Antibiotic Lock Therapy Research Articles

Antibiotic lock: In vitro stability of gentamicin and sodium citrate stored in dialysis catheters at 37 °C

AbstractCatheter‐related bacteremia (CRB) is a major cause of morbidity and mortality especially among patients receiving hemodialysis. Antibiotic lock therapy represents a promising technique in the treatment of CRB. Several studies have evaluated antibiotics in combination with heparin as an interdialytic locking solution for prophylaxis of CRB. The objective of this study was to evaluate the stability of gentamicin and sodium citrate in hemodialysis catheters as an interdialytic lock. Solutions containing gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%) were prepared individually and in combination. The solutions were instilled into dialysis catheters and stored at 37 °C for 96 h. Samples were withdrawn randomly from catheter lumens at 24‐hour intervals for 4 days and stored at −20 °C until analysis. The samples were analyzed with validated, stability‐indicating HPLC assays. The luminal concentration of gentamicin 2.5 mg/mL, sodium citrate 40 mg/mL (4%), and the combination was determined on study days 0, 1, 2, 3, and 4. When gentamicin was combined with sodium citrate and stored at 37 °C in dialysis catheters, the solution showed no decrease in either the gentamicin or the sodium citrate concentrations over the 96‐hour study period. The percent of the original concentration at 96 h was 102.4±1.03 for gentamicin and 102.9±1.25 for citrate (P=0.5556). The combination of gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%) can be retained in hemodialysis catheters for at least 96 h at 37 °C with no evidence of degradation.

Outcome of attempted Hickman catheter salvage in febrile neutropenic cancer patients with Staphylococcus aureus bacteremia

There are limited data on outcomes of Hickman catheter salvage associated with Staphylococcus aureus bacteremia (SAB) in neutropenic cancer patients. We evaluated the outcome of attempted Hickman catheter salvage in these patients who were not given antibiotic lock therapy. Outcomes were retrospectively analyzed in all neutropenic cancer patients with Hickman catheter-related SAB over a 12-year period (56 episodes in 54 patients). Salvage attempts were defined as cases where the catheter was still in place 3 days after initial bacteremia. Salvage attempts were considered successful if catheter was still in place 12 weeks later without recurrent SAB or death. Of the 56 episodes, catheters were immediately removed in eight (14%), and catheter salvage was attempted in 48 (86%). Of these 48 episodes, attempted salvage was successful in 29 (60%) and failed in 14 (29%). Outcome of attempted salvage was indeterminate in five (11%) episodes. In univariate analysis, presence of external signs of catheter infection (p = 0.03), positive follow-up blood culture (p = 0.03), and methicillin resistance (p = 0.04) were significantly associated with catheter salvage failure. In multivariate analysis, presence of external signs of catheter infection (OR 12.0; p = 0.04) and methicillin resistance (OR 5.1; p = 0.04) were independently associated with catheter savage failure. In conclusion, attempted catheter salvage without antibiotic lock therapy was successful in 60% of the patients with Hickman catheter-related SAB. External signs of catheter infection and methicillin resistance were independent risk factors for catheter salvage failure.

094 Prevention of tunnelled catheter-related bacteraemia: is the solution antibiotic, heparin or citrate lock therapy associated with universal hygiene recommendations? follow-up over three consecutive periods (1999-2008)

Background and objective Catheter-related bacteraemia (CRB) is associated with an increased risk of morbidity and mortality in haemodialysis patients and accounts for 50 to 70% of catheter removals. Antibiotic lock therapy can prevent CRB in these patients but may have side-effects such as loss of hearing or acquisition of antibiotic resistance. The aim of this study was to evaluate CRB incidence over three consecutive periods using different antibiotic locks. Programme Setting and participants All adults treated by haemodialysis through a tunnelled catheter (March 1, 1999–December 31, 2008) (102 patients, 144 tunnelled catheters, 31 536 catheter-days). Quality improvement plan Universal hygiene rules, setting up of a follow-up registry, antimicrobial locks: heparin plus gentamicin (Period 1, March 1999—June 2000); heparin alone (Period 2, July 2000—December 2004); citrate (Period 3, January 2005—December 2008). Measures Repeated observations of CRB, catheter colonisation and orifice infection, analysis using simple descriptive statistics, χ 2 tests. Results Period 1: CRB incidence was 1.96 per 1000 catheters-days in 1999 and 0.29 in 2000 (p Period 2: CRB incidence increased from 0.39 per 1000 catheter-days in 2001 to 2.03 in 2002. In 2003, an audit of hygiene practices revealed non compliance with universal hygiene guidelines by the youngest nurses. After intensive nurse training, CRB incidence decreased to 0.76 per 1000 catheter-days in 2003 and to 0.63 in 2004. Period 3: CRB incidence decreased to 0.28, 0.37, 0.63, and 0 per 1000 catheter-days in 2005, 2006, 2007 and 2008, respectively. No adverse events and no catheter thrombosis were observed. Discussion and conclusions A gentamicin lock was associated with a highly significant reduction in CRB incidence but also with a highly significant emergence of bacterial resistance. Heparin alone was associated with a decrease in resistance but a higher CRB incidence despite reinforced hygiene rules. In units such as dialysis centres, gestures are repetitive and drifts in practices are quick to occur. Regular assessment is therefore essential. Since January 2003, a hygiene nurse carries out 6-monthly audits of our quality procedures in clinical and hygiene practice. The follow-up registry we have set up enables periodical re-evaluation of our procedures and the taking of corrective actions. Contexte et objectif L9infection reste la complication la plus frequente des catheters (KT) d9hemodialyse. Elle represente 50 a 70% des motifs d9ablations des KT. Le risque relatif de bacteriemie est de 7,64 (fistule, RR =1). En 1999 nous avons constate un taux eleve d9infection secondaire aux KT. Programme Un audit initial a ete realise pendant 6 mois (de mars 1999 a septembre 1999) qui a confirme un taux hautement eleve (L9incidence de bacteriemie est de 1.01 episodes pour 1000 jours/catheters pour les catheters tunnelises et 5.91 episodes pour 1000 jours/catheters pour les catheters non tunnelises). Vu les resultats de l9audit toute l9equipe medicale et paramedicale est mobilisee. Une nouvelle organisation de travail et des procedures decrivant la methode de branchement et debranchement des catheters sont redigees et validees par le CLIN. Nous avons instaure depuis 1999 une surveillance continue des infections des KT de dialyse, ce qui a permis d’evaluer nos pratiques professionnelles durant 3 periodes. Un audit est realise a chaque augmentation des taux d9infections KT. Resultats er periode (fev. 1999- juin 2000) tous les KT sont fermes par un verrou mixte (gentamicine+heparine). Des l9annee 2000 on constate une dimunition significative des bacteriemies (1,96 pour 1000 jours catheters en 1999 et 0,29 en 2000). Devant l’emergence de staphylocoque epidermidis multi resistant, nous avons arrete les verrous gentamicine en juin 2000. Il a fallut 18 mois avant de retrouver une ecologie bacterienne de 1999. eme periode (juillet 2002- dec 2004) tous les KT sont fermes par un verrou heparine seul. Nous avons constate une augmentation des infections des KT de 0.26 pour 1000 jours catheters en 2000, 0.39 en 2001 et 2.03 en 2002. Un audit realise par le CLIN montre une derive des pratiques chez les jeunes IDE. Une formation intensive des IDE pour le respect des protocoles de branchement debranchement est mise en place. L9incidence des infections des KT est a 0.76 en 2003 et 0.63 en 2004. eme periode (janv. 2005- dec. 2008) tous les KT sont fermes par un verrou citrate (46.7%). L9incidence des infections des KT est a 0.28 en 2005, 0.30 en 2006, 0,63 en 2007 et 0 en 2008. Conclusion Ce travail nous a permis de diminuer le risque d9infection secondaire aux KT. L9utilisation des verrous avec de la gentamicine a ete efficace au depend de l9augmentation de staphyloccoques multiresistants. Nous avons alerte la communaute nephrologique des 2004. Dans les services comme les centres d9hemodialyse les gestes sont repetetifs, les derives peuvent rapidement s9installer. Une evaluation reguliere nous parait indispensable. Depuis 2003 tous les 6 mois nous pratiquons un audit par l9infirmiere du CLIN avec un compte rendu et intervention.

Catheter-Related Bacteremia Caused by Staphylococcus pseudintermedius Refractory to Antibiotic-Lock Therapy in a Hemophilic Child with Dog Exposure

We describe a case of catheter-related bacteremia due to Staphylococcus pseudintermedius in a child with dog exposure. The organism was confirmed as S. pseudintermedius based on 16S rRNA gene sequence analysis and positive PCR-restriction fragment length polymorphism of the pta gene.

Successful antibiotic lock therapy in patients with refractory peritonitis

We describe two patients receiving peritoneal dialysis who experienced refractory peritonitis caused each by Gram-negative bacteria: Acinetobacter baumannii and Stenotrophomonas maltophilia. These patients did not respond to appropriate intraperitoneal antibiotic therapy. We assumed bacterial colonization in the intra-abdominal portion of the catheter with biofilm. Therefore, patients were treated with additional instillation of a ceftazidime-heparin lock into the catheter lumen after each exchange, as an adjunct to systemic antibiotic treatment which was successful. This study suggests that antibiotic lock therapy in the treatment of refractory peritonitis can be an effective method without catheter removal.

Role of Antibiotic Lock Therapy for the Treatment of Catheter-Related Bloodstream Infections

Catheter-related bloodstream infections are often difficult to treat because they are caused by organisms that embed themselves in a biofilm layer on the catheter surface, resulting in an increased resistance to antimicrobial agents. Systemic antibiotics are usually administered but, although generally effective in eliminating circulating bacteria, they frequently fail to sterilize the line, leaving the patient at a continuing risk of complications or recurrence. A successful approach to managing these infections requires making an appropriate decision regarding whether the catheter should be removed or retained using antibiotic lock therapy; and choosing the type and duration of antimicrobial therapy based on the type of organism and its resistance pattern. Studies that have evaluated antibiotic lock therapy have varied in the types of antibiotics and concentrations used, the addition of heparin to the solutions, and dwell times in the catheter lumen. Guidelines from the Infectious Diseases Society of America include use of antibiotic lock therapy as a therapeutic option for intraluminal infections when the device is not removed and, although not routine, as prophylaxis for catheter-related infection in select patient populations. However, there are no published guidelines on the concentration of heparin or antibiotics that should be used, and minimal published data on the stability of heparin combinations with antibiotics. It is to be hoped that antibiotic locks will be subject to randomized controlled trials of sufficient power to confirm or refute their use.

Antibiotic lock: In vitro stability of vancomycin and four percent sodium citrate stored in dialysis catheters at 37°C

Catheter-related bacteremia (CRB) is a major cause of morbidity and mortality especially among patients receiving hemodialysis (HD). Antibiotic lock therapy represents a promising technique in the treatment of CRB. Several studies have evaluated antibiotics in combination with heparin as an interdialytic locking solution as adjunctive therapy for CRB. The objective of this study was to evaluate the chemical stability of the vancomycin in 4% sodium citrate in HD catheters as an interdialytic lock. Vancomycin was prepared and diluted with sodium citrate 4% and stored in polyvinyl chloride syringes, 2 carbothane dialysis catheters (Hemostar) and 2 dual floating HD catheters (CardioMed). Syringes were stored at 4 degrees C or 23 degrees C and the catheters were stored in an incubator at 37 degrees C for 72 hours. Samples underwent daily chromatographic analysis and the luminal concentration of vancomycn was determined on study days 0, 1, and 3. When vancomycin is reconstituted with normal saline to achieve a concentration of 50 mg/mL, and then further diluted in 4% sodium citrate, to achieve concentrations of either 1 or 3 mg/mL, and then stored at 4 degrees C, room temperature, or 37 degrees C, solutions were observed to retain >92% of the initial concentration for the study period of 3 days. Based on the fastest degradation rate determined with 95% confidence interval, >90% is retained for 6.53 days. We conclude that vancomycin-4% citrate solutions stored in polyvinyl chloride syringes or HD catheters are not significantly affected by temperature or concentration within the 72 hours storage period. Therefore, these solutions can be anticipated to be suitable as a HD interdialytic antibiotic lock in standard HD catheters.

La estabilidad como factor para considerar en las soluciones de sellado antibiótico

Antibiotic-lock therapy (ALT) has been related to a reduction in the need for catheter withdrawal in patients with catheter-related infection. The stability of the antimicrobial solutions used in ALT has not been sufficiently investigated. A systematic literature review was performed to identify articles including studies on the stability of ALT solutions. Nine studies fulfilled the inclusion criteria requiring specific drug determination techniques, and no apparent drug alterations were observed. The main microorganisms studied were Staphylococcus spp., Pseudomonas aeruginosa, and Klebsiella pneumoniae. The antibiotics included cefazolin, ceftazidime, ciprofloxacin, colistin, gentamicin, ticarcillin/clavulanate, and vancomycin in solution, administered alone or in combinations, with or without heparin. All solutions were fairly stable except for ciprofloxacin at a concentration of 10mg/mL. Few studies applied strict criteria to assess the stability of antibiotic solutions used in ALT; hence, the currently available data are limited. Therefore, it seems advisable to include appropriate stability studies in further research on the use of ALT.

The Effectiveness of Antibiotic-Lock Therapy for the Prevention of Catheter-Related Bacteremia in Patients on Chronic Hemodialysis: Case Controlled Study in a Veteran Population

Central venous catheters (CVCs) are frequently used in patients with chronic renal failure who require long-term hemodialysis. CVCs are also known to be a major source of bloodstream infections. Though antibiotic-lock therapy (ALT) has previously been used to prevent and treat catheter-related infections, the use of ALT remains controversial due to the lack of large prospective randomized controlled trials. The purpose of this study was to evaluate the effectiveness of ALT in the prevention of catheter-related bacteremia (CRB) in a veteran population who required chronic hemodialysis. This was a retrospective, case-controlled study. All patients who underwent hemodialysis using a tunneled central catheter (TCC) from January 1, 2006 to October 8, 2008 were examined. Eleven patients who received ALT were compared with 15 case control subjects. The effectiveness of ALT for prevention of CRB was determined by the incidence of CRBs during the study period and catheter removal secondary to a CRB. A total of 10,961 catheter-days were calculated from 47 TCCs among 26 patients. The two groups had similar demographics and risk factors for CRBs. There were a total of 17 incidences of CRBs with a rate of 1.55 incidences/1,000 catheter-days. The rate of CRB was significantly lower in the ALT group (0.69 incidences/1,000 catheter-days) than the control group (2.54 incidences/1,000 catheter-days), p=0.041. The rate of catheters removal due to a CRB was also significantly less in the ALT group (0.5 catheter removed/1,000 catheter-days) than the control group (2.41 catheter removed/1,000 catheter-days), p=0.041. Seven out of 9 patients died in the control group secondary to CRBs. Three patients died in the ALT group; however none of these deaths were associated with CRB. Our study results revealed that ALT is an effective way to prevent catheter related bacteremia among veterans with central venous catheter for chronic hemodialysis.

Effectiveness of the antibiotic lock therapy for the treatment of port-related enterococci, Gram-negative, or Gram-positive bacilli bloodstream infections

Objective The purpose of this study is to evaluate the efficacy of antibiotic lock therapy to treat port-related enterococci, Gram-negative, or Gram-positive bacilli bloodstream infections. Patients and Methods We conducted a prospective observational study including all patients with port-related bacteremia diagnosed at the Clinica Universitaria de Navarra, Pamplona, Spain. During a 36-month period, 110 patients were diagnosed with port-related bacteremia. Of these patients, 18 met criteria to be enrolled in the study. They were treated with a combination of systemic and antibiotic lock therapy (12–24 h/day during 7–14 days). Treatment effectiveness was assessed by clinical and microbiologic criteria. Results Treatment was associated with clinical and microbiologic success in 88.8% of our patients (2/2 of the Propionibacterium acnes, 5/5 of the Corynebacterium spp., 6/7 of the Gram-negative bacillus, and 3/4 of the Enterococcus faecium port-related bloodstream infections). Mean increase of port life span for all patients after bacteremia was 288 days (range, 0–1403 days). Conclusion Antibiotic lock therapy combined with systemic antibiotics appears to be a safe and effective treatment of port-related bacteremia caused by enterococci, Gram-negative, or Gram-positive bacilli if the patient is stable and no septic syndrome is associated.

Infecciones asociadas a los catéteres utilizados para la hemodiálisis y la diálisis peritoneal

Las infecciones asociadas a los catéteres utilizados tanto para hemodiálisis como para diálisis peritoneal (DP) constituyen una de las causas de morbimortalidad más importante en pacientes que precisan un tratamiento sustitutivo renal permanente. Staphylococcus aureus en pacientes en hemodiálisis y S. aureus y Pseudomonas aeruginosa en pacientes en DP son los microorganismos más frecuentemente aislados. Actualmente, no están establecidas las pruebas diagnósticas más rentables en infecciones de catéter en pacientes en hemodiálisis, por lo que se utilizan los empleados para las infecciones de los catéteres venosos centrales (CVC) en general. El tratamiento es similar al de otros CVC con algunas recomendaciones especiales. En pacientes en DP la peritonitis es una de las complicaciones más graves. La mejoría de las condiciones higiénicas en la inserción de los catéteres, el tratamiento de los portadores nasales de S. aureus , el tratamiento regular del orificio de salida de los catéteres y el sellado del catéter se han asociado con una disminución en las infecciones asociadas a catéter en pacientes en hemodiálisis y DP. Catheter-related infections in hemodialysis (HD) and peritoneal dialysis (PD) are one of the most common causes of morbidity and mortality in patients with end-stage renal disease. Staphylococcus aureus in HD patients and S. aureus and Pseudomonas aeruginosa in PD patients are the most common causative organisms isolated. Currently, the diagnostic tests with highest yield in suspected catheter-related infection in HD patients have not been established, and tests used for central venous catheters (CVC) in general are applied. Management of the infected HD catheter and the use of antimicrobial therapy are similar to the measures used for other CVCs, with some specific recommendations. Peritonitis is the most severe complication in PD patients. Improving hygiene conditions in catheter insertion, treatment of S. aureus nasal carriers, regular treatment of the catheter's exit site, and antibiotic lock therapy have been associated with a reduction of infectious episodes in HD and PD patients.

Infecciones asociadas a los catéteres utilizados para la hemodiálisis y la diálisis peritoneal

Catheter-related infections in hemodialysis (HD) and peritoneal dialysis (PD) are one of the most common causes of morbidity and mortality in patients with end-stage renal disease. Staphylococcus aureus in HD patients and S. aureus and Pseudomonas aeruginosa in PD patients are the most common causative organisms isolated. Currently, the diagnostic tests with highest yield in suspected catheter-related infection in HD patients have not been established, and tests used for central venous catheters (CVC) in general are applied. Management of the infected HD catheter and the use of antimicrobial therapy are similar to the measures used for other CVCs, with some specific recommendations. Peritonitis is the most severe complication in PD patients. Improving hygiene conditions in catheter insertion, treatment of S. aureus nasal carriers, regular treatment of the catheter's exit site, and antibiotic lock therapy have been associated with a reduction of infectious episodes in HD and PD patients.

New antibiotic agents for bloodstream infections

Infections due to multidrug-resistant pathogens have shown a dramatic worldwide increase in prevalence. Bloodstream infections (BSIs) represent an important cause of morbidity and mortality in hospitalised patients. Research in the field led to the introduction of several novel antibiotic agents in the fight against bacterial pathogens. New antibiotics used against Gram-positive bacteria, mainly meticillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, include daptomycin, linezolid, quinupristin/dalfopristin and semisynthetic lipoglycopeptides. Among the Gram-negative bacteria, extended-spectrum β-lactamase-producing Enterobacteriaceae as well as highly resistant Pseudomonas and Acinetobacter isolates are of particular concern. Doripenem is a recently approved carbapenem. Polymyxins are reconsidered as valuable therapeutic options for Gram-negative infections. Tigecycline, a glycylcycline, and ceftobiprole, a novel cephalosporin under investigation, have activity both against Gram-positive and Gram-negative organisms. In addition to the above agents, alternative treatment approaches that require further investigation have also been introduced into clinical practice. These include antibiotic lock therapy and continuous intravenous administration of antibiotics. In this article, we review the above treatment options for BSIs based on current clinical evidence. Comparative trials specifically focusing on patients with bacteraemia were generally not performed; however, a proportion of patients from the reported studies did have bacteraemia.

Infecciones asociadas a dispositivos intravasculares utilizados para la terapia de infusión

Catheter-related bloodstream infections are associated with recognized morbidity and mortality, especially in critically ill patients. Skin insertion site, the catheter hub, hematogenous seeding of the catheter tip from a distant site of infection, and infusate contamination are the sources of catheter colonization and infections. Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and Candida spp most commonly cause catheter-related bloodstream infection. Catheter-sparing diagnostic methods, such as differential quantitative blood cultures and time to positivity have emerged as reliable diagnostic techniques. Management of catheter-related infection varies according to the type of catheter involved. In most cases of nontunneled catheter-related bacteremia and fungemia, the catheter should be removed. For management of bacteremia and fungemia from a tunneled catheter or implantable device, such as a port, the decision to remove the catheter or device should be based on the severity of the patient's illness, documentation that the vascular-access device is infected, assessment of the specific pathogen involved, and presence of complications, such as endocarditis, septic thrombosis, tunnel infection, or metastatic seeding. When a catheter-related infection is documented and a specific pathogen is identified, systemic antimicrobial therapy should be narrowed and consideration given for antibiotic lock therapy, if the catheter or implantable device is not removed. Novel preventive strategies include cutaneous antisepsis, maximum sterile barrier, use of antimicrobial catheters, and antimicrobial catheter lock solution.

Antibiotic-lock therapy for long-term catheter-related bacteremia: a review of the current evidence

Catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality, especially among patients receiving hemodialysis, parenteral nutrition and chemotherapy. Antibiotic-lock therapy (ALT) represents a promising technique in the modern treatment of CRBSIs. In this review, we attempt to clarify the potential role of ALT in the treatment of long-term catheter-related bacteremia, based on the available evidence from published studies reporting on this issue. We identified 28 articles that were considered appropriate to be included in our review, only three of which were comparative studies. There is some evidence that ALT administered concurrently with systemic therapy may represent a significant therapeutic approach for CRBSIs involving long-term catheters. Prolonged infection-free catheter survival in the reported series is suggestive of sterilization of the catheters by ALT. The only reported comparison shows better outcome with ALT than with catheter exchange. Immunodeficient states, such as HIV, and the use of totally implanted devices instead of tunneled catheters may predispose to CRBSI treatment failure. No serious adverse effects, such as emergence of resistance or increased infectious complications, were found to be associated with the use of ALT in the reviewed studies. However, more comparative studies should be performed to examine this important therapeutic issue further.

Treatment of Dialysis Catheter–Related Staphylococcus aureus Bacteremia With an Antibiotic Lock: A Quality Improvement Report

Dialysis catheter-related bacteremia is often treated successfully by instilling an antibiotic-heparin solution into the catheter lumen (an antibiotic lock) in conjunction with systemic antibiotic therapy without removal of the catheter. The efficacy of this therapy is uncertain in Staphylococcus aureus bacteremia. Quality improvement report. 113 catheter-dependent hemodialysis outpatients with S aureus catheter-related bacteremia treated with a standardized antibiotic lock protocol. Data for all patients with catheter-related bacteremia are recorded in a prospective database. In conjunction with systemic antibiotic therapy (vancomycin for methicillin-resistant S aureus or cefazolin for methicillin-sensitive S aureus), an antibiotic lock was instilled into each catheter lumen after each dialysis session for 3 weeks. Treatment failure is defined as persistent fever after 48 hours of antibiotic therapy or recurrent S aureus bacteremia within 90 days. Clinical cure is defined as resolution of fever and no recurrence of bacteremia. Major infection-related complications within 6 months were documented. The catheter could not be salvaged in 67 patients (59%) because of persistent fever in 40 patients and recurrent bacteremia in 27 patients. A clinical cure was achieved in 46 patients (41%). A serious complication of catheter-related bacteremia occurred in 9.7% of all patients (11 of 113 patients). Serious complications were observed in 25% of patients (10 of 40 patients) with persistent fever, but only 1.4% of all other patients (1 of 73 patients; P < 0.0001). This was a single-center study. Serum antibiotic levels were not measured. Routine antibiotic lock therapy is not appropriate for patients with S aureus catheter-related bacteremia. Serious complications occur primarily in patients with persistent fever.

Antibiotic-lock therapy and erythromycin for treatment of catheter-related Candida parapsilosis and Staphylococcus aureus infections

1. Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 2006; 6: 629–40. 2. Archambault M, Petrov P, Hendriksen RS et al. Molecular characterization and occurrence of extended-spectrum beta-lactamase resistance genes among Salmonella enterica serovar Corvallis from Thailand, Bulgaria, and Denmark. Microb Drug Resist 2006; 12: 192–8. 3. Jacoby GA, Walsh KE, Mills DM et al. qnrB, another plasmidmediated gene for quinolone resistance. Antimicrob Agents Chemother 2006; 50: 1178–82. 4. Park CH, Robicsek A, Jacoby GA et al. Prevalence in the United States of aac(6’)Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother 2006; 50: 3953–5. 5. Peirano G, Agerso Y, Aarestrup FM et al. Occurrence of integrons and antimicrobial resistance genes among Salmonella enterica from Brazil. J Antimicrob Chemother 2006; 58: 305–9. 6. Aarestrup FM. International spread of multidrug-resistant Salmonella Schwarzengrund in food products. Emerg Infect Dis 2007; 13: 726–31.

Comparative Activities of Daptomycin, Linezolid, and Tigecycline against Catheter-Related Methicillin-Resistant Staphylococcus Bacteremic Isolates Embedded in Biofilm

In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4-hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent.

Treatment of long-term intravascular catheter-related bacteraemia with antibiotic-lock therapy

Bacteraemia is a major complication associated with the use of long-term intravascular catheters. Conservative treatment using antibiotic-lock therapy (ALT) has been shown to be useful in some studies, but the evidence supporting its impact in clinical care is still scarce. We evaluated the outcome of the episodes of catheter-related bacteraemia (CRB) associated with long-term intravascular devices used for chemotherapy or parenteral nutrition and that were managed with ALT during a 44 month period in our hospital. Episodes of CRB associated with catheters implanted in the same department during the same period, and that were managed with only systemic antibiotics were used as a control group. Antibiotic-lock solution consisted of a heparin solution of 20 IU/mL including vancomycin (for Gram-positive microorganisms) or ciprofloxacin or gentamicin (for Gram-negative bacilli), all at a concentration of 2 mg/mL. ALT was used for a minimum of 8-12 h/day, during 5-14 days. Effectiveness was assessed by clinical and microbiological criteria. A total of 801 long-term intravascular devices were placed in 105 patients during this period. There were 127 episodes of bacteraemia documented in these patients, with 92 being CRB. Of these, 48 episodes fulfilled inclusion criteria for the analysis. Nineteen episodes were treated with ALT plus systemic antibiotics, and 29 episodes were treated only with systemic antibiotics. Isolated microorganisms were similar in the two groups. The catheter had to be removed during therapy in one episode in the antibiotic-lock group and in seven episodes in the control group. Relapse of the bacteraemia with the same microorganism after stopping therapy was observed in two and three patients in the study group and the control group, respectively. Overall, successful treatment was achieved in 84% and 65% of the episodes in the antibiotic-lock group and the control group, respectively (P = 0.27). ALT appears as an effective conservative treatment in the management of CRB associated with long-term intravascular devices (84% in the present series), especially in infections caused by coagulase-negative staphylococci.

A simplified method of antibiotic lock therapy for Broviac–Hickman catheters using a CLC 2000 connector device

We report a simplified method of performing antibiotic lock therapy (ALT) based on a disposable central venous catheter (CVC) hub device, CLC 2000, enabling an open-ended CVC to be flushed with normal saline solution without heparin. ALT was administered through a CLC 2000 connector for recurrent CVC-bloodstream infections (BSI) by the same organism in four patients and for CVC colonization in five patients. The antibiotic concentration obtained in the lumen of the CVC with ALT was 2,500-fold higher than the minimum inhibiting concentration of targeted bacteria for patients treated with vancomycin, 2,500-80,000-fold higher for patients treated with teicoplanin, and 10,000-fold higher for the patient treated with amikacin. All CVC-BSIs treated with ALT resulted in complete clinical and microbiological responses. No case of malfunction in withdrawing or flushing the CVC and no precipitation during the administration of the antibiotic solution was observed. No recurrence of CVC-BSI or CVC colonization by the same organism was diagnosed during subsequent follow-up, despite the fact that all patients had further periods of severe neutropenia. At the last follow-up, three CVCs had been removed for other infections (fever of unknown origin in two; fungemia in one), four CVCs had been removed at the end of therapy, and one CVC is still in situ 20 months after ALT. In conclusion, a course of ALT is feasible in cancer patients with infected but much-needed CVCs before resorting to removal. The use of the CLC 2000 connector device simplifies the procedure for preparation and administration of ALT without compromising its efficacy.