Resistance to fosfomycin is increasing and is significantly associated with extended-spectrum ß-lactamase-production in urinary isolates of Escherichia coli.

Fosfomycin has become a therapeutic option in urinary tract infections. Our objective was to evaluate the in vitro activity of fosfomycin against Escherichia coli isolated from urine samples in 2013, 2018 and 2021. We also determined a putative association between fosfomycin resistance and extended-spectrum ß-lactamases (ESBL) production. Fosfomycin activity was evaluated against 7367, 8128 and 5072 Escherichia coli urinary isolates in 2013, 2018 and 2021, respectively. We compare the prevalence of fosfomycin-resistant strains among the ESBL- and non-ESBL-producing isolates. MICs of fosfomycin, cefotaxime, and cefotaxime-clavulanate were determined by a microdilution method. 302 ESBL-producers were selected to determine MICs of fosfomycin by agar dilution and genes encoding ESBLs were detected by PCR. Among the total of ESBL-producing strains, 14.3%, 20.8% and 20% were resistant to fosfomycin in 2013, 2018 and 2021, respectively, whereas fosfomycin resistance in non-ESBL producers was 3.5%, 4.05% and 5.53% for each year (P ≤ 0.001). In the 302 selected ESBL-producing isolates, CTX-M was the main ESBL (228 isolates), being 50.7% CTX-M-15. Resistance to fosfomycin among these ESBL-producing strains was associated (P = 0.049) with isolates that produced the CTX-M type. Our data show that fosfomycin resistance is increasing in Escherichia coli urinary isolates and it is related to ESBL-production. A follow-up of fosfomycin resistance is required.

Plazomicin Activity against 346 Extended-Spectrum-ß-Lactamase/AmpC-Producing Escherichia coli Urinary Isolates in Relation to Aminoglycoside-Modifying Enzymes.

The activity of plazomicin and clinically relevant aminoglycosides was tested against 346 extended-spectrum-ß-lactamase/AmpC-producing Escherichia coli urinary isolates, and the results were correlated with the presence of aminoglycoside-modifying enzymes (AMEs). Data showed that plazomicin was very active against all ESBL/AmpC-producing E. coli urinary isolates. Its activity was not related to the AME genes studied.

Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?

Nosocomial pathogens can be associated with a variety of infections, particularly in intensive care units (ICUs) and in immunocompromised patients. Usually these pathogens are resistant to multiple drugs and pose therapeutic challenges. Among these organisms, Acinetobacter baumannii is one of the most frequent being encountered in the clinical setting. Carbapenems are very useful to treat infections caused by these drug-resistant Gram-negative bacilli, but carbapenem resistance is increasing globally. Combination therapy is frequently given empirically for hospital-acquired infections in critically ill patients and is usually composed of an adequate beta-lactam and an aminoglycoside. The purpose of this study was to evaluate the in vitro activity of plazomicin against carbapenem-resistant Acinetobacter baumannii. Amikacin was used as a comparator. The activity of plazomicin in combination with several different antibiotics was tested by disk diffusion, the checkerboard method, and time-kill studies. Synergy was consistently observed with carbapenems (meropenem and/or imipenem) along with plazomicin or amikacin. When the aminoglycosides were combined with other classes of antibiotics, synergy was observed in some cases, depending on the strain and the antibiotic combination; importantly, there was no antagonism observed in any case. These findings indicate the potential utility of plazomicin in combination with other antibiotics (mainly carbapenems) for the treatment of A. baumannii infections, including those caused by carbapenem-resistant isolates.

Evolution of antibody titers after two doses of mRNA Pfizer-BioNTech vaccine and effect of the third dose in nursing home residents.

OBJECTIVES: We evaluated the IgG antibody titer against SARS-CoV-2 in 196 residents of a Spanish nursing home after the second dose of the BNT162b2 vaccine and the evolution of this titer over time. The role of the third dose of the vaccine on immune-response is also analysed in 115 of participants. METHODS: Vaccine response was evaluated 1, 3 and 6 months after second dose of Pfizer-BioNTech COVID-19 Vaccine and 30 days after booster vaccination. Total anti-RBD (receptor binding domain) IgG immunoglobulins were measured to assess response. Six month after the second dose of vaccine and previously to the booster, T-cell response was also measured in 24 resident with different antibody levels. T-spot Discovery SARS-CoV-2 kit was used to identify cellular immunogenicity. RESULTS: As high as 99% of residents demonstrated a positive serological response after second dose. Only two patients showed no serologic response, two men without records of previous SARS-CoV-2 infection. A higher immune response was associated with prior SARS-CoV-2 infection regardless of the gender or age. The anti-S IgG titers decreased significantly in almost all the participants (98.5%) after six months of vaccination whatever previous COVID-infection. The third dose of vaccine increased antibody titers in all patients, although initial vaccination values were not restored in the majority of cases. CONCLUSION: The main conclusion of the study is that vaccine resulted in good immunogenicity in this vulnerable population. Nevertheless more data are needed on the long-term maintenance of antibody response after booster vaccination.

Adult T-cell leukemia/lymphoma in HTLV-1 non-endemic regions.

BACKGROUND: HTLV-1 infection is a neglected disease, despite producing neurological and lymphoproliferative severe illnesses and affect over 10 million people worldwide. Roughly 5% of HTLV-1 carriers develop Adult T-cell leukemia/lymphoma (ATLL), one of the most aggressive hematological malignancies. METHODS: A national HTLV-1 register exists since 1989 in Spain, a non-endemic country with a large migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic. The main features of all patients diagnosed with ATLL in Spain up to date are reported. RESULTS: A total of 451 cases of HTLV-1 infection had been reported in Spain until the end of year 2022. ATLL had been diagnosed in 35 (7.8%). The current average incidence of ATLL in Spain is of two cases per year. Women represent 57% of ATLL patients. Mean age at diagnosis was 47 years-old. Roughly 57% were Latin Americans and 26% Africans. At diagnosis, the majority presented with acute or lymphoma clinical forms. Survival was shorter than one year in most of them. Mean HTLV-1 proviral load was significantly greater in ATLL patients than in asymptomatic HTLV-1 carriers (2,305 vs 104 copies/104 PBMC). HTLV-1 subtyping in 6 ATLL patients found the 1a transcontinental variant (n = 4) and the Japanese variant (n = 2). All ATLL patients were negative for HIV-1, did not develop HTLV-1-associated myelopathy and were not transplant recipients. CONCLUSION: The rate of ATLL is very low in Spain and mostly associated to migrants from HTLV-1 endemic regions. Given the poor clinical outcome of ATLL, HTLV-1 testing should be performed at least once in all migrants coming from HTLV-1 endemic countries and in natives who have lived in or had sex partners from such regions.

In vitro activity of tedizolid (TR-700) against linezolid-resistant staphylococci.

OBJECTIVES: To compare the activity of tedizolid (formally known as torezolid and TR-700) with that of 15 agents against a collection of linezolid-resistant staphylococci (164 coagulase-negative staphylococci and 5 Staphylococcus aureus). METHODS: Antimicrobial susceptibility tests were performed using the broth microdilution method following the recommendations of the CLSI. RESULTS: All isolates were susceptible to vancomycin and tigecycline. Based on the MIC(90) values, the potency of tedizolid against coagulase-negative staphylococci was >16-fold greater than that of linezolid. Tedizolid retained activity against most of the linezolid-resistant staphylococci tested, including multidrug-resistant isolates with elevated linezolid MICs (32 to >128 mg/L). Of the isolates, 79.2% and 31.4% were inhibited by tedizolid at ≤ 4 mg/L and ≤ 2 mg/L, respectively. CONCLUSIONS: The results of this study confirm the activity of tedizolid against linezolid-resistant staphylococci. This new oxazolidinone could have an important role as a potential therapeutic agent against multidrug-resistant staphylococci.

Rapid identification of clinical isolates of Bacteroides species by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry.

The objective of this study was to compare MALDI-TOF MS and Rapid ID 32A with 16S rRNA gene sequencing, the reference method for identification of Bacteroides species. Results show that MALDI-TOF MS can be a good option for identification of Bacteroides species, especially if the database is expanded.

Comparison of performance of MALDI-TOF MS and MLST for biotyping carbapenemase-producing Klebsiella pneumoniae sequence types ST11 and ST101 isolates.

INTRODUCTION: The rapid identification and detection of carbapenemase-producing Klebsiella pneumoniae (CPKP) isolates is crucial to ascertain outbreaks, as well as to limit their spread. The current reference method for this purpose is multilocus sequence typing (MLST), which is laborious and expensive. Consequently, alternative typing methods are gaining attention, such as Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS). METHODS: This study sought to analyze MALDI-TOF MS as a typing method using 44 CPKP isolates that were well characterized by MLST. The most common types of samples from which these pathogens were isolated were skin and soft tissues (32%) and urine (29%). Half of the CPKP isolates were from hospitalized patients. Two approaches were followed for the analysis of the mass peak data obtained by MALDI-TOF MS. The first using all peaks obtained and the second using a selection of 21 characteristic peaks. RESULTS: The selection of 21 characteristic peaks showed greater discrimination power for ST11 and ST101. Principal component analysis (PCA) indicated that this dataset could be efficiently grouped with lineal classifiers. A Support Vector Machine (SVM) was chosen for this purpose after checking its capacity to classify bacterial strains on the basis of MALDI-TOF MS information. CONCLUSION: SVM was able to discriminate between ST11 and ST101 with high accuracy. In conclusion, our results reveal MALDI-TOF MS as a promising alternative technique for typing of CPKP isolates.

Clonal spread of levofloxacin-resistant streptococcus pneumoniae invasive isolates in Madrid, Spain, 2007 to 2009.

Among 1,349 Streptococcus pneumoniae invasive isolates, 45 (3.3%) were levofloxacin resistant. Serotype distribution was as follows: 8 (n=32 isolates), 19A (n=4 isolates), 7F (n=3 isolates), 9V (n=2 isolates), 10A (n=1 isolate), 19F (n=1 isolate), 6B (n=1 isolate), and nontypeable (n=1 isolate). Levofloxacin-resistant isolates had dual mutations in the gyrA and parC genes. Serotype 8 strains corresponded to a capsular switching of the Sweden(15A)-25 clone. Levofloxacin resistance was also detected among multiresistant (ST276(19A), Spain9V-ST156, ST88(19F), and ST1542(6B)) and among usually antibiotic-susceptible (Netherlands7F-ST191, ST1201(19A), and ST2639(10A)) clones.

Identification of CRF66_BF, a New HIV-1 Circulating Recombinant Form of South American Origin.

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17 gag , integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF "family" clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF.

Identification of CRF89_BF, a new member of an HIV-1 circulating BF intersubtype recombinant form family widely spread in South America.

Circulating recombinant forms (CRFs) contribute substantially to the HIV-1 pandemic. Among 105 CRFs described in the literature, 16 are BF intersubtype recombinants, most of South American origin, of which CRF12_BF is the most widely spread. A BF recombinant cluster identified in Bolivia was suggested to represent a new CRF_BF. Here we find that it belongs to a larger cluster incorporating 39 viruses collected in 7 countries from 3 continents, 22 of them in Spain, most from Bolivian or Peruvian individuals, and 12 in South America (Bolivia, Argentina, and Peru). This BF cluster comprises three major subclusters, two associated with Bolivian and one with Peruvian individuals. Near full-length genome sequence analyses of nine viruses, collected in Spain, Bolivia, and Peru, revealed coincident BF mosaic structures, with 13 breakpoints, 6 and 7 of which coincided with CRF12_BF and CRF17_BF, respectively. In a phylogenetic tree, they grouped in a clade closely related to these CRFs, and more distantly to CRF38_BF and CRF44_BF, all circulating in South America. These results allowed to identify a new HIV-1 CRF, designated CRF89_BF. Through phylodynamic analyses, CRF89_BF emergence was estimated in Bolivia around 1986. CRF89_BF is the fifth CRF member of the HIV-1 recombinant family related to CRF12_BF.

Comparative activities of TR-700 (torezolid) against staphylococcal blood isolates collected in Spain.

The in vitro activity of TR-700 (torezolid) was evaluated against a collection of 660 staphylococcal blood isolates. TR-700 showed excellent activity against all the staphylococci tested. The MIC(50) and MIC(90) values of TR-700, linezolid, daptomycin, and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) isolates were 0.25 and 0.5, 2 and 4, 0.5 and 0.5, and 1 and 2 microg/ml, respectively. TR-700 demonstrated greater in vitro potency than linezolid against staphylococci, including linezolid-resistant and vancomycin-nonsusceptible strains, and was 32-fold more active than linezolid against the seven cfr-positive MRSA strains tested.

Direct serogrouping of Streptococcus pneumoniae strains in clinical samples by use of a latex agglutination test.

Pneumotest-Latex (Statens Seruminstitut) was evaluated for direct serogrouping of Streptococcus pneumoniae strains in clinical samples from patients with invasive disease. The technique was accurate to its level of discrimination for 62 of 67 clinical samples (92.5%). Pneumotest-Latex would be a useful alternative for direct serogrouping of pneumococci in clinical samples.

[Comparative activity of daptomycin against clinical isolates of methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci]. / Actividad comparativa de la daptomicina frente a Staphylococcus aureus resistente a meticilina y frente a estafilococos coagulasa negativa.

INTRODUCTION: The objective of this study was to determine the in vitro activity of daptomycin and other agents against methicillin-resistant Staphylococcus aureus (MRSA) isolates from several sources and coagulase-negative staphylococci (CoNS) from clinically significant blood cultures. METHODS: We tested a total of 1186 staphylococci isolates (755 MRSA and 431 CoNS) collected as part of a multicenter surveillance program for antimicrobial resistance (VIRA study) from 40 medical centers throughout Spain between 2001 and 2006. Broth microdilution tests were performed according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: Most MRSA isolates were resistant to ciprofloxacin (96%) and erythromycin (79.7%). Daptomycin yielded a MIC(50)/MIC(90) of 0.5/1microg/mL in MRSA, compared with 1/2microg/mL for linezolid, vancomycin, and teicoplanin. Daptomycin MICs were in the range of < or =0.125-2microg/mL. Only 1 MRSA strain had a reproducible daptomycin MIC of 2microg/mL. Among CoNS isolates, the MIC range for daptomycin was < or =0.125-1microg/mL. Daptomycin was equally active against oxacillin-susceptible and oxacillin-resistant strains. CONCLUSION: Daptomycin was highly active against the staphylococci isolates studied. The activity of this agent was not affected by resistance to other antibiotics such as oxacillin, teicoplanin, linezolid, ciprofloxacin, or gentamicin. These data suggest that daptomycin may be useful for the treatment of severe infection caused by MRSA or CoNS.

Increase of serotype 8, ST53 clone, as the prevalent strain of Streptococcus pneumoniae causing invasive disease in Madrid, Spain (2012-2015).

INTRODUCTION: In recent years, Streptococcus pneumoniae serotype 8 has become the most prevalent cause of invasive pneumococcal disease (IPD) in Madrid, Spain. The objective of this study was to characterize the invasive clones of S. pneumoniae serotype 8 in Madrid over the 2012-2015 period. METHODS: From January 2012 to December 2015, a total of 1543 invasive isolates were studied. Serotyping was carried out by Pneumotest-Latex agglutination and Quellung reaction. Susceptibilities to penicillin, erythromycin and levofloxacin were determined by the Etest®. All serotype 8 strains were typed by multilocus sequence typing (MLST) and by pulsed-field gel electrophoresis (PFGE). RESULTS: Two hundred and forty-eight (248) serotype 8 strains were detected (16.1%) and 243 of them were available for molecular typing. Nine sequence types (STs) by MLST (8-ST53, 8-ST63, 8-ST404, 8-ST1107, 8-ST989, 8-ST1110, 8-ST2231, 8-ST3544 and 8-ST4301), and nine PFGE profiles were identified (one corresponding to each ST). The 8-ST53 clone was the most widespread, and increased from 53.8% among all serotype 8 isolates in 2012, to 90.1% in 2015. In contrast, the 8-ST63 clone, resistant to levofloxacin and erythromycin, decreased from 30.8%, among all serotype 8 strains in 2012, to 5.0% in 2015. CONCLUSIONS: The increase in our region of S. pneumoniae serotype 8, not included in conjugated vaccines, occurred at the expense of the 8-ST53 clone. On the contrary, the 8-ST63 clone decreased. Since clone 8-ST63 has the theoretical advantage of its levofloxacin-erythromycin resistance in comparison to 8-ST53, the predominance of 8-ST53 over 8-ST63 is striking.

Synergy of Linezolid with Several Antimicrobial Agents against Linezolid-Methicillin-Resistant Staphylococcal Strains.

Linezolid is a synthetic oxazolydinone active against multi-resistant Gram-positive cocci that inhibits proteins synthesis by interacting with the 50S ribosomal subunit. Although linezolid-resistant strains are infrequent, several outbreaks have been recently described, associated with prolonged treatment with the antibiotic. As an alternative to monotherapy, the combination of different antibiotics is a commonly used option to prevent the selection of resistant strains. In this work, we evaluated combinations of linezolid with classic and new aminoglycosides (amikacin, gentamicin and plazomicin), carbapenems (doripenem, imipenem and meropenem) and fosfomycin on several linezolid- and methicillin-resistant strains of Staphylococcus aureus and S. epidermidis, isolated in a hospital intensive care unit in Madrid, Spain. Using checkerboard and time-kill assays, interesting synergistic effects were encountered for the combination of linezolid with imipenem in all the staphylococcal strains, and for linezolid-doripenem in S.epidermidis isolates. The combination of plazomicin seemed to also have a good synergistic or partially synergistic activity against most of the isolates. None of the combinations assayed showed an antagonistic effect.

Comparison of performance of MALDI-TOF MS and MLST for biotyping carbapenemase-producing Klebsiella pneumoniae sequence types ST11 and ST101 isolates.

INTRODUCTION: The rapid identification and detection of carbapenemase-producing Klebsiella pneumoniae (CPKP) isolates is crucial to ascertain outbreaks, as well as to limit their spread. The current reference method for this purpose is multilocus sequence typing (MLST), which is laborious and expensive. Consequently, alternative typing methods are gaining attention, such as Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS). METHODS: This study sought to analyze MALDI-TOF MS as a typing method using 44 CPKP isolates that were well characterized by MLST. The most common types of samples from which these pathogens were isolated were skin and soft tissues (32%) and urine (29%). Half of the CPKP isolates were from hospitalized patients. Two approaches were followed for the analysis of the mass peak data obtained by MALDI-TOF MS. The first using all peaks obtained and the second using a selection of 21 characteristic peaks. RESULTS: The selection of 21 characteristic peaks showed greater discrimination power for ST11 and ST101. Principal component analysis (PCA) indicated that this dataset could be efficiently grouped with lineal classifiers. A Support Vector Machine (SVM) was chosen for this purpose after checking its capacity to classify bacterial strains on the basis of MALDI-TOF MS information. CONCLUSION: SVM was able to discriminate between ST11 and ST101 with high accuracy. In conclusion, our results reveal MALDI-TOF MS as a promising alternative technique for typing of CPKP isolates.

Panuveitis and Optic Neuritis as a Possible Initial Presentation of the Novel Coronavirus Disease 2019 (COVID-19).

OBJECTIVE: To describe the ocular manifestations in a case of novel coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: A case of unilateral panuveitis and optic neuritis as initial presentation of COVID-19. RESULTS: As it is published, angiotensin-converting-enzyme-2 receptors can be found in many organs, such as the eyes, nerves, and vessels, so extrapulmonary involvement would be expected. According to current evidence and clinical characteristics of the patient, uveitis and optic neuritis could be produced by the virus. CONCLUSIONS: It is fundamental to consider panuveitis and optic neuritis as an unusual presentation of ocular involvement in COVID-19 so proper care can be given to the patients.

Phylogeny of G9 rotavirus genotype: a possible explanation of its origin and evolution.

BACKGROUND: G9 rotavirus genotype was isolated in the 1980s and re-emerged without a clear explanation in the mid-1990s as one of the most frequently occurring genotypes with distinct genetic and molecular characteristics. OBJECTIVES: To study the G9 genotype sequence polymorphisms in Spain and compare them with the human and porcine G9 VP7 genes from the rest of the world. Complete phylogenetic analyses have been done to better characterize G9 genotypes, their relationships and evolution. STUDY DESIGN: Twelve G9 VP7 genes from Spanish patients were sequenced and compared with 240 G genotype sequences. Nucleotide and amino acid sequence similarity percentages and neighbour-joining dendrograms were used to establish a new phylogenetic analysis. RESULTS: Eight of the 12 Spanish sequenced samples had different nucleotide translated region sequences, which yielded only five different proteins. New nucleotide and amino acid sequence comparisons were made that differed from previously described results. CONCLUSIONS: Spanish G9 genotype sequences have similar structure of those belonging to lineage III as the majority of the G9 sequences and share amino acid motifs with other sequences. The phylogenetic analyses of G9 genotypes confirmed the existence of 6 lineages, but did not confirm the 11 sublineages previously reported.

Efficacy of delafloxacin alone and incombination with cefotaxime againstcefotaxime non-susceptible invasive isolatesof Streptococcus pneumoniae / Eficacia de delafloxacino solo y en combinación con cefotaxima frente a aislados invasivos de Streptococcus pneumoniae no sensible acefotaxima

Objectives. We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP). Material and methods. A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method. Results. Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains. Conclusions. CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method. (AU)

Objetivos. Evaluamos la actividad in vitro de delafloxacino y la sinergia entre cefotaxima y delafloxacino entre aislados invasivos de Streptococcus pneumoniae no sensibles a cefotaxima (SPNSC). Material y métodos. Se estudiaron un total de 30 SPNSC (CIM de cefotaxima > 0,5 mg/L). El serotipado se realizó mediante la reacción Pneumotest-Latex y Quellung. Las concentraciones mínimas inhibitorias (CMI) de delafloxacino, levofloxacino, penicilina, cefotaxima, eritromicina y vancomicina se determinaron mediante tiras de difusión en gradiente (GDS). La actividad sinérgica de delafloxacino y cefotaxima frente aislados clínicos de S. pneumoniae se evaluó mediante el método cruzado GDS. Resultados. Delafloxacino mostró una mayor actividad neumocócica que su comparador levofloxacino (CIM50, 0,004 versus 0,75 mg/L y MIC90, 0,047 versus > 32 mg/L). Se identificó resistencia a delafloxacino en 7/30 (23,3%) aislados, pertenecientes a los serotipos 14 y 9V. Se detectó sinergia entre delafloxacino y cefotaxima en 2 cepas (serotipos 19A y 9V). No se observó antagonismo. La adición de delafloxacino aumentó la actividad de cefotaxima en todos los aislados. La sensibilidad a delafloxacino se restableció en 5/7 (71,4%) cepas. Conclusiones. SPNSC mostraron una susceptibilidad a delafloxacino del 76,7%. Se observaron interacciones sinérgicas in vitro entre delafloxacino y cefotaxima entre SPNSC mediante el método cruzado GDS. (AU)