodstream Infections by Using a Catheter Lock Solution Consisting of Minocycline, EDTA, and 25% Ethanol

ABSTRACT In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites. In vitro and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheter in situ. Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively; P < 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.)

Role of Procalcitonin and Interleukin-6 in Predicting Cancer, and Its Progression Independent of Infection.

Procalcitonin (PCT) and Interleukin-6 (IL-6) have emerged as biomarkers for different inflammatory conditions. The purpose of the study was to evaluate the role of PCT and IL-6 as biomarkers of cancer and its progression in a large cohort of patients. This cross-sectional study included residual plasma samples collected from cancer patients, and control subjects without cancer. Levels of PCT and IL-6 were determined by Kryptor compact bioanalyzer. We identified 575 febrile cancer patients, 410 non-febrile cancer patients, and 79 non-cancer individuals. The median PCT level was lower in control subjects (0.029 ng/ml) compared to cancer patients with stage I-III disease (0.127 ng/ml) (p<0.0001) and stage IV disease (0.190 ng/ml) (p<0.0001). It was also higher in febrile cancer patients (0.310 ng/ml) compared to non-febrile cancer patients (0.1 ng/ml) (p<0.0001). Median IL-6 level was significantly lower in the control group (0 pg/ml) than in non-febrile cancer patients with stages I-III (7.376 pg/ml) or stage IV (9.635 pg/ml) (p<0.0001). Our results suggest a potential role for PCT and IL-6 in predicting cancer in non-febrile patients. In addition, PCT is useful in detecting progression of cancer and predicting bacteremia or sepsis in febrile cancer patients.

A clinical practical approach to the surveillance definition of central line-associated bloodstream infection in cancer patients with mucosal barrier injury

BACKGROUND The Centers for Disease Control and Prevention recently introduced the concept of mucosal barrier injury (MBI) in an attempt to recognize the possibility of a gastrointestinal source for certain bloodstream infections. This could underestimate the central venous catheter (CVC) as the source of central line-associated bloodstream infection (CLABSI) in cancer. The definition of catheter-related bloodstream infection (CRBSI) by the Infectious Diseases Society of America is a more specific and stringent definition that identifies the CVC as the source of infection. In our study, we compared the 2 definitions in cancer patients. METHODS We retrospectively reviewed 149 CLABSI cases that occurred at our center between January 2013 and March 2014 who had 2 simultaneously positive blood cultures drawn from the CVC and peripheral site or concurrent paired tip and blood cultures. RESULTS Of the 149 patients with CLABSI, only 70 (47%) had definite CRBSI. CRBSI was identified more commonly in non-MBI CLABSI cases than MBI CLABSI (69% vs 18%, P < .0001). CONCLUSIONS The CRBSI definition may be more accurate in identifying the catheter as the source of bloodstream infection in patients with MBI. Because CRBSI continues to occur in patients with MBI, we caution against excluding all MBI patients from CLABSI surveillance.

The influence of using antibiotic-coated peripherally inserted central catheters on decreasing the risk of central line-associated bloodstream infections

The use of peripherally inserted central catheters (PICCs) has increased over the past few years due to their less serious insertion complications. The purpose of the present study was to determine whether patients receiving PICCs impregnated with minocycline and rifampin had a lower rate of CLABSI compared with a concurrent control group of patients receiving uncoated PICCs.

Mycobacterium arupense in Cancer Patients: An Emerging Infection or a Commensal Organism.

AbstractMycobacterium arupense is a slow-growing, nonchromogenic, acid-fast bacillus. Its clinical spectrum, epidemiology, and frequency of colonization versus true infection remain unknown. We evaluated the clinical significance of M arupense and positive cultures from cancer patients.We retrospectively reviewed records of all cancer patients treated at our institution between 2007 and 2014 to identify those who had positive cultures for M arupense. Mycobacterium arupense was identified by sequencing the 16S rRNA and hsp65 genes. A total of 53patients had positive cultures, 100% of which were isolated from respiratory specimens. Of these, 7 patients met the American Thoracic Society/Infectious Diseases Society of America criteria for a definitive diagnosis of M arupense infection, 14 cases were considered to be probable infections, and 29 cases were considered to be possible infections. Of the included patients, 13 received therapy for M arupense infection and 40 did not.The outcomes of treated and untreated patients did not differ significantly. No relapses of M arupense infection. In addition, there were no M arupense-related deaths in either group.In cancer patients, M arupense appears to be mostly a commensal organism rather than a pathogen. Patients who did or did not receive treatment had similar outcomes. Validation of these findings in a larger prospective trial is warranted.

Case-Control Study of Telavancin as an Alternative Treatment for Gram-Positive Bloodstream Infections in Patients with Cancer

ABSTRACT Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CLCR) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CLCR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.)

Procalcitonin Guiding Antimicrobial Therapy Duration in Febrile Cancer Patients with Documented Infection or Neutropenia

In this analysis, we identified febrile cancer patients with documented infections or neutropenia, whose procalcitonin levels are low at baseline or decrease on antibiotics. These patients had similar outcomes in terms of mortality and relapse of infection regardless of the duration of antimicrobial therapy (less or more than 7 days).

Changing Epidemiology of Catheter-Related Bloodstream Infections in Cancer Patients

We compared the etiologic organisms of bloodstream infections (BSIs) in cancer patients with central venous catheters (CVCs) between 2 cohorts separated by more than a decade.Gram-negative organisms have become the predominant etiologic organisms of BSIs (52%); they now contribute to 41% of catheter-related BSIs (CRBSIs).Infect Control Hosp Epidemiol 2018;39:727-729.