Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004-2024.

The increasing importance of azaheterocyclic phosphonates in the agrochemical, synthetic, and medicinal field has provoked an intense search in the development of synthetic routes for obtaining novel members of this family of compounds. This updated review covers methodologies established since 2004, focusing on the synthesis of azaheterocyclic phosphonates, of which the phosphonate moiety is directly substituted onto to the azaheterocyclic structure. Emphasizing recent advances, this review classifies newly developed synthetic approaches according to the ring size and providing information on biological activities whenever available. Furthermore, this review summarizes information on various methods for the formation of C-P bonds, examining sustainable approaches such as the Michaelis-Arbuzov reaction, the Michaelis-Becker reaction, the Pudovik reaction, the Hirao coupling, and the Kabachnik-Fields reaction. After analyzing the biological activities and applications of azaheterocyclic phosphonates investigated in recent years, a predominant focus on the evaluation of these compounds as anticancer agents is evident. Furthermore, emerging applications underline the versatility and potential of these compounds, highlighting the need for continued research on synthetic methods to expand this interesting family.

Thorough QT/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults.

Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia's QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.

Molecular design and evaluation of aza-polycyclic carbamoyl pyridones as HIV-1 integrase strand transfer inhibitors.

Integrase strand transfer inhibitors (INSTIs) are the most prescribed anchor drug in antiretroviral therapy. Today, there is an increasing need for long-acting treatment of HIV-1 infection. Improving drug pharmacokinetics and anti-HIV-1 activity are key to developing more robust inhibitors suitable for long-acting formulations, but 2nd-generation INSTIs have chiral centers, making it difficult to conduct further exploration. In this study, we designed aza-tricyclic and aza-bicyclic carbamoyl pyridone scaffolds which are devoid of the problematic hemiaminal stereocenter present in dolutegravir (DTG). This scaffold hopping made it easy to introduce several substituents, and evolving structure-activity studies using these scaffolds resulted in several leads with promising properties.

Coumarin-azasugar-benzyl conjugates as non-neurotoxic dual inhibitors of butyrylcholinesterase and cancer cell growth.

We have applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to prepare a library of ten coumarin-azasugar-benzyl conjugates and two phthalimide-azasugar-benzyl conjugates with potential anti-Alzheimer and anti-cancer properties. The compounds were evaluated as cholinesterase inhibitors, demonstrating a general preference, of up to 676-fold, for the inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE). Nine of the compounds behaved as stronger BuChE inhibitors than galantamine, one of the few drugs in clinical use against Alzheimer's disease. The most potent BuChE inhibitor (IC50 = 74 nM) was found to exhibit dual activities, as it also showed high activity (GI50 = 5.6 ± 1.1 µM) for inhibiting the growth of WiDr (colon cancer cells). In vitro studies on this dual-activity compound on Cerebellar Granule Neurons (CGNs) demonstrated that it displays no neurotoxicity.

BF2-Bridged Azafulvene Dimer-Based 1064 nm Laser-Driven Superior Photothermal Agent for Deep-Seated Tumor Therapy.

Small organic photothermal agents (PTAs) with absorption bands located in the second near-infrared (NIR-II, 1000-1700 nm) window are highly desirable for effectively combating deep-seated tumors. However, the rarely reported NIR-II absorbing PTAs still suffer from a low molar extinction coefficient (MEC, ϵ), inadequate chemostability and photostability, as well as the high light power density required during the therapeutic process. Herein, we developed a series of boron difluoride bridged azafulvene dimer acceptor-integrated small organic PTAs. The B-N coordination bonds in the π-conjugated azafulvene dimer backbone endow it the strong electron-withdrawing ability, facilitating the vigorous donor-acceptor-donor (D-A-D) structure PTAs with NIR-II absorption. Notably, the PTA namely OTTBF shows high MEC (7.21×104 M-1 cm-1), ultrahigh chemo- and photo-stability. After encapsulated into water-dispersible nanoparticles, OTTBF NPs can achieve remarkable photothermal conversion effect under 1064 nm irradiation with a light density as low as 0.7 W cm-2, which is the lowest reported NIR-II light power used in PTT process as we know. Furthermore, OTTBF NPs have been successfully applied for in vitro and in vivo deep-seated cancer treatments under 1064 nm laser. This study provides an insight into the future exploration of versatile D-A-D structured NIR-II absorption organic PTAs for biomedical applications.

Dissipation, residues, and evaluation of processing factor for spirotetramat and its formed metabolites during kiwifruit growing, storing, and processing.

Spirotetramat is widely used around the world to control sucking pests and may form in agricultural products. In the current study, the dissipation, residues, and evaluation of processing factor (PF) for spirotetramat and its formed metabolites were investigated during kiwifruit growing, storing, and processing. The residue analysis method was established based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with a QuEChERS method to detect the residues of spirotetramat and its metabolites in kiwifruit and its processed products. The method provided recoveries of 74.7-108.7%, and the relative standard deviations (RSDs) were 0.6-13.1%. The LOQs of spirotetramat and its four metabolites were 1 µg kg-1. The degradation of spirotetramat was best fitted for the first-order kinetics model with a half-life of 9.90-10.34 days in the field and 24.75-30.13 days during storage. Residues of spirotetramat and its formed metabolites in kiwifruit would not pose dietary risk to consumers. Moreover, the peeling and fermentation were the highest removal efficiency for the spirotetramat and its formed metabolite residues during processing. The PF values calculated after each individual process were < 1, indicating a significant reduction of residues in different processing processes of kiwifruit. The spirotetramat was degraded during kiwifruit wine-making process with half-lives of 3.36-4.91 days. B-enol and B-keto were the main metabolites detected in kiwifruit and its processed products. This study revealed the residues of spirotetramat and its formed metabolites in kiwifruit growing, storing, and processing, which helps provide reasonable data for studying the dietary risk factors of kiwifruits and products.

Synthesis and stability of the [45Ti]Ti-DOTA complex: en route towards aza-macrocyclic 45Ti-based radiopharmaceuticals.

We report the use of DOTA as a chelator for titanium. The resulting complex is fully characterised and in vitro stability studies reveal its high kinetic inertness against transmetallation and transchelation. The radiolabeling of DOTA with 45Ti, via a guaiacol-based liquid-liquid extraction method, leads to a high radiochemical conversion up to 98%.

Residual estimation of spirotetramat and its metabolites in chilli and soil by LC-MS/MS.

Two applications of spirotetramat were done to study the dissipation and persistence of spirotetramat and its four different metabolites in chilli and soil at 10 days interval. Total spirotetramat residues were estimated by LC-MS/MS instrument. The mean initial deposits of total spirotetramat after application of spirotetramat 15.31 OD @ 60 (X dose), 75 (1.25 × dose) and 120 (2 × dose) g a.i. ha-1 on green chilli were found to vary from 0.38 to 0.83 mg kg-1 during the initial year. Spirotetramat and its metabolite residues in green chilli were found to be below limit of quantification (0.01 mg kg-1) after 15 days of application. The spirotetramat cis enol (the major metabolite) was formed in both the soil and the plant. The residues of spirotetramat-monohydroxy were below LOQ irrespective of any substrate during the estimation. In soil, the total initial spirotetramat deposits for the 1st year were found 0.09 for X dose, 0.12 for 1.25 × dose and 0.20 mg kg-1 for 2 × dose. After 3 days for both X and 1.25 × doses and 5 days for 2 × dose, the total spirotetramat residues were below LOQ. The spirotetramat's half-life values have been determined to be between 3.19 and 3.93 days and 1.00 and 1.59 days, respectively, in soil and green chilli fruits. One day waiting period is proposed for the safe consumption of green chilli when the spirotetramat was applied irrespective of the dose.

Insights into spirotetramat-induced thyroid disruption during zebrafish (Danio rerio) larval development: An integrated approach with in vivo, in vitro, and in silico analyses.

Spirotetramat (SPT), a tetronic acid-derived insecticide, is implicated in reproductive and lipid metabolism disorders, as well as developmental toxicity in fish. While these effects are documented, the precise mechanisms underlying its developmental toxicity are not fully elucidated. In this study, zebrafish embryos (2 h post-fertilization, hpf) were exposed to four concentrations of SPT (0, 60, 120, and 240 µg/L) until 21 dpf (days post-fertilization). We delved into the mechanisms by examining its potential disruption of the thyroid endocrine system, employing in vivo, in vitro, and in silico assays. The findings showed notable developmental disturbances, including reduced hatching rates, shortened body lengths, and decelerated heart rates. Additionally, there was an increase in malformations and a decline in locomotor activity. Detailed analyses revealed that SPT exposure led to elevated thyroid hormone levels, perturbed the hypothalamic-pituitary-thyroid (HPT) axis transcript levels, amplified deiodinase type I (Dio1) and deiodinase type II (Dio2) activities, and both transcriptionally and proteomically upregulated thyroid receptor beta (TRß) in larvae. Techniques like molecular docking and surface plasmon resonance (SPR) confirmed SPT's affinity for TRß, consistent with in vitro findings suggesting its antagonistic effect on the T3-TR complex. These insights emphasize the need for caution in using tetronic acid-derived insecticides.

Discovery of Novel Azaindoles as Potent and Selective PI3Kδ Inhibitors for Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system and the unmet need for MS treatment demands new therapeutic development. Particularly, PI3Kδ is a high-value target for autoimmune disease, while the investigation of PI3Kδ inhibitors for MS therapy is relatively scarce. Herein, we report a novel class of azaindoles as PI3Kδ inhibitors for MS treatment. Compound 31, designed via nitrogen bioisosterism, displayed excellent PI3Kδ inhibitory activity and selectivity. In vitro assay showed that 31 exhibited superior activity on T lymphocytes to inhibit the proliferation of CD4+, CD8+, and CD3+ T cells. In the experimental autoimmune encephalomyelitis (EAE) model, 31 showed a comparable therapeutical efficacy with Dexamethasone to significantly ameliorate EAE symptoms. Mechanistic studies showed that compound 31 could significantly inhibit the PI3K/AKT/mTOR signaling pathway and inhibited T-cell proliferation and differentiation. Overall, this work provides a new structural PI3Kδ inhibitor and a new vision for MS therapy.

Residue behavior and consumer risk assessment of spirotetramat and chlorpyrifos on cabbage heads and cropped soil.

A field experiment following good agricultural practices was laid out to study the dissipation of spirotetramat (90 g a.i. ha-1 and 180 g a.i. ha-1) and chlorpyrifos (400 g a.i. ha-1 and 800 g a.i. ha-1) on cabbage heads and soil. Samples were processed using quick, easy, cheap, effective, rugged, and safe (QuEChERS) method for residue estimation of spirotetramat and chlorpyrifos, which were further detected using HPLC-PDA and GC-FPD respectively. The residues of spirotetramat on cabbage heads reached below detection limit (BDL) (< 0.05 mg kg-1) on 7th and 10th day and for chlorpyrifos, BDL (< 0.01 mg kg-1) was achieved on 10th and 15th day for X and 2X dose, respectively. On 20th day after second spray, residues in soil were found to be BDL for both the pesticides. Half-life of spirotetramat and chlorpyrifos was found to be 3 and 2 days, respectively while a safe pre-harvest interval (PHI) of 9 days for spirotetramat and 10 days for chlorpyrifos is suggested on cabbage. The dietary risk assessment studies for various age groups of Indian population, ascertained safety of treated cabbage heads for consumption, as current study revealed that hazard quotient (HQ) < 1 and theoretical maximum dietary intake (TMDI) < maximum permissible intake (MPI) for both the pesticides at respective PHI.

Short- and long-term effects of commercial formulations of imidacloprid, spirotetramat, and mixtures of these active ingredients on pupae of Diaeretiella rapae (Hymenoptera: Braconidae) and its progeny.

BACKGROUND: Compatibility studies of insecticides and natural enemies usually focus on short-term lethal effects, without considering the long-term sublethal effects (including progeny). Even less-explored are the effects of commercial insecticides formulated with more than one active product. Short- and long-term lethal and sublethal effects were studied for the first time on the progeny of commercial formulations of spirotetramat, imidacloprid and a commercial mixture of these active ingredients on pupae of Diaeretiella rapae (M'ntosh) (Hymenoptera: Braconidae), an endoparasitoid of aphids considered to be a potential biological control agent. Insecticides were exposed topically on aphid mummies in which the parasitoid was in the pupal stage. RESULTS: Imidacloprid reduced adult emergence by more than 30% and prolonged intra-host development time with respect to control from half the maximum recommended field dose (MFRD). Spirotetramat and commercial mixture only showed significant effects on these endpoints at doses above the MFRD. The tested formulations did not affect adult longevity, sex ratio, and percentage of parasitism in the exposed generation. At low concentrations the active ingredients in the commercial mixture behave synergistically, whereas at medium and high concentrations they behave antagonistically. Considering the 10% lethal dose (LD10), imidacloprid showed the highest hazard coefficient, whereas the commercial mixture was more hazardous when considering the LD50 and LD90. The commercial mixture and imidacloprid induced higher adult emergence and altered the sex ratio in the progeny. CONCLUSIONS: The following order of toxicity on D. rapae can be established: imidacloprid > commercial mixture > spirotetramat. Joint use of this species with imidacloprid and commercial mixture should be avoided in integrated pest management programs. © 2024 Society of Chemical Industry.

Basal levels of biochemical biomarkers in the freshwater prawn Palaemon argentinus and their alterations due to the exposure of both insecticides cypermethrin and spirotetramat.

The aim of this study was to evaluate the sensitivity of the prawn Palaemon argentinus to the pyrethroid cypermethrin (CYP) and the tetramic acid spirotetramat (STM). These treatments were compared with prawns collected at a reference site to define their basal physiological state. Initially, physicochemical parameters and several pollutants at the selected site were analyzed. The LC50-96 h was determined in adult prawns. Then, prawns were exposed for 96 h to sublethal concentrations of CYP (0.0005 µg/l) and STM (0.44 mg/l) to evaluate the effects on some biochemical endpoints. A treatment combining both pesticides was also added at 5 % of these values. Controls with and without solvent (acetone) were included. The LC50-96 h values were 0.005 µg/l and 4.43 mg/l for CYP and STM, respectively. Moreover, some biomarkers linked to oxidative and energy metabolism were analyzed in the hepatopancreas and muscle of both essayed prawns and those at the basal state. The STM caused a significant decrease in total protein content (32 %) in contrast to the increase of protein carbonyl content (71 %) (p < 0.05). Also, glutathione S-transferase (52 %) and catalase (61 %) activities in the hepatopancreas of exposed prawns were higher compared to both the control and state basal groups (p < 0.05). In muscle, only a significant decrease in the lactate content (69 %) was caused by STM (p < 0.05). In addition, CYP caused a significant increase in the lactate dehydrogenase activity (110 %) in muscle and triacylglycerol content (73 %) in the hepatopancreas (p < 0.05). The integrated biomarker index (IBRv2) analysis showed that STM caused greater damage than CYP. Besides, the combined treatment showed an antagonistic interaction between both insecticides. The differential response of biomarkers to both CYP and STM exposure with respect to their basal levels shows a high sensitivity of P. argentinus demonstrating its potential role as a bioindicator organism.

Streptococcus pneumoniae: sensibilidade a penicilina e moxifloxacina / Streptococcus pneumoniae: susceptibility to penicillin and moxifloxacin

OBJETIVO: Determinar a concentração inibitória mínima (CIM) de penicilina parenteral e moxifloxacina contra cepas de Streptococcus pneumoniae isoladas em um centro hospitalar. Métodos: Estudo in vitro prospectivo de 100 isolados de S. pneumoniae coletados de pacientes tratados entre outubro de 2008 e julho de 2010 no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, em São Paulo (SP). Os isolados foram obtidos de culturas do trato respiratório e de amostras de sangue não relacionadas a infecções meníngeas e foram testados quanto à suscetibilidade a penicilina e moxifloxacina por E test. As interpretações categóricas de CIM foram baseadas em padrões atualizados. RESULTADOS: Todos os isolados foram suscetíveis a penicilina parenteral (CIM < 2 µg/mL) e, consequentemente, eram também suscetíveis a amoxicilina, ampicilina, cefalosporinas de terceira e quarta geração e ertapenem. Quanto à moxifloxacina, 99 por cento das cepas de S. pneumoniae também foram suscetíveis, e somente uma teve CIM = 1,5 µg/mL (intermediário). Conclusões: Nossos resultados mostraram altas taxas de sensibilidade a penicilina parenteral e moxifloxacin nos isolados de S. pneumoniae não relacionados a meningite, o que difere de relatos internacionais. Relatos sobre resistência a penicilina devem ser baseados em pontos de corte atualizados para isolados não relacionados a meningite a fim de guiar a escolha terapêutica antimicrobiana e melhorar a predição dos desfechos clínicos.

OBJECTIVE: To determine the minimum inhibitory concentrations (MICs) of parenteral penicillin and moxifloxacin against Streptococcus pneumoniae strains isolated at a hospital center. METHODS: In-vitro, prospective study involving 100 S. pneumoniae isolates collected from patients who had been treated, between October of 2008 and July of 2010, at the Hospital das Clínicas complex of the University of São Paulo School of Medicine, located in the city of São Paulo, Brazil. The isolates were obtained from respiratory tract cultures or blood samples unrelated to meningeal infections, and they were tested for penicillin and moxifloxacin susceptibility by E-test. The MIC category interpretations were based on updated standards. RESULTS: All isolates were fully susceptible to parenteral penicillin (MIC < 2 µg/mL), and, consequently, they were also susceptible to amoxicillin, ampicillin, third/fourth generation cephalosporins, and ertapenem. Of the S. pneumoniae strains, 99 percent were also susceptible to moxifloxacin, and only one strain showed an MIC = 1.5 µg/mL (intermediate). CONCLUSIONS: Our results showed high susceptibility rates to parenteral penicillin and moxifloxacin among S. pneumoniae isolates unrelated to meningitis, which differs from international reports. Reports on penicillin resistance should be based on updated breakpoints for non-meningitis isolates in order to guide the selection of an antimicrobial therapy and to improve the prediction of the clinical outcomes.

Rhodococcus equi infection after reduction mammaplasty in an immunocompetent patient / Infección por Rhodococcus equi luego de cirugía de reducción mamaria en huésped inmunocompetente

The majority of infections caused by R. equi occur in hosts with some degree of cell-mediated immunodeficiency. Immunocompetent individuals are infrequently affected and usually present with localized disease. Infections of the skin or related structures are uncommon and are usually related to environmental contamination. The microbiology laboratory plays a key role in the identification of the organism since it may be mistaken for common skin flora. We describe a 31 year-old woman without medical problems who presented nine weeks after breast reduction with right breast cellulitis and purulent drainage from the surgical wound. She underwent incision and drainage, and cultures of the wound yielded Rhodococcus equi. The patient completed six weeks of antimicrobial therapy with moxifloxacin and rifampin with complete resolution.

La mayoría de las infecciones causadas por Rhodococcus equi ocurren en huéspedes con algún grado de inmunodeficiencia celular. Los individuos inmunocompetentes son afectados con baja frecuencia y suelen presentarse con enfermedad localizada. Las infecciones de la piel o partes blandas son poco frecuentes y están usualmente relacionadas con contaminación ambiental. El laboratorio de microbiología juega un papel clave en la identificación del organismo, ya que este puede confundirse con flora normal de la piel. Se describe una mujer de 31 años sin problemas médicos que consultó nueve semanas después de haber sido sometida a cirugía de reducción mamaria, con celulitis del seno derecho y drenaje purulento de la herida quirúrgica. Se practicó incisión y drenaje quirúrgico y los cultivos de la herida demostraron R. equi. La paciente recibió seis semanas de tratamiento antimicrobiano con moxifloxacina y rifampicina demostrando resolución completa.

Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model

OBJECTIVE: Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer. METHODS: Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA. RESULTS: Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model. CONCLUSION: Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer.

Conjuntivite por Achromobacter xylosoxidans: relato de caso / Conjunctivitis due to Achromobacter xylosoxidans: case report

Relatamos um caso de conjuntivite ocasionada por Achromobacter xylosoxidans em paciente imunocompetente usuária de lentes de contato rígidas. A bactéria foi isolada da solução utilizada para a desinfecção das lentes bem como do raspado conjuntival. A. xylosoxidans tem sido descrita em infecções oportunistas em pacientes imunodeprimidos, contudo pode ser confundida com outros bacilos gram-negativos, principalmente Pseudomonas aeruginosa, isoladas de infecções oculares em pacientes imunocompetentes. Devido ao reduzido perfil de sensibilidade aos antimicrobianos demonstrado pelo A. xylosoxidans, torna-se importante a identificação deste agente etiológico em quadros de conjuntivite.

We report here a case of conjunctivitis in an immunocompetent patient due to Achromobacter xylosoxidans, which was associated with the use of rigid contact lenses. The bacteria were isolated from the scraped conjunctival swab as well as from the lens cleaning fluid. A. xylosoxidans is an opportunistic pathogen, especially in immunocompromised patients; however, in isolates of ocular infections, from immunocompetent patients, it may be confused with other gram-negative organisms, particularly Pseudomonas aeruginosa. Due to an increased resistance against different antimicrobial agents, A. xylosoxidans must be fully identified and differentiated from other gram-negative isolates from ocular infections.

Infectious keratitis secondary to Histoplasma capsulatum: the first case reports in humans

The authors report an unusual case of fungal keratitis caused by Histoplasma capsulatum in a male immunocompetent patient. PCR confirmed the presence of the fungus DNA in the material studied. To our knowledge this is the first reported case in humans described all over the world.

Fluoroquinolone susceptibilities to methicillin-resistant and susceptible coagulase-negative Staphylococcus isolated from eye infection

PURPOSE: To evaluate the fluoroquinolone susceptibilities of ocular isolate coagulase-negative staphylococci (CoNS), identified at the Microbiology Laboratory - UNIFESP. DESIGN: Experimental laboratory investigation. METHODS: The minimum inhibitory concentrations (MICs) of 21 strains of methicillin-resistant coagulase-negative staphylococci (MRCoNS) and 22 methicillin-sensitive coagulase-negative staphylococci (MSCoNS) to ciprofloxacin, ofloxacin, gatifloxacin and moxifloxacin were determined, using the E-test method standardized by the Clinical and Laboratory Standards Institute (CLSI/NCCLS). RESULTS: The MIC90s (µg/ml) for the second generation of tested fluoroquinolones were higher than the fourth generation, especially for the methicillin-resistant coagulase-negative staphylococci group. CONCLUSION: Our results indicate that methicillin-sensitive coagulase-negative staphylococci are more susceptible to quinolones than are methicillin-resistant coagulase-negative staphylococci and that fourth generation fluoroquinolones appear to be more potent, affecting even coagulase-negative staphylococcal strains resistant to second generation fluoroquinolones.

OBJETIVOS: Avaliar a suscetibilidade a fluorquinolonas dos Staphylococcus coagulase-negativo (SCoN) identificados no Laboratório de Microbiologia Ocular da Unifesp. MÉTODOS: Foi determinada a concentração inibitória mínima de 21 cepas de SCoN meticilina-resistentes e 22 meticilina-sensíveis para ciprofloxacina, ofloxacina, gatifloxacina e moxifloxacina, utilizando o E-test estandartizado pelo CLSI/NCCLS. RESULTADOS: Os MIC90 (µg/ml) de 43 SCoN isolados para fluorquinolonas de segunda geração foram maiores do que os de quarta geração, principalmente para o grupo dos meticilina-resistentes. CONCLUSÃO: Nossos resultados indicam que Staphylococcus coagulase-negativo meticilina-sensíveis são mais suscetíveis às quinolonas do que os Staphylococcus coagulase-negativo meticilina-resistentes, fluorquinolonas de quarta geração parecem ser mais potentes, cobrindo inclusive cepas de Staphylococcus coagulase-negativo resistentes à segunda geração de fluorquinolonas.