Journal Club: Quarterly Roundup of Notable Articles (August 2025–November 2025)
Year: 2025
Type: article
Abstract: COMPARATIVE CLINICAL CHARACTERISTICS AND OUTCOMES OF CANDIDA (CANDIDOZYMA) AURIS VERSUS NON-CANDIDOZYMA AURIS CANDIDEMIA IN NONNEUTROPENIC PATIENTS IN SOUTH INDIA Methodology This large retrospective study[1] from a South Indian tertiary-care centre analyzed 372 candidemia episodes in 352 nonneutropenic adults, comparing clinical features, risk factors, beta-D-glucan (BDG) performance, antifungal susceptibilities, and outcomes between Candidozyma auris (22.8%) and non–C. auris infections. Candida tropicalis remained the most common species, whereas C. auris was the second-most frequent and increased notably during the COVID-19 years. C. auris cases were characterized by longer prior hospitalization (24 vs. 8 days), higher prior antifungal exposure (43.5% vs. 13.2%), and greater ECMO use (10.6% vs. 1.4%), consistent with a strongly nosocomial pattern. No C. auris episodes originated from the urinary tract. Antifungal susceptibility testing showed 100% fluconazole resistance and 81% amphotericin-B resistance in C. auris, but echinocandins remained susceptible. Across all species, fluconazole susceptibility was only 50.9%. BDG testing, which was available for 48 C. auris and 131 non-auris infections, showed unexpectedly frequent false negatives: 27% in C. auris and 22% in non-auris cases, including 22.7% of Candida albicans and 35.7% of Candida parapsilosis. Surveillance blood cultures were obtained in two-thirds of patients, and persistent candidemia occurred in about one third, strongly linked to long-standing central venous catheters. Candida endocarditis was identified in 4% of patients, mainly through transesophageal echocardiography (TEE), and almost always in those with persistent fungemia or prolonged intravascular line use. Overall, 28-day mortality was high (40.6%); although crude survival appeared slightly better in C. auris infections, species type was not an independent predictor of mortality. Instead, deaths were more closely linked to older age, higher SOFA scores, and candidemia arising from nonurinary sources. DISCUSSION This study emphasizes several important points for clinical practice and antifungal stewardship. First, the findings strongly support an echinocandin-first empiric approach for suspected candidemia without a clear urinary source, particularly in C. auris, which demonstrated 81% amphotericin resistance and universal fluconazole resistance. Second, the BDG results are surprising; almost one-quarter of candidemia cases were BDG-negative, including infections caused by typically high-BDG organisms such as C. albicans. This challenges the routine practice of using the high negative predictive value of BDG to discontinue antifungals. The study also found a 4% rate of Candida endocarditis, stressing the importance of doing TEE in anyone with persistent candidemia or high-risk indwelling devices. Importantly, C. auris itself was not an independent predictor of mortality, and poor outcomes were related more to host factors and illness severity (such as SOFA ≥5) than by species alone. There is also a need for consistently following candidemia care bundles. Together, these findings help guide empiric treatment choices, the limitations of BDG, and reinforce the need for strong infection control measures for limiting C. auris transmission in intensive care units. CLOXACILLIN VERSUS CEFAZOLIN FOR METICILLIN-SUSCEPTIBLE STAPHYLOCOCCUS AUREUS BACTERAEMIA: A PROSPECTIVE, OPEN-LABEL, MULTICENTER, NONINFERIORITY, RANDOMIZED CLINICAL TRIAL Methodology The cloxacillin versus cefazolin for meticillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa) trial[2] was a multicenter, open-label, randomized, noninferiority study comparing cefazolin with cloxacillin for the treatment of nonsevere methicillin-susceptible staphylococcus aureus (MSSA) bloodstream infections (BSIs). Adults were randomized after 48–120 h of appropriate therapy once they showed clinical improvement and had no exclusion criteria such as prosthetic valve endocarditis, central nervous system (CNS) involvement, retained intravascular devices, or uncontrolled deep foci. The primary endpoint was a strict day-90 composite including survival, relapse, microbiological clearance, and clinical cure, with a 12% noninferiority margin selected for clinical relevance. Outcomes were reviewed by independent blinded assessors to minimize bias. The trial also performed blaZ genotyping to study the effects of inoculum effect on cefazolin. Although the study enrolled fewer participants than planned, the results were consistent across all groups. DISCUSSION CloCeBa showed that cefazolin is noninferior to cloxacillin for nonsevere, source-controlled MSSA bloodstream infection, with almost identical rates of clinical cure, relapse-free survival, and microbiological success by day 90. Even with a strict composite endpoint, cefazolin performed just as well, and there was no signal of increased relapse or persistent bacteremia, including in patients infected with blaZ Type A strains, suggesting that while the inoculum effect is real in vitro, it did not translate into clinical failure in this population. While mortality was low and similar across both groups, the notable difference was significantly less acute kidney injury, fewer serious adverse events, and far fewer treatment discontinuations in the cefazolin group compared to cloxacillin. Since CloCeBa enrolled patients only after clinical improvement and excluded left-sided endocarditis, retained prosthetic material, deep uncontrolled abscesses, CNS involvement, and other high-inoculum states, its conclusions apply mainly to the majority of common MSSA BSIs, such as line-related or soft-tissue associated infections that clear quickly with early management. Within this large patient group, CloCeBa provides strong randomized clinical trial-level evidence that cefazolin can be considered the default first-line therapy. More complex infections remain outside the scope of the data, and many clinicians may still prefer an antistaphylococcal penicillin for deep or device-related disease. These findings were reinforced by early results from the SNAP platform trial,[3] which includes a far broader, real-world SAB population. SNAP also shows that cefazolin performs as well as flucloxacillin for 90-day outcomes and causes less nephrotoxicity, strengthening the safety argument. While SNAP does not address the inoculum effect, both trials point in the same direction: for the majority of MSSA bacteremia, especially catheter-related or soft-tissue associated infections that respond quickly, cefazolin is a safe, effective, and often preferable option. DALBAVANCIN FOR TREATMENT OF STAPHYLOCOCCUS AUREUS BACTEREMIA: THE DOTS RANDOMIZED CLINICAL TRIAL Methodology The dalbavancin as an option for treatment of staphylococcus aureus bacteremia (DOTS) trial was a multicentre, open-label, assessor-masked, randomized controlled study comparing two-dose dalbavancin regimen (1500 mg on days 1 and 8) to standard therapy as definitive consolidation therapy for S. aureus bacteremia (SAB). It included adults with complicated SAB (persistent bacteremia before clearance, deep-infection focus which had been drained with absence of hardware, intravascular catheter related with removal of device, and right-sided endocarditis), who had achieved documented blood-culture clearance and clinical stability following 3–10 days of standard IV β-lactam or glycopeptide therapy. It excluded high-risk populations, i.e. left-sided endocarditis, retained infected prosthetic material, CNS infection, uncontrolled deep foci, and severe immunocompromise. Randomization was 1:1 to dalbavancin versus continuation of standard IV therapy for a total planned duration of 4–8 weeks. The primary endpoint was the desirability of outcome ranking (DOOR) at day 70, which included clinical response, infectious and safety complications, mortality, and quality-of-life outcomes. Secondary endpoints included day-70 clinical efficacy and longer-term outcomes such as osteomyelitis recurrence at day 180. DISCUSSION The DOTS trial[4] demonstrated that although dalbavancin did not achieve superiority on the DOOR composite, its clinical efficacy was comparable to standard intravenous therapy, supporting its use as a consolidation option in patients who are stable and have cleared their bacteremia. A major practical advantage is the ability to complete treatment without prolonged central venous access, reducing catheter-related complications and simplifying OPAT requirements. The study did observe a numerically higher rate of osteomyelitis recurrence in the dalbavancin arm at longer follow-up, suggesting that deep or high-inoculum infections may require more sustained antimicrobial exposure than a two-dose regimen provides. Because DOTS excluded patients with left-sided endocarditis, retained hardware, CNS involvement, or uncontrolled deep foci, the results are most applicable to an intermediate-complexity group of SAB rather than the most severe or device-associated presentations. As noted in the accompanying editorial by Paul Sax,[5] the “negative” DOOR result does not diminish the clinically meaningful finding that dalbavancin performed similarly to standard therapy while avoiding the burdens of PICC lines, daily IV infusions, and OPAT logistics. Cost remains the primary barrier to wider adoption, but early system-level experiences suggest that reductions in line complications and earlier discharge may help offset these expenses. In this context, DOTS provides supportive evidence that dalbavancin is a feasible, patient-friendly alternative for selected SAB patients with controlled infection. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Author: Sujata Rege
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7118088889