Extracellular DNA released by glycine-auxotrophic Staphylococcus epidermidis small colony variant facilitates catheter-related infections.

Though a definitive link between small colony variants (SCVs) and implant-related staphylococcal infections has been well-established, the specific underlying mechanism remains an ill-explored field. The present study analyzes the role SCVs play in catheter infection by performing genomic and metabolic analyses, as well as analyzing biofilm formation and impacts of glycine on growth and peptidoglycan-linking rate, on a clinically typical Staphylococcus epidermidis case harboring stable SCV, normal counterpart (NC) and nonstable SCV. Our findings reveal that S. epidermidis stable SCV carries mutations involved in various metabolic processes. Metabolome analyses demonstrate that two biosynthetic pathways are apparently disturbed in SCV. One is glycine biosynthesis, which contributes to remarkable glycine shortage, and supplementation of glycine restores growth and peptidoglycan-linking rate of SCV. The other is overflow of pyruvic acid and acetyl-CoA, leading to excessive acetate. SCV demonstrates higher biofilm-forming ability due to rapid autolysis and subsequent eDNA release. Despite a remarkable decline in cell viability, SCV can facilitate in vitro biofilm formation and in vivo survival of NC when co-infected with its normal counterparts. This work illustrates an intriguing strategy utilized by a glycine-auxotrophic clinical S. epidermidis SCV isolate to facilitate biofilm-related infections, and casts a new light on the role of SCV in persistent infections.

Therapeutic implications of C. albicans-S. aureus mixed biofilm in a murine subcutaneous catheter model of polymicrobial infection.

Biofilm-associated polymicrobial infections tend to be challenging to treat. Candida albicans and Staphylococcus aureus are leading pathogens due to their ability to form biofilms on medical devices. However, the therapeutic implications of their interactions in a host is largely unexplored. In this study, we used a mouse subcutaneous catheter model for in vivo-grown polymicrobial biofilms to validate our in vitro findings on C. albicans-mediated enhanced S. aureus tolerance to vancomycin in vivo. Comparative assessment of S. aureus recovery from catheters with single- or mixed-species infection demonstrated failure of vancomycin against S. aureus in mice with co-infected catheters. To provide some mechanistic insights, RNA-seq analysis was performed on catheter biofilms to delineate transcriptional modulations during polymicrobial infections. C. albicans induced the activation of the S. aureus biofilm formation network via down-regulation of the lrg operon, repressor of autolysis, and up-regulation of the ica operon and production of polysaccharide intercellular adhesin (PIA), indicating an increase in eDNA production, and extracellular polysaccharide matrix, respectively. Interestingly, virulence factors important for disseminated infections, and superantigen-like proteins were down-regulated during mixed-species infection, whereas capsular polysaccharide genes were up-regulated, signifying a strategy favoring survival, persistence and host immune evasion. In vitro follow-up experiments using DNA enzymatic digestion, lrg operon mutant strains, and confocal scanning microscopy confirmed the role of C. albicans-mediated enhanced eDNA production in mixed-biofilms on S. aureus tolerance to vancomycin. Combined, these findings provide mechanistic insights into the therapeutic implications of interspecies interactions, underscoring the need for novel strategies to overcome limitations of current therapies.

Role of Venous Access Port Cultures in the Management of Port-Related Infections.

PURPOSE: To determine the impact of port and catheter tip cultures on the clinical management of port-related infections. MATERIALS AND METHODS: Patients whose ports were removed for infection between January 2016 and December 2019 were retrospectively identified. The study sample included 68 ports removed for suspected catheter-related bloodstream infection (CRBSI) and 27 ports removed for local infection. Port surface, catheter tip, and blood culture results were recorded. Antimicrobial therapy before and after port removal was recorded. The impact of culture results on port infection management was determined. RESULTS: Of the 68 ports removed from patients with CRBSI, 78% received empiric antibiotics. Of these patients, blood cultures led to a change in therapy in 77%. Catheter tip cultures were positive in 32% whereas port surface cultures were positive in 53% of patients. Culture results did not influence antimicrobial therapy in any patient with CRBSI. Of 27 port removals performed for local infection, catheter tip cultures were positive in 41% whereas port surface cultures were positive in 59% of patients. Port surface cultures led to a change in therapy in 33% of local infections. Port surface cultures were significantly more likely to impact management if removal was performed for local infection than for CRBSI (33% vs. 0%, respectively; P < .001). Port surface cultures were inclusive of all positive catheter tip cultures. CONCLUSIONS: For patients with suspected CRBSI, blood cultures alone are sufficient to guide therapy. Port cultures may be justified in the setting of local infection. Catheter tip cultures are unnecessary if port surface cultures are performed.

Lack of efficacy of echinocandins against high metabolic activity biofilms of Candida parapsilosis clinical isolates.

Candida parapsilosis produces biofilm, which colonizes catheters and other invasive medical devices that are manipulated by health care workers. In previous studies, C. parapsilosis in vitro biofilms have exhibited high resistance rates against conventional antifungals, but susceptibility to both echinocandins and lipid formulations of amphotericin B (lipid complex and liposomal). However, a recent study showed good activity of amphotericin B deoxycholate on the biomass of C. parapsilosis biofilms. Although moderate activity of echinocandins has been demonstrated against low metabolic activity biofilms of C. parapsilosis, few studies have analyzed the action of these drugs on high metabolic activity biofilms. Moreover, high biofilm-forming isolates have been associated with central venous catheter-related fungemia outbreaks and higher mortality rates. Therefore, it is relevant to verify the activity of the main antifungal drugs against high metabolic activity biofilms of C. parapsilosis. Our study aimed to evaluate the in vitro activity of amphotericin B deoxycholate, anidulafungin, caspofungin, and micafungin against high biofilm-forming and high metabolic activity clinical isolates of C. parapsilosis. Our results showed good activity of amphotericin B against C. parapsilosis biofilms, but none of the echinocandin drugs was effective. This suggests that amphotericin B deoxycholate may be a better choice than echinocandins for the treatment of biofilm-associated infections by C. parapsilosis, mainly in countries with insufficient health care resources to purchase lipid formulations of amphotericin B. These results warn of the possibility of persistent catheter-related candidemia caused by high biofilm-forming C. parapsilosis strains when treated with echinocandin drugs.

Clinical efficacy of teicoplanin in the treatment of bloodstream infection caused by methicillin-resistant coagulase-negative staphylococci.

Empirical combination therapy with ß-lactams and glycopeptides is recommended for patients with presumed staphylococcal bloodstream infection (BSI). While coagulase-negative staphylococci (CNS) remain susceptible to vancomycin, such isolates have become less susceptible to teicoplanin. The aim of this retrospective study was to evaluate the clinical efficacy of teicoplanin in the treatment of BSI caused by methicillin-resistant CNS according to teicoplanin susceptibility. Inclusion criteria were patients with intravascular-catheter related BSIs caused by methicillin-resistant CNS (positive for two or more specimens); teicoplanin therapy; and at least one of the signs or symptoms caused by BSI. Antimicrobial resistance was defined as minimum inhibitory concentration (MIC) ≥8 µg/mL. The primary efficacy endpoint was clinical success evaluated 2 weeks after the completion of teicoplanin therapy [test of cure (TOC)]. Resistant rate of CNS was 0% for vancomycin and 22.9% for teicoplanin, and geometric mean MICs were 1.31 µg/mL and 3.41 µg/mL, respectively (p < 0.001). The catheter was removed in all patients except one, and high early clinical response at 72 h after starting therapy was obtained irrespective of teicoplanin susceptibility. The clinical success rate at TOC was 60% in patients with BSIs caused by teicoplanin-resistant strains, while 90% in patients with BSIs caused by susceptible strains (p = 0.052). In multivariate analyses, teicoplanin resistance was significant factor for decreased clinical success at TOC (adjusted odds ratio 0.138, 95% confidence interval 0.020-0.961, p = 0.045). Because of the poor clinical efficacy of teicoplanin against teicoplanin-resistant CNS, combination therapy comprising vancomycin and ß-lactam antibiotics should be considered in presumed staphylococci BSI.

Taurolidine as adjuvant treatment of relapsing peritonitis in peritoneal dialysis patients. / Taurolidina como tratamiento adyuvante en casos de peritonitis recidivante en pacientes en diálisis peritoneal.

Relapsing peritonitis in peritoneal dialysis patients is one of the complications that jeopardizes the continuity of the technique. It is often associated with the formation of biofilm in the lumen of the catheter. To date, its removal remains the only recommended attitude. Due to its antimicrobial and antifungal properties, taurolidine has been previously used for the sealing of central line catheters and hemodialysis. Despite the good results obtained, there is no evidence available regarding its utility in peritoneal dialysis. This case report describes the use of taurolidine (TauroLock™HEP500) in 5 patients with relapsing peritonitis after antibiotic treatment completion. Mean follow-up for the detection of recurrences was 13.4 months. In 4 patients with infections caused by Staphylococcus epidermidis, eradication was achieved. In the remaining case, caused by Staphylococcus aureus, the taurolidine seal was ineffective and the removal of the catheter was required.

Antibiotic Susceptibility and Therapy in Central Line Infections in Pediatric Home Parenteral Nutrition Patients.

BACKGROUND: Patients receiving home parenteral nutrition (HPN) are at high-risk for central line-associated bloodstream infections (CLABSI). There are no published management guidelines, however, for the antibiotic treatment of suspected CLABSI in this population. Historical microbiology data may help inform empiric antimicrobial regimens in this population. OBJECTIVE: The aim of the study was to describe antimicrobial resistance patterns and determine the most appropriate empiric antibiotic therapy in HPN-dependent children experiencing a community-acquired CLABSI. METHODS: Single-center retrospective cohort study evaluating potential coverage of empiric antibiotic regimens in children on HPN who developed a community-acquired CLABSI. RESULTS: From October 1, 2011 to September 30, 2017, there were 309 CLABSI episodes among 90 HPN-dependent children with median age 3.8 years old.Fifty-nine percent of patients carried the diagnosis of surgical short bowel syndrome. Organisms isolated during these infections included 60% Gram-positive bacteria, 34% Gram-negative bacteria, and 6% fungi. Among all staphylococcal isolates, 51% were methicillin sensitive. Among enteric Gram-negative organisms, sensitivities were piperacillin-tazobactam 71%, cefepime 97%, and meropenem 99%. Organisms were sensitive to current institutional standard therapy with vancomycin and piperacillin-tazobactam in 69% of cases compared with vancomycin and cefepime or vancomycin an meropenem in 85% and 96% of cases (both P < 0.01). CONCLUSIONS: Empiric antimicrobial therapy for suspected CLABSI in HPN-dependent children should include therapy for methicillin-resistant staphylococci as well as enteric Gram-negative organisms. Future studies are needed to evaluate clinical outcomes based upon evidence-based antimicrobial regimens.

Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms.

Antifungal lock therapy has received significant interest in the last few years because the frequently usage of intravascular devices is associated with an increasing number of catheter-related bloodstream infections caused by Candida species. Antifungal combinations with synergistic interaction can be a good choice for antifungal lock therapy; therefore, interactions were examined between two echinocandins (caspofungin and micafungin) and the chitin synthesis inhibitor nikkomycin Z against Candida albicans and C. parapsilosis biofilms. Susceptibility was evaluated using the XTT-based checkerboard microdilution method, while the nature of interactions was assessed by calculating fractional inhibitory concentration indices and using the Bliss independence model. Mathematic-based evaluations were supplemented with fluorescent LIVE/DEAD viability assay. The results obtained by statistical interaction analyses correlated well with the viability assay. The tested echinocandins with nikkomycin Z caused an extended cell death and the structure of the biofilm was sparse compared to the control, especially for C. albicans. The findings support the simultaneous usage of nikkomycin Z and caspofungin or micafungin in alternative therapies such as the antifungal lock therapy. SIGNIFICANCE AND IMPACT OF THE STUDY: Antifungal lock therapy can be a potential therapeutic approach to eradicate the intraluminal Candida biofilms; however, there is no approved lock strategy against fungal species so far. The results of this study provide valuable evidence that nikkomycin Z acts synergistically in combination with caspofungin or micafungin against biofilms. In addition, this synergy was more pronounced for micafungin combined with nikkomycin Z. Therefore, nikkomycin Z can be considered as a potential agent in antifungal lock therapy especially with micafungin against C. albicans or C. parapsilosis biofilms.

Evaluation of the potential of colicins to prevent extraluminal contamination of urinary catheters by Escherichia coli.

The feasibility of using colicins to create an antimicrobial lubricant to prevent extraluminal catheter contamination during urinary catheter insertion was assessed. Levels of resistance of uropathogenic Escherichia coli to antibiotics and colicins were compared. The results showed that antibiotics and colicins possess similar frequencies of resistance to a single drug, whereas colicins exhibit significantly lower levels of multidrug resistance (22%) than antibiotics (42%). Colicins and antibiotics showed complementary inhibitory activity, with each targeting different subsets of pathogenic isolates. The collateral impact of these two antimicrobials on genera that are members of the fecal/vaginal/urinary microbiome was assessed, with colicins showing significantly less collateral damage than antibiotics. Using a novel colicin, SR4, minimum inhibitory concentrations (MICs) for a panel of 30 uropathogenic isolates were determined and showed that SR4 achieved the same antimicrobial efficacy as gentamicin using 20-30% less drug. An SR4-impregnated catheter lubricant was created and its ability to prevent extraluminal urinary catheter contamination in vitro was demonstrated. These data indicate that a colicin-impregnated lubricant may provide a viable prophylactic option for preventing catheter-associated urinary tract infections.

Gentamicin as Empirical Treatment in Hemodialysis Patients: Safety, Pharmacokinetics, and Pharmacodynamics.

The aim of this study was to describe the safety profile and pharmacokinetic/pharmacodynamic parameters in end-stage renal disease patients who received gentamicin as empirical treatment in catheter-related bacteremia when they showed infection signs, regardless of the timing of the next HD. Patients received gentamicin 3 mg/kg before blood culture extraction when they showed infection signs and regardless of the timing of next hemodialysis session. Serum concentrations were collected after the gentamicin administration (peak level) and before the next HD (trough level). Toxicities and adverse drug events were registered. The main pharmacokinetic/pharmacodynamic goal for Gram-negative infections was peak:minimum inhibitory concentration (MIC) ≥10. Sixteen patients were included. Nephrotoxicity was not assessed in this population, and no ototoxicity was found. According to microbial isolation and gentamicin susceptibility, the value of peak:MIC was 5.4 ± 2.0. The administration of gentamicin in these conditions was safe. Estimated pharmacokinetic values were consistent with previous studies and appropriate according to peak:MIC goal for Gram-negative organisms with MIC ≤1 mg/L.

Synergistic Antifungal Effect of Amphotericin B-Loaded Poly(Lactic-Co-Glycolic Acid) Nanoparticles and Ultrasound against Candida albicans Biofilms.

Candida albicans is a human opportunistic pathogen that causes superficial and life-threatening infections. An important reason for the failure of current antifungal drugs is related to biofilm formation, mostly associated with implanted medical devices. The present study investigated the synergistic antifungal efficacy of low-frequency and low-intensity ultrasound combined with amphotericin B (AmB)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (AmB-NPs) against C. albicans biofilms. AmB-NPs were prepared by a double-emulsion method and demonstrated lower toxicity than free AmB. We then established biofilms and treated them with ultrasound and AmB-NPs separately or jointly in vitro and in vivo The results demonstrated that the activity, biomass, and proteinase and phospholipase activities of biofilms were decreased significantly after the combination treatment of AmB-NPs with 42 kHz of ultrasound irradiation at an intensity of 0.30 W/cm2 for 15 min compared with the controls, with AmB alone, or with ultrasound treatment alone (P < 0.01). The morphology of the biofilms was altered remarkably after joint treatment based on confocal laser scanning microscopy (CLSM), especially in regard to reduced thickness and loosened structure. Furthermore, the same synergistic effects were found in a subcutaneous catheter biofilm rat model. The number of CFU from the catheter exhibited a significant reduction after joint treatment with AmB-NP and ultrasound for seven continuous days, and CLSM and scanning electron microscopy (SEM) images revealed that the biofilm on the catheter surface was substantially eliminated. This method may provide a new noninvasive, safe, and effective therapy for C. albicans biofilm infection.

Streptococcus mitis/oralis Causing Blood Stream Infections in Pediatric Patients.

Viridans streptococci are still under investigation concerning epidemiology, pathogenesis and clinical presentations. We aimed to investigate the clinical presentations and outcomes of pediatric patients infected with Streptococcus mitis/oralis. Based on the accumulation of bloodstream infections (BSI) caused by S. mitis/oralis in 4 patients in our Hematology and Bone Marrow Transplantation Department at a particular time, a review of the medical and microbiological records of pediatric patients with positive blood cultures for S. mitis/oralis in the entire hospital was performed. In addition, a retrospective case-control study was conducted. Pulsed-field gel electrophoresis of S. mitis/oralis in 4 patients displayed unrelatedness of the strains. A total of 53 BSI (42 BSI and 11 catheter-related BSI) were analyzed. Thirty-four percent of patients with BSI caused by S. mitis/oralis had febrile neutropenia. Clinical and microbiological outcomes were favorable and infection-related mortality was not observed. Although not significant, previous antibiotic use and trimethoprim-sulfamethoxazole prophylaxis were more common in the case group. S. mitis/oralis seems likely an important agent in bacteremic children who are particularly neutropenic because of the underlying hematologic and oncologic diseases. Prompt management of infections with appropriate antimicrobials, regarding antibiotic susceptibilities of organisms, may facilitate favorable outcomes.

Catheter-associated bacterial flora in patients with benign prostatic hyperplasia: shift in antimicrobial susceptibility pattern.

BACKGROUND: Men with urinary retention secondary to benign prostatic hyperplasia (BPH) are prone to genitourinary infections. Physicians should be aware of the current antimicrobial susceptibility pattern in this population if empirical treatment is needed. The goal of this study was to evaluate variations in prevalence, composition and antimicrobial susceptibility of bacterial flora in men with indwelling catheters subjected to surgery for BPH in chosen time periods since 1994. Necessary changes in empirical therapy were also assessed. METHODS: All patients with indwelling catheters admitted to a single urological center for BPH surgery in the years 1994-1996, 2004-2006, and 2011-2015 were considered. Catheterization times and results of urine cultures from samples collected at admission were evaluated. Susceptibility for selected antimicrobials was compared separately for Gram negative and Gram positive species. For each agent and for their combinations effectiveness of empirical therapy was calculated dividing the number of patients with bacteriuria susceptible to the agents by the total number of patients with bacteriuria. RESULTS: Bacteriuria was present in 70% of 169, 72% of 132, and 69% of 156 men in the respective time periods. The incidence of Gram-positive strains increased from 10 to 37% (P < 0.001). Their susceptibility to amoxicillin/clavulanate was fluctuating (81, 61, 77%; P=NS). No vancomycin-resistant strain was present. Gram-negative flora composition was stable. Their susceptibility decreased to ciprofloxacin (70 to 53%; P = 0.01) and amoxicillin/clavulanate (56 to 37%; P < 0.01) while it increased to gentamycin (64 to 88%; P < 0.001) and co-trimoxazole (14 to 62%; P < 0.001); susceptibility to amikacin remained high (> 85%). Only two cases of resistance to carbapenems in 2004-2006 were found. In vitro effectiveness of amikacin + amoxicillin/clavulanate in empirical therapy was slowly decreasing (87 to 77%; P=NS). Imipenem was found the most effective single agent (90-95%) and its efficacy was even improved by adding vancomycin (97-98%). CONCLUSIONS: Substantial rise in the incidence of Gram-positive species and fluctuations in antimicrobial susceptibility patterns were found. Empirical therapy of genitourinary infection in catheterized men with BPH should now involve antimicrobial agents effective both to Enterococci and Enterobacteriaceae. Periodic monitoring and publishing data on antimicrobial susceptibility for this population is necessary.

To Pull or Not to Pull: Salvaging Central Line Catheters in Home Parenteral Nutrition.

PURPOSE OF REVIEW: Catheter-related blood stream infections (CRBSI) pose a significant risk to patients on home parenteral nutrition (HPN). Recurrent loss of catheters can lead to scarring and eventual loss of central access, a potentially fatal situation for patients dependent on HPN. RECENT FINDINGS: In the past, the standard of care to treat these infections required catheter removal. More recently, several studies have indicated that many CRBSI can be treated without removal of the catheter. Successful treatment without removal can be achieved by intentionally following a catheter salvage protocol. We define this as a previously defined protocol to accurately diagnose CRBSI, identify the organism(s) involved, and effectively treat not only the blood stream infection, but also sterilize the catheter. For patients on HPN with CRBSI, consider attempting line salvage if the patient is not suffering from severe sepsis, other infection related complications, or certain specific infections. Success rates vary depending on the organism causing the infection and the risks; benefits and chance of success should be considered when deciding to attempt line salvage.

Non-Antibiotic Antimicrobial Catheter Lock Solutions in Patients on Home Parenteral Nutrition.

Patients on home parenteral nutrition (HPN) are dependent on central venous access for long-term sustenance, and catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality in this patient population. As such, there is much interest in finding new methods for preventing CRBSIs in patients on HPN. As it is thought that these infections are preceded by microbial colonization of the catheter, one approach is to use antimicrobial catheter lock solutions. Although antibiotic catheter lock solutions have been present for decades, their use has been mostly limited to the treatment of CRBSIs due to concern for promoting microbial resistance. Recently, however, with the advent of non-antibiotic antimicrobial catheter lock solutions, this approach is gaining popularity as a promising method to decrease rates of CRBSI in HPN patients.

[Inpatient candiduria: etiology, susceptibility to antifungal drugs and risk factors]. / Candiduria en pacientes hospitalizados: etiología, sensibilidad a los fármacos antifúngicos y factores de riesgo.

OBJECTIVE: Candida could become the second most frequent cause of nosocomial urinary tract infection. Although Candida albicans is the most important species, others have arisen as emerging pathogens. The aim of this study was to analyze the presence of candiduria in inpatients. METHODS: We performed a retrospective study of Candida isolates from adult inpatient urocultures over five years, gathering and tabulating data on: the species; susceptibility to fluconazole, amphotericin B, and voriconazole (Vitek2, BioMerieux); presence of catheter; hospital department of origin; and patient age and sex. RESULTS: We detected 289 yeast episodes, observing an annual increase: 134 (46.4%) were non-C. albicans yeasts, with 57 (19.7%) being Candida glabrata, 37 (12.8%) Candida tropicalis, 25 (8.6%) Candida parapsilosis, and 10 (3.5%) Candida lusitaniae. Most isolates derived from catheterized (240, 83.0%) and Internal Medicine Department (118, 40.8%) patients, observing an annual increase; 152 (52.6%) isolates were from males, and the mean age was >65 years. Susceptibility to antifungals was >85%. CONCLUSIONS: Inpatient urocultures should include data on the presence of Candida, which is more prevalent in Internal Medicine Department inpatients, in those with urinary catheter, and in over 65-year-olds. Almost half of the isolates were non-C. albicans yeasts, and we recommend complete identification of the species involved.

Bioluminescence imaging increases in vivo screening efficiency for antifungal activity against device-associated Candida albicans biofilms.

Fungal infections are a major problem for a growing number of mostly immunocompromised patients. Candida albicans is an important human fungal pathogen causing mucosal and deep tissue infections, of which the majority are associated with biofilm formation on medical implants. Animal models that are currently in use to test antifungal drugs are limited to ex vivo analyses, requiring host sacrifice that excludes longitudinal monitoring of dynamic processes during biofilm formation in the live host. As a solution, we introduce non-invasive, dynamic imaging and quantification of C. albicans biofilm formation in vivo and subsequent evaluation of treatment efficacy against these biofilms using bioluminescent C. albicans in a catheter-associated mouse model. Bioluminescence imaging (BLI) allowed us to evaluate baseline biofilm load before the start of therapy, which is necessary for correct evaluation and interpretation of antibiofilm efficacy in vivo. Moreover, we demonstrate that this BLI approach monitors the antibiofilm activity of different antifungal agents efficiently in vitro and in vivo. In this study, BLI revealed superior antibiofilm activity for echinocandins compared with amphotericin B and fluconazole. In vitro, anidulafungin showed the highest antibiofilm activity, followed by micafungin and caspofungin. In vivo, caspofungin significantly decreased the biofilm fungal load, as documented by the lower BLI signal and confirmed by CFU counts. In conclusion, this BLI approach increases the power and efficiency of screening and validation of antimycotics both under in vitro and in vivo conditions, thereby refining pre-clinical therapy studies.

No effect of vancomycin MIC ≥ 1.5 mg/L on treatment outcome in methicillin-susceptible Staphylococcus aureus bacteraemia.

The vancomycin minimum inhibitory concentration (MIC) has been shown to affect the outcome of methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. In this study, the outcomes of patients with MSSA bacteraemia with a vancomycin MIC ≥ 1.5 mg/L were assessed. A prospective cohort of patients with MSSA bacteraemia in two tertiary-care hospitals was collected. The vancomycin MIC was determined by Etest. Staphylococcus aureus strains were categorised as low (<1.5 mg/L) or high (≥1.5 mg/L) vancomycin MIC. First- and second-line treatments were recorded and classified as optimal, appropriate and inappropriate. The primary endpoint was 30-day mortality. A total of 250 patients with S. aureus bacteraemia were analysed, of whom 64 (25.6%) had strains with a high vancomycin MIC. History of dialysis (P = 0.001) and ultimately fatal disease (P = 0.005) were associated with strains with a high vancomycin MIC. The 30-day mortality was 24.7% (46/186) in patients with a low vancomycin MIC versus 28.1% (18/64) in patients with a high vancomycin MIC (P = 0.592) and did not differ significantly after adjustment for the appropriateness of the antibiotic treatment. Patients with a high vancomycin MIC were less frequently associated with complicated bacteraemia (15.6% vs. 39.2%; P = 0.001). In conclusion, vancomycin MIC ≥ 1.5 mg/L was not associated with 30-day mortality but was associated with uncomplicated bacteraemia in MSSA bacteraemia, regardless of the first- and second-line treatment.