Ruth Reitzel

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

ABSTRACT 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.

Utility of Galactomannan Enzyme Immunoassay and (1,3) β-d-Glucan in Diagnosis of Invasive Fungal Infections: Low Sensitivity for Aspergillus fumigatus Infection in Hematologic Malignancy Patients

ABSTRACT Previous studies have reported that galactomannan (GM) enzyme immunoassay and 1,3 beta-glucan (BG) assay may be useful diagnostic tools, but their sensitivities are variable. We compared the performances of both tests. Between October 2002 and May 2005, 82 patients were prospectively monitored for 12 weeks. A total of 414 samples were tested by GM assay and 409 samples were tested by BG assay for the following four groups of patients: those with invasive aspergillosis (IA), those with other mold infections (Fusarium, scedosporium, zygomycosis, etc.), those with candidemia, and control patients. Blood samples were obtained twice on week 1 and once every other week for a total of 12 weeks. Patients in the invasive fungal infection groups had comparable risk factors. The sensitivity of the GM test was significantly higher for patients with IA due to non-fumigatus Aspergillus species than for patients with IA due to Aspergillus fumigatus (49% versus 13%; P < 0.0001) or with other mold infections (49% versus 6%; P < 0.0001). However, the sensitivity range (47% to 64%) and specificity (88%) of the BG assay were comparable among all patients tested, regardless of the infecting pathogen. The performance of GM-based diagnosis appears to be better for detecting non-fumigatus Aspergillus species. The diagnostic marker BG was shown to have a higher sensitivity than that of GM in detecting IA and other mold infections in hematologic malignancy patients.

Novel Antiseptic Urinary Catheters for Prevention of Urinary Tract Infections: Correlation of In Vivo and In Vitro Test Results

ABSTRACT Urinary catheters are widely used for hospitalized patients and are often associated with high rates of urinary tract infection. We evaluated in vitro the antiadherence activity of a novel antiseptic Gendine-coated urinary catheter against several multidrug-resistant bacteria. Gendine-coated urinary catheters were compared to silver hydrogel-coated Foley catheters and uncoated catheters. Bacterial biofilm formation was assessed by quantitative culture and scanning electron microscopy. These data were further correlated to an in vivo rabbit model. We challenged 31 rabbits daily for 4 days by inoculating the urethral meatus with 1.0 × 109 CFU streptomycin-resistant Escherichia coli per day. In vitro, Gendine-coated urinary catheters reduced the CFU of all organisms tested for biofilm adherence compared with uncoated and silver hydrogel-coated catheters (P < 0.004). Scanning electron microscopy analysis showed that a thick biofilm overlaid the control catheter and the silver hydrogel-coated catheters but not the Gendine-coated urinary catheter. Similar results were found with the rabbit model. Bacteriuria was present in 60% of rabbits with uncoated catheters and 71% of those with silver hydrogel-coated catheters (P < 0.01) but not in those with Gendine-coated urinary catheters. No rabbits with Gendine-coated urinary catheters had invasive bladder infections. Histopathologic assessment revealed no differences in toxicity or staining. Gendine-coated urinary catheters were more efficacious in preventing catheter-associated colonization and urinary tract infections than were silver hydrogel-coated Foley catheters and uncoated catheters.

Anti-adherence activity and antimicrobial durability of anti-infective-coated catheters against multidrug-resistant bacteria

OBJECTIVES To investigate the anti-adherence and antimicrobial durability of anti-infective catheters against multidrug-resistant (MDR) Staphylococcus aureus (resistant to vancomycin, rifampicin and methicillin) and MDR Gram-negative bacteria (Stenotrophomonas maltophilia, Acinetobacter baumannii/calcoaceticus and Enterobacter agglomerans) that are often associated with catheter-related bloodstream infections (CRBSIs). METHODS Catheters impregnated with minocycline and rifampicin (M/R) or with silver-platinum and carbon (SPC) or with chlorhexidine and silver sulfadiazine (CHX/SS) were compared with non-coated catheters. Adherence of organisms was tested by using an established biofilm colonization model. All isolates were rifampicin-resistant. Antimicrobial durability was tested by soaking 1 cm segments of the catheter in serum and determining zones of inhibition against the tested organisms at weekly intervals. RESULTS The M/R catheters showed significantly superior anti-adherence activity and more prolonged antimicrobial durability when compared with CHX/SS-central venous catheter (CVC), SPC-CVC and uncoated control catheters against MDR and vancomycin-resistant S. aureus (MDR VRSA) (all P values < or = 0.02), MDR S. maltophilia (all P values < 0.005) and MDR A. baumannii/calcoaceticus (all P values < 0.002), respectively. M/R-CVC and CHX/SS-CVC had comparable anti-adherence and antimicrobial durability against MDR E. agglomerans, and these two were superior to SPC-CVC and the uncoated control catheters (all P values < 0.001). CONCLUSIONS M/R-CVC demonstrated superior anti-adherence activity and more prolonged antimicrobial durability when compared with other approved anti-infective catheters against MDR VRSA and/or MDR Gram-negative bacteria that are often associated with CRBSIs. This finding could explain their efficacy and better performance in clinical studies.

Clinical effectiveness and risk of emerging resistance associated with prolonged use of antibiotic-impregnated catheters: more than 0.5 million catheter days and 7 years of clinical experience.

Objectives:Catheters coated with minocycline and rifampin are proven to decrease the rates of central line-associated bloodstream infection; however, it is unclear whether success occurs independent of other infection control precautions. We evaluated the effect of catheters coated with minocycline and rifampin with and without other infection control precautions on our rates of central line-associated bloodstream infection in critically ill patients and on antibiotic resistance throughout the hospital and in the intensive care unit. Design:Retrospective clinical cohort study conducted during 1999–2006 with an observational laboratory component. Setting:A tertiary university-based cancer center. Patients:All 8009 patients admitted to the medical intensive care unit were subjects for the surveillance of central line-associated bloodstream infection. All Staphylococcus aureus and coagulase-negative staphylococci clinical isolates cultured at our institution during the same period were subjects for laboratory testing. Interventions:Using catheters coated with minocycline and rifampin and implementing infection control precautions. Measurements and Main Results:Incidence of central line-associated bloodstream infection in the medical intensive care unit. Change in resistance to tetracycline and rifampin in clinically relevant staphylococcal isolates in the intensive care unit and hospitalwide. During the study period, 9200 catheters coated with minocycline and rifampin were used hospitalwide over a total of 511,520 catheter days. The incidence of central line-associated bloodstream infection per 1000 patient days in the medical intensive care unit significantly and gradually decreased from 8.3 in 1998 to 1.2 in 2006 (p ≤ .001). The resistance of S. aureus and coagulase negative staphylococci clinical isolates to tetracycline or rifampin in the intensive care unit and on a hospitalwide level remained stable or decreased significantly during the same period. Conclusions:Catheters coated with minocycline and rifampin significantly decreased the incidence of central line-associated bloodstream infection in the medical intensive care unit in a manner that was independent and complementary to the infection control precautions. Although this study strongly suggests an association between catheters coated with minocycline and rifampin use and a decrease in central line-associated bloodstream infection, because of multiple other concurrent interventions, the results should be interpreted cautiously until a prospective study is conducted. Furthermore, long-term use of these devices is not associated with increased resistance of staphylococcal isolates to tetracycline and rifampin in the intensive care unit or throughout the hospital.

Improved antibiotic-impregnated catheters with extended-spectrum activity against resistant bacteria and fungi.

ABSTRACT Minocycline-rifampin-impregnated central venous catheters (M/R CVCs) have been shown to be efficacious in reducing catheter-related bloodstream infections (CRBSI) and inhibiting the biofilm adherence of resistant Gram-positive and Gram-negative pathogens, with the exception of Pseudomonas aeruginosa and Candida spp. To expand the spectrum of antimicrobial activity, a novel second-generation M/R catheter was developed by adding chlorhexidine (CHX-M/R). CVCs and peripherally inserted central catheters (PICCs) were impregnated with CHX-M/R and compared with first-generation M/R catheters, CHX-silver sulfadiazine-treated CVCs (CHX/SS-CVCs), chlorhexidine-treated PICCs, and uncoated catheters. A biofilm catheter colonization model was used to assess the efficacy of catheters against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), P. aeruginosa, Candida albicans, and Candida glabrata. CHX-M/R-impregnated CVCs were the only antimicrobial catheters that completely inhibited the biofilm colonization of all resistant bacterial and fungal organisms tested at all time intervals, and they were significantly superior to uncoated catheters (all P values were ≤0.003). Furthermore, CHX-M/R-coated CVCs had a significantly more effective and prolonged (up to 3 weeks) antimicrobial activity against MRSA and P. aeruginosa than M/R, CHX/SS, and uncoated CVCs (P < 0.0001). Similarly, CHX-M/R-coated PICCs were also superior to M/R-coated and CHX-coated PICCs in preventing biofilms of MRSA, VRE, P. aeruginosa, and Candida species (P value = 0.003 for all). Our study shows that novel CHX-M/R-coated catheters have unique properties in completely inhibiting biofilm colonization of MRSA, VRE, P. aeruginosa, and fungi in a manner superior to that of M/R- and chlorhexidine-treated catheters.

Comparative In Vitro Efficacies and Antimicrobial Durabilities of Novel Antimicrobial Central Venous Catheters

ABSTRACT We investigated the efficacies and durability of novel antimicrobial central venous catheters (CVCs) in preventing the adherence of microbial organisms to the surfaces of the CVCs. Novel antimicrobial CVCs investigated in this in vitro study were impregnated with antibiotics (minocycline and rifampin), with Oligon agent (silver, platinum, and carbon black), with approved antiseptics (chlorhexidine and silver sulfadiazine), or with a novel antiseptic agent, gendine, which contains gentian violet and chlorhexidine. When tested against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, gendine-coated CVC segments provided protection against bacterial adherence significantly more than all other types of tested CVCs (P < 0.05). Gendine-coated CVCs also provided better protection against Candida albicans and Candida parapsilosis than CVCs impregnated with antibiotics or with silver, platinum, and carbon (P < 0.02). After 28 days of being soaked in serum, the CVCs impregnated with chlorhexidine and silver sulfadiazine and the CVCs impregnated with silver, platinum, and carbon had lost antimicrobial activity against MRSA, P. aeruginosa, and C. parapsilosis, and the CVCs impregnated with minocycline and rifampin had lost activity against P. aeruginosa and C. parapsilosis. The CVCs impregnated with gendine maintained antimicrobial activities against MRSA, P. aeruginosa, and C. parapsilosis after 28 days of being soaked in serum. Central venous catheters impregnated with the novel investigational antiseptic gendine showed in vitro efficacy and provided protection against bacterial adherence more than other approved novel antimicrobial-coated CVCs.

The prevention of biofilm colonization by multidrug-resistant pathogens that cause ventilator-associated pneumonia with antimicrobial-coated endotracheal tubes

Ventilator-associated pneumonia (VAP) continues to be the nosocomial infection associated with the highest mortality in critically ill patients. Since silver-coated endotracheal tubes (ETT) was shown in a multicenter prospective randomized trials to decrease the risk of VAP, we compared the efficacy of two antiseptic agents such as gardine- and gendine-coated ETTs with that of silver-coated ETTs in preventing biofilm. The ETTs were tested for their ability to prevent the biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter cloacae, and Candida albicans. Scanning electron microscopy studies revealed a heavy biofilm on uncoated and silver-coated ETT but not on the gardine-coated ETT. The gardine and gendine ETTs completely inhibited the formation of biofilms by all organisms tested and were more effective in preventing biofilm growth than the silver ETTs (p < 0.001). The gardine- and gendine-coated ETTs were more durable against MRSA than either the silver-coated or uncoated ETTs for up to 2 weeks (p < 0.0001). We have therefore shown that gardine- and gendine-coated ETTs are superior to silver-coated ETTs in preventing biofilm. Future animal and clinical studies are warranted to determine whether the gardine- and gendine-coated ETTs can significantly reduce the risk of VAP.

Glyceryl Trinitrate Complements Citrate and Ethanol in a Novel Antimicrobial Catheter Lock Solution To Eradicate Biofilm Organisms

ABSTRACT Antimicrobial catheter lock therapy is practiced to prevent lumenal-sourced infections of central venous catheters. Citrate has been used clinically as an anticoagulant in heparin-free catheter locks. Ethanol has also been widely studied as an antimicrobial lock solution component. This study reports on the synergy of glyceryl trinitrate (GTN) with citrate and ethanol in rapidly eradicating methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans biofilms in an in vitro model for catheter biofilm colonization. GTN has a long history of intravenous use as a hypotensive agent. It is potentially attractive as a component of a catheter lock solution because its physiologic half-life is quite short and its metabolic pathways are known. A lock containing 7% citrate and 20% ethanol required 0.01% GTN to fully eradicate biofilms of all test organisms within 2 h in the model. This GTN concentration is below the levels where clinically significant hypotensive effects are expected.

Multidrug-resistant Escherichia coli bacteremia in cancer patients

BACKGROUND Multidrug-resistant (MDR) Escherichia coli is a serious threat to cancer patients. We aimed to determine the risk factors associated with the development of MDR E coli bacteremia in cancer patients and the possibility of horizontal transmission. METHODS We conducted a 1:2 case-control study of 58 patients with MDR E coli bacteremia. The patients demographics, clinical characteristics, and antibiotic use were obtained. MDR E coli was defined as resistant strains to quinolones plus 1 of the following: piperacillin, ceftazidime, or cefepime. Repetitive sequence-based polymerase chain reaction (Rep-PCR) was used to identify DNA interstrain similarities. RESULTS Conditional multiple logistic analysis showed that admission to the hospital within the 30 days prior to infection and chemotherapy use were risk factors for infection with MDR E coli. Rep-PCR showed that, among the MDR E coli strains recovered, 48.6% showed >95% similarity, representing a possible clonal outbreak. Infection control measures were implemented and controlled this horizontal transmission. CONCLUSION Prior admission to the hospital and previous chemotherapy were independent risk factors of acquiring MDR E coli. Molecular fingerprinting techniques detected a possible nosocomial clonal outbreak of MDR E coli, which was aborted through infection control measures.