The effect of the COVID-19 pandemic on the incidence and resistance of Gram-negative bacilli and antimicrobial consumption in the intensive care units of a referral hospital in Buenos Aires.

BACKGROUND: There was a reported increase in the antimicrobial consumption in hospitals during the COVID-19 pandemic, accompanied by an increase in infections due to multidrug-resistant (MDR) bacteria. METHODS: This retrospective time series study from intensive care units in Buenos Aires examined changes in antibiotic consumption (defined daily doses/1000 patients/day), the incidence of Gram-negative bacilli (GNB) and the mechanism of resistance. Antibiotics were categorised into group 1 (agents against MDR GNB) and group 2 (agents against non-MDR infections). Bacteriological samples included respiratory samples and blood cultures. Periods were divided into pre-pandemic (July 2019 to March 2020) and pandemic (April 2020 to March 2022). Correlation coefficients (r) were analysed and the Mann-Whitney test was performed to compare both periods. RESULTS: During the study period, GNB incidence, group 1 antibiotic consumption and resistance mechanisms increased, whereas antibiotics decreased in group 2. A significant positive correlation was seen between the consumption of antibiotics in group 1 and the incidence of GNB (r = 0.63; P < 0.001) and resistance (r = 0.52; P = 0.002). Significant differences were found between pre-pandemic and pandemic periods regarding the medians of group 1 consumption (520 [408-570] vs. 753 [495-851] DDD/1000 patients/day; P = 0.029), incidence of GNB (12 [10-13] vs. 43 [25-52.5] cases/month; P < 0.001) and resistance mechanisms (5 [4-8] vs. 17 [10-25] cases/month; P < 0.001), extended-spectrum beta lactamases (2 [1-2] vs. 6 [3-8] cases/month; P < 0.001) and metallo-beta-lactamases (0 [0-0] vs. 6 [1.75-8.5] cases/month; P < 0.001). CONCLUSION: During the COVID-19 pandemic, the rise in GNB incidence and the amount of resistance mechanisms significantly correlated with the increase in consumption of agents against MDR strains.

Usefulness of Sona Aspergillus Galactomannan LFA with digital readout as diagnostic and as screening tool of COVID-19 associated pulmonary aspergillosis in critically ill patients. Data from a multicenter prospective study performed in Argentina.

COVID-19-associated pulmonary aspergillosis (CAPA) incidence varies depending on the country. Serum galactomannan quantification is a promising diagnostic tool since samples are easy to obtain with low biosafety issues. A multicenter prospective study was performed to evaluate the CAPA incidence in Argentina and to assess the performance of the lateral flow assay with digital readout (Sona Aspergillus LFA) as a CAPA diagnostic and screening tool. The correlation between the values obtained with Sona Aspergillus LFA and Platelia® EIA was evaluated. In total, 578 serum samples were obtained from 185 critically ill COVID patients. CAPA screening was done weekly starting from the first week of ICU stay. Probable CAPA incidence in critically ill patients was 10.27% (19/185 patients when LFA was used as mycological criteria) and 9% (9/100 patients when EIA was used as mycological criteria). We found a very good correlation between the two evaluated galactomannan quantification methods (overall agreement of 92.16% with a Kappa statistic value of 0.721). CAPA diagnosis (>0.5 readouts in LFA) were done during the first week of ICU stay in 94.7% of the probable CAPA patients. The overall mortality was 36.21%. CAPA patients' mortality and length of ICU stay were not statistically different from for COVID (non-CAPA) patients (42.11 vs 33.13% and 29 vs 24 days, respectively). These indicators were lower than in other reports. LFA-IMMY with digital readout is a reliable tool for early diagnosis of CAPA using serum samples in critically ill COVID patients. It has a good agreement with Platelia® EIA. LAY SUMMARY: The incidence of COVID-associated pulmonary aspergillosis (CAPA) in critically-ill Argentinian patients was established (10.27%). Serum galactomannan quantification was useful as a screening tool for this mycosis. A good agreement between Platelia® EIA and Sona Aspergillus LFA is reported.

Correlation of Etest and Neo-Sensitabs diffusion assays on Mueller-Hinton-methylene blue agar with broth microdilution reference method (CLSI-M27-A2) for testing susceptibilities of Cryptococcus neoformans to amphotericin B and fluconazole.

Cryptococcus neoformans causes disseminated infection in 7-8% of HIV positive patients admitted to Hospital F. J. Muñiz in Buenos Aires. Meningoencephalitis is the most frequent clinical manifestation and is one of the main causes of death in those patients with AIDS. The standard treatment for this mycosis consists of amphotericin B followed by fluconazole until two successive cultures of CFS are negative. Although resistance to these drugs is infrequent, minimal inhibitory concentrations (MIC) of some antifungals can be high. Since it is important to know the susceptibility levels of this fungus to the antifungal drugs usually employed in our institution, we analyzed the susceptibility test results of C. neoformans with two diffusion methods (Etest and NeoSensitabs tablets) employing Mueller-Hinton agar with 2% glucose and 0.5 microg/ml methylene blue. These results were compared with MICs obtained through the use of the broth microdilution reference method (CLSI). Results showed good agreement with the reference method, with no very major errors and only two major errors for fluconazole using NeoSensitabs tablets. For all the above mentioned, we confirm the usefulness of Mueller-Hinton agar to evaluate C. neoformans susceptibility to amphotericin B and fluconazole with these two agar diffusion methods.

Fluconazole and amphotericin B susceptibility testing of Cryptococcus neoformans: Results of minimal inhibitory concentrations against 265 isolates from HIV-positive patients before and after two or more months of antifungal therapy

La frecuencia de la criptococosis en los pacientes con sida sigue siendo alta en Argentina, a pesar de contar con terapia antirretroviral de alta eficacia. Sin tratamiento, esta micosis es habitualmente fatal.En la última década, el esquema terapéutico empleado para la criptococosis en el Hospital de Infecciosas “F. J. Muñiz” ha consistido en la administración de anfotericina B (AMB) seguida por fluconazol (FCZ), ya que la 5-fluorocitosina no se comercializa en Argentina. En un número considerable de pacientes no se negativizan los cultivos en 2–3 semanas de iniciada la terapia antifúngica, tal como sería deseable, y es posible aislar Cryptococcus neoformans en diferentes muestras clínicas aún después de dos ó más meses de tratamiento, inclusive en casos que mejoran clínicamente.El objetivo de este estudio fue evaluar el perfil de sensibilidad de aislamientos de C. neoformans obtenidos de 116 pacientes a las dos drogas mencionadas y compararlos con los de 149 aislamientos de los mismos enfermos después de, al menos, dos meses de tratamiento.Pudimos comprobar que la concentración inhibitoria mínima (CIM) de AMB fue⩽1μg/ml para los 265 aislamientos antes y después del tratamiento.La CIM de FCZ antes de iniciada la terapia fue ⩽8μg/ml en todos los casos. Solamente un aislamiento de un enfermo que presentó una recidiva mostró resistencia in vitro a esta droga (CIM⩾64μg/ml), y otros cuatro mostraron sensibilidad dosis dependiente (CIM 16–32μg/ml): tres de ellos de pacientes con recidivas y el cuarto de un enfermo que continuó con cultivos positivos durante largo tiempo. Estos valores no tuvieron correlación con la evolución de la micosis, como ya ha sido señalado en otras publicaciones(AU9

Cryptococcosis, a fatal disease without appropriate treatment, is still one of the major opportunistic mycoses in AIDS patients in Argentina despite the availability of high active anti-retroviral therapy (HAART).Over the last decade, drugs employed in the treatment of disseminated cryptococcosis at Infectious Diseases Hospital “F.J. Muñiz” included amphotericin B (AMB) followed by fluconazole (FCZ), due to the fact that flucytosine was not available in Argentina during this period. A considerable number of patients did not negativize cultures after 2–3 weeks of treatment as it was expected, and in some of them the isolation of Cryptococcus neoformans in different samples was still possible after 2 or more months of adequate therapy and even in cases with clinical improvement.The aim of this study was to establish the susceptibility profile of C. neoformans clinical isolates to those antifungals and to investigate whether there were any changes after at least 2 months of treatment. A total of 265 strains were studied (116 obtained from patients at diagnosis and 149 corresponding to the same individuals 2 months or more after receiving therapy). Susceptibility patterns before treatment to AMB showed MICs ≤1μg/ml for all the strains, and no increase was seen after treatment.All the strains were susceptible to FCZ (MIC≤8μg/ml) at diagnosis; but in a group with relapses or those who did not negativize cultures, one isolate became resistant after therapy (MIC≥64μg/ml) and other four showed dose-dependent susceptibility (MIC 16–32μg/ml). There was no relation between these results and clinical outcome as it was pointed out in other publications(AU)

Fluconazole and amphotericin B susceptibility testing of Cryptococcus neoformans: results of minimal inhibitory concentrations against 265 isolates from HIV-positive patients before and after two or more months of antifungal therapy.

Cryptococcosis, a fatal disease without appropriate treatment, is still one of the major opportunistic mycoses in AIDS patients in Argentina despite the availability of high active anti-retroviral therapy (HAART). Over the last decade, drugs employed in the treatment of disseminated cryptococcosis at Infectious Diseases Hospital "F.J. Muñiz" included amphotericin B (AMB) followed by fluconazole (FCZ), due to the fact that flucytosine was not available in Argentina during this period. A considerable number of patients did not negativize cultures after 2-3 weeks of treatment as it was expected, and in some of them the isolation of Cryptococcus neoformans in different samples was still possible after 2 or more months of adequate therapy and even in cases with clinical improvement. The aim of this study was to establish the susceptibility profile of C. neoformans clinical isolates to those antifungals and to investigate whether there were any changes after at least 2 months of treatment. A total of 265 strains were studied (116 obtained from patients at diagnosis and 149 corresponding to the same individuals 2 months or more after receiving therapy). Susceptibility patterns before treatment to AMB showed MICs < or =1 microg/ml for all the strains, and no increase was seen after treatment. All the strains were susceptible to FCZ (MIC< or =8 microg/ml) at diagnosis; but in a group with relapses or those who did not negativize cultures, one isolate became resistant after therapy (MIC> or =64 microg/ml) and other four showed dose-dependent susceptibility (MIC 16-32 microg/ml). There was no relation between these results and clinical outcome as it was pointed out in other publications.