Browsing by Author "Munita, José M."
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- ItemA Multicenter Study To Evaluate Ceftaroline Breakpoints : Performance in an Area with High Prevalence of Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Lineage(2019) Khan, Ayesha; Rivas, Lina M.; Spencer, María; Martínez, Rodrigo; Lam, Marusella; Rojas, Pamela; Porte, Lorena; Silva, Francisco; Braun, Stephanie; García Cañete, Patricia; Valdivieso, Francisca; Mvlhauser, Margareta; Lafourcade, Mónica; Miller, William R.; Arias, César A.; Munita, José M.
- ItemA multispecies outbreak of carbapenem-resistant bacteria harboring the blaKPC gene in a non-classical transposon element(2021) Wozniak Banchero, Aniela; Figueroa, Cristian; Moya-Flores, Francisco; Guggiana, Piero; Castillo, Claudia; Rivas Jiménez, Lina María; Munita, José M.; García Cañete, PatriciaAbstract Background Klebsiella pneumoniae is the most frequent KPC-producing bacteria. The blaKPC gene is frequently embedded in Tn4401 transposon, and less frequently in non-Tn4401 elements (NTEKPC) variants I-III. The first case of KPC in the UC-CHRISTUS Clinical Hospital was detected in Pseudomonas aeruginosa. Soon after this event, KPC was detected in 2 additional Pseudomonas aeruginosa, 3 Escherichia coli, 3 Enterobacter cloacae, 3 Klebsiella pneumoniae, and 1 Citrobacter freundii, isolated from 6 different patients. We aimed to elucidate the possible mechanisms of genetic transfer and dissemination of the blaKPC gene among isolates of this multispecies outbreak. A molecular epidemiology analysis of the above mentioned clinical isolates (n = 13) through Multi-Locus Sequence Typing, plasmid analysis, Pulsed-Field Gel-Electrophoresis, and Whole-genome sequencing (WGS) was performed. Results High-risk sequence types were found: K. pneumoniae ST11, P. aeruginosa ST654, and E. cloacae ST114. All enterobacterial isolates were not clonal except for 3 E. coli isolated from the same patient. WGS analysis in 6 enterobacterial isolates showed that 4 of them had blaKPC embedded in a novel variant of NTEKPC designated NTEKPC-IIe. Upstream of blaKPC gene there was a 570 pb truncated blaTEM-1 gene followed by an insertion sequence that was 84% similar to ISEc63, a 4473 bp element of the Tn3 family. Downstream the blaKPC gene there was a truncated ISKpn6 gene, and the inverted repeat right sequence of Tn4401. The ISec63-like element together with the blaKPC gene plus Tn4401 remnants were inserted in the Tra operon involved in conjugative transfer of the plasmid. This NTE was carried in a broad host-range IncN plasmid. P. aeruginosa isolates carried blaKPC gene embedded in a typical Tn4401b transposon in a different plasmid, suggesting that there was no plasmid transfer between Enterobacteriaceae and P. aeruginosa as initially hypothesized. Conclusions Most enterobacterial isolates had blaKPC embedded in the same NTEKPC-IIe element, suggesting that this multispecies KPC outbreak was due to horizontal gene transfer rather than clonal spread. This poses a greater challenge to infection control measures often directed against containment of clonal spread.
- ItemExcess burden of antibiotic-resistant bloodstream infections: evidence from a multicentre retrospective cohort study in Chile, 2018–2022(2024) Allel, Kasim; Peters, Anne; Haghparast-Bidgoli, Hassan; Spencer-Sandino, Maria; Conejeros Pavez, José Daniel Hernán; García Cañete, Patricia; Pouwels, Koen B.; Yakob, Laith; Munita, José M.; Undurraga, Eduardo A.Background: Antibiotic-resistant bloodstream infections (ARB BSI) cause an enormous disease and economic burden. We assessed the impact of ARB BSI caused by high- and critical-priority pathogens in hospitalised Chilean patients compared to BSI caused by susceptible bacteria. Methods: We conducted a retrospective cohort study from 2018 to 2022 in three Chilean hospitals and measured the association of ARB BSI with in-hospital mortality, length of hospitalisation (LOS), and intensive care unit (ICU) admission. We focused on BSI caused by Acinetobacter baumannii, Enterobacterales, Staphylococcus aureus, Enterococcus species, and Pseudomonas aeruginosa. We addressed confounding using propensity scores, inverse probability weighting, and multivariate regressions. We stratified by community- and hospital-acquired BSI and assessed total hospital and productivity costs. Findings: We studied 1218 adult patients experiencing 1349 BSI episodes, with 47.3% attributed to ARB. Predominant pathogens were Staphylococcus aureus (33% Methicillin-resistant ‘MRSA’), Enterobacterales (50% Carbapenem-resistant ‘CRE’), and Pseudomonas aeruginosa (65% Carbapenem-resistant ‘CRPA’). Approximately 80% of BSI were hospital-acquired. ARB was associated with extended LOS (incidence risk ratio IRR = 1.14, 95% CI = 1.05–1.24), increased ICU admissions (odds ratio OR = 1.25; 1.07–1.46), and higher mortality (OR = 1.42, 1.20–1.68) following index blood culture across all BSI episodes. In-hospital mortality risk, adjusted for time-varying and fixed confounders, was 1.35-fold higher (1.16–1.58) for ARB patients, with higher hazard ratios for hospital-acquired MRSA and CRE at 1.37 and 1.48, respectively. Using a societal perspective and a 5% discount rate, we estimated excess costs for ARB at $12,600 per patient, with an estimated annual excess burden of 2270 disability-adjusted life years (DALYs) and $9.6 (5.0–16.4) million. Interpretation: It is urgent to develop and implement interventions to reduce the burden of ARB BSIs, particularly from MRSA and CRE. Funding: Agencia Nacional de Investigación y Desarrollo ANID, Chile.
- ItemGeographic divergence of methicillin-resistant Staphylococcus aureus ST5-SCCmecI in the aftermath of a major earthquake and tsunami: impact of a plasmid harboring heavy metal resistance genes(2025) Martínez, José R. W.; Alcalde-Rico, Manuel; Jara-Videla, Estefanía; Reyes, Jinnethe; Carvajal, Lina P.; Sandra Rincon; Ríos, Rafael; Diaz, Lorena; Quesille-Villalobos, Ana; Riquelme-Neira, Roberto; Rivas, Lina; Moustafa, Ahmed M.; Blake, Hanson; Undurraga, Eduardo A.; Olivares-Pacheco, Jorge; García Cañete, Patricia; Araos, Rafael; Planet, Paul J.; Arias, César A.; Munita, José M.Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health menace. The global spread of MRSA is characterized by successive waves of epidemic clones dominating specific geographical regions. The acquisition of genes encoding resistance to heavy metals (HMRGs) is thought to be a key feature in the geographic divergence of MRSA. However, the cause-effect relationship between the presence of HMRGs and the divergence of MRSA clones remains to be clarified. In this study, we assessed the role that HMRGs may have played in the evolutionary divergence of the MRSA ST5-SCCmecI lineage in Latin America. We conducted a genomic characterization of 113 MRSA clinical isolates from six Latin American healthcare centers, including 53 isolates collected from two cities in Chile (Santiago and Concepción). We found a plasmid (pSCL4752) harboring arsenic, cadmium, and mercury resistance genes in 65% (n = 71) of the ST5-SCCmecI isolates. We also observed a geographic divergence associated with the presence of pSCL4752 in Chilean isolates, with a higher frequency in isolates from Concepción (88%) compared to Santiago (29%). Interestingly, a molecular clock analysis revealed that this divergence occurred in the aftermath of an 8.8 Mw earthquake and tsunami that struck the Concepción area in 2010. Moreover, our results demonstrate that the carriage of pSCL4752 can be beneficial or detrimental for ST5-SCCmecI isolates, depending on the environmental availability of these heavy metals. Our results suggest that the divergence of the ST5-SCCmecI MRSA lineage in Latin America could have been fostered by environmental disasters and influenced by the presence/absence of HMRGs harbored in a plasmi.
- ItemHeavy Metal Pollution From a Major Earthquake and Tsunami in Chile Is Associated With Geographic Divergence of Clinical Isolates of Methicillin-Resistant Staphylococcus aureus in Latin AmericaMartínez, José R.W.; Alcalde-Rico, Manuel; Jara-Videla, Estefanía; Ríos, Rafael; Moustafa, Ahmed M.; Blake, Hanson; Rivas, Lina; Carvajal, Lina P.; Rincon, Sandra; Díaz, Lorena; Jinnethe Reyes, Jinnethe; Quesille-Villalobos, Ana; Riquelme-Neira, Roberto; Undurraga, Eduardo A.; Olivares-Pacheco, Jorge; García Cañeta, Patricia del Carmen; Araos, Rafael; Planet, Paul J.; Arias, César A.; Munita, José M.Methicillin-resistant Staphylococcus aureus (MRSA) is a priority pathogen listed by the World Health Organization. The global spread of MRSA is characterized by successive waves of epidemic clones that predominate in specific geographical regions. The acquisition of genes encoding resistance to heavy-metals is thought to be a key feature in the divergence and geographical spread of MRSA. Increasing evidence suggests that extreme natural events, such as earthquakes and tsunamis, could release heavy-metals into the environment. However, the impact of environmental exposition to heavy-metals on the divergence and spread of MRSA clones has been insufficiently explored. We assess the association between a major earthquake and tsunami in an industrialized port in southern Chile and MRSA clone divergence in Latin America. We performed a phylogenomic reconstruction of 113 MRSA clinical isolates from seven Latin American healthcare centers, including 25 isolates collected in a geographic area affected by an earthquake and tsunami that led to high levels of heavy-metal environmental contamination. We found a divergence event strongly associated with the presence of a plasmid harboring heavy-metal resistance genes in the isolates obtained in the area where the earthquake and tsunami occurred. Moreover, clinical isolates carrying this plasmid showed increased tolerance to mercury, arsenic, and cadmium. We also observed a physiological burden in the plasmid-carrying isolates in absence of heavy-metals. Our results are the first evidence that suggests that heavy-metal contamination, in the aftermath of an environmental disaster, appears to be a key evolutionary event for the spread and dissemination of MRSA in Latin America.
- ItemImpact of inappropriate empirical antibiotic therapy on in-hospital mortality: a retrospective multicentre cohort study of patients with bloodstream infections in Chile, 2018–2022(2024) Allel, Kasim; Peters, Anne; Furuya-Kanamori, Luis; Spencer-Sandino, Maria; Pitchforth, Emma; Yakob, Laith; Munita, José M.; Undurraga, Eduardo A.Introduction: Empirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital mortality and the associated burden on BSI patients in Chile. Methods: We used a retrospective multicentre cohort study of BSI cases in three Chilean tertiary hospitals (2018–2022) to assess the impact of IEAT on 30-day and overall in-hospital mortality and quantify excess disease and economic burdens associated with IEAT. We determined the appropriateness of pathogen-antimicrobial pairings based on in vitro susceptibilities and pathogen-corresponding antibiotic treatment, allowing a 48-hour window after the initial blood culture. We addressed confounding using propensity scores and inverse probability weights (IPW). We used IPW-weighted logistic competing-risk survival models, including time-varying independent variables after blood tests as controls. Results: Among 1323 BSI episodes, 432 (33%) received IEAT, with an average time to adequate therapy of 4.6 days. Compared with adequate treatment, IEAT was associated with 30-day and overall mortality risks that were 1.31 and 1.24 times higher, respectively. These risks were further inflated between twofold and fourfold when antibiotic-resistant bacteria (ARB) was included. Competing-risk models showed associations between IEAT and IEAT-ARB combinations with in-hospital mortality. Accounting for time-varying variables yielded similar results. The economic burden of IEAT resulted in an additional cost of ~US$9900 from premature mortality and 0.46 disability-adjusted life-years per patient with BSI. Conclusión: Approximately one in three patients received IEAT, often associated with ARB. IEAT was linked to increased mortality risk and higher economic costs. Timely appropriate treatment, early pathogen detection and resistance profiling are likely to improve health and financial outcomes at the population level.
- ItemReal-World Performance of Susceptibility Testing for Ceftolozane/Tazobactam against Non-Carbapenemase- Producing Carbapenem-Resistant Pseudomonas aeruginosa(2022) Rivas, Lina; Martinez, José R.W.; Munita, José M.; Alcalde-Rico, Manuel; Olivares Pacheco, Jorge; García Cañete, Patricia; Olivares-Pacheco J.; Moreno, María Victoria; Rojas, Pamela; Wozniak Banchero, Aniela; Miller, William; Arias, Cesar A.; Khan, AyeshaCeftolozane/tazbactam (C/T) is a potent anti-pseudomonal agent that has clinical utility against infections caused by non-carbapenemase, producing-carbapenemresistant Pseudomonas aeruginosa (non-CP-CR-PA). Accurate, precise, and reliable antimicrobial susceptibility testing (AST) is crucial to guide clinical decisions. However, studies assessing the performance of different AST methods against non-CP-CR-PA (the main clinical niche for C/T), are lacking. Here, we evaluated performance of gradient strips (Etest and MIC test strip [MTS], and disk diffusion [DD]) using CLSI breakpoints. Additionally, we assessed the performance of DD using EUCAST breakpoints. For all susceptibility tests, we used a collection of 97 non-CP-CR-PA clinical isolates recovered from 11 Chilean hospitals. Both gradient strips and DD had acceptable performance when using CLSI breakpoints, yielding a categorical agreement (CA) of .90% and 92%, respectively. In contrast, DD using EUCAST breakpoints performed suboptimally (CA 81%). MTS yielded a higher essential agreement (EA, .90%) than Etest (84%). Importantly, the performance of all methods varied significantly when the isolates were stratified by their degree of susceptibility to other anti-pseudomonal b-lactams. All methods had 100% CA when testing isolates that were pan-susceptible to all b-lactams (Pan-β-S). However, the CA markedly decreased when testing isolates resistant to all b-lactams (Pan-β-R). Indeed, the CA was 81% for Etest (six errors), 78% for MTS (seven errors), and 78% and 56% for DD when using CLSI (seven errors) or EUCAST breakpoints (14 errors), respectively. Our results suggest that all manual AST methods have strikingly decreased performance in the context of Pan-β-R P. aeruginosa with potentially major clinical implications.