Antimicrobial susceptibility of Viridians Group of Streptococci isolated from infective endocarditis patients from 2018 to 2023.

INTRODUCTION: Viridans Group of Streptococci (VGS) are heterogeneous alpha hemolytic Streptococci that form commensal flora in the oral cavity, upper respiratory tract, gastrointestinal tract and female genital tract and are potential pathogens that can cause serious infections like infective endocarditis and bacteremia. Penicillin or Ceftriaxone is the recommended first line agent for definitive therapy of VGS endocarditis. Alteration in penicillin binding proteins can decrease the susceptibility of VGS to penicillin and other beta-lactam agents and complicate antimicrobial therapy for serious VGS infections like Infective endocarditis. The aim of our study was to determine the antimicrobial susceptibility pattern of viridians group Streptococci isolated from blood samples of infective endocarditis patients from April 2018 to September 2023 against betalactam and other agents. MATERIAL AND METHODS: Three sets of blood cultures with 8-10 ml per bottle were collected from suspected infective endocarditis and incubated in automated blood culture system (BACTEC from BD diagnostics). The broth from positive bottles was streaked on Blood agar, Chocolate agar and MacConkey agar plates and incubated at 37°C. Alpha hemolytic Streptococci that grew after 24-48 h were further identified and antimicrobial susceptibility determined by Vitek 2 system. RESULTS: A total of 100 VGS was isolated from blood samples of Infective endocarditis patients. The species most commonly isolated in our study was S. sanguinis (25%) and S.mitis/oralis group (23%) followed by Non speciated Viridans Streptococci (17%). The lowest penicillin susceptibility ie. PEN MIC <0.12 µg/ml of 40% was observed in S. alactolyticus group, followed by S. mitis (52%) and S. gallolyticus (56%). S. mitis/oralis group showed the lowest susceptibilities to betalactam antibiotics among all speciated and non speciated VGS. CONCLUSION: Infective endocarditis carries a very high mortality and morbidity and the emergence of resistance to betalactam agents like penicillin will only narrow available therapeutic options and further challenge the treatment.

Viridans Group Streptococci in Pediatric Leukemia and Stem Cell Transplant: Review of a Risk-stratified Guideline for Empiric Vancomycin in Febrile Neutropenia.

Viridans group streptococci (VGS) are an important cause of sepsis in immunosuppressed children. We reviewed the effectiveness of risk-stratified addition of vancomycin to empiric febrile neutropenia therapy among 107 children with leukemia or undergoing an allogeneic transplant. Of 19 VGS bacteremia episodes, 78.9% were susceptible to risk-stratified antibiotics including 100% from high-risk patients. All blood cultures were flagged positive within 24 hours.

Endocarditis Caused by Highly Penicillin-Resistant Viridans Group Streptococci: Still Room for Vancomycin-Based Regimens.

Optimal treatment options remain unknown for infective endocarditis (IE) caused by penicillin-resistant (PEN-R) viridans group streptococcal (VGS) strains. The aims of this study were to report two cases of highly PEN-R VGS IE, perform a literature review, and evaluate various antibiotic combinations in vitro and in vivo The following combinations were tested by time-kill studies and in the rabbit experimental endocarditis (EE) model: PEN-gentamicin, ceftriaxone-gentamicin, vancomycin-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin. Case 1 was caused by Streptococcus parasanguinis (PEN MIC, 4 µg/ml) and was treated with vancomycin plus cardiac surgery. Case 2 was caused by Streptococcus mitis (PEN MIC, 8 µg/ml) and was treated with 4 weeks of vancomycin plus gentamicin, followed by 2 weeks of vancomycin alone. Both patients were alive and relapse-free after ≥6 months follow-up. For the in vitro studies, except for daptomycin-ampicillin, all combinations demonstrated both synergy and bactericidal activity against the S. parasanguinis isolate. Only PEN-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin demonstrated both synergy and bactericidal activity against the S. mitis strain. Both strains developed high-level daptomycin resistance (HLDR) during daptomycin in vitro passage. In the EE studies, PEN alone failed to clear S. mitis from vegetations, while ceftriaxone and vancomycin were significantly more effective (P < 0.001). The combination of gentamicin with PEN or vancomycin increased bacterial eradication compared to that with the respective monotherapies. In summary, two patients with highly PEN-R VGS IE were cured using vancomycin-based therapy. In vivo, regimens of gentamicin plus either ß-lactams or vancomycin were more active than their respective monotherapies. Further clinical studies are needed to confirm the role of vancomycin-based regimens for highly PEN-R VGS IE. The emergence of HLDR among these strains warrants caution in the use of daptomycin therapy for VGS IE.

Identificación y sensibilidad a los antimicrobianos de aislados de estreptococos del grupo viridans provenientes de pacientes internados en un hospital universitario de la ciudad de Buenos Aires / Identification and antibiotic susceptibility of viridans group streptococci isolates recovered from patients hospitalized at a teaching hospital in Buenos Aires City

Los estreptococos del grupo viridans (EGV) son agentes causales de infecciones localizadas e invasivas. Dada la gravedad de las infecciones producidas por EGV sumada a las escasas comunicaciones actuales en nuestro país, los objetivos de este trabajo fueron la identificación y el estudio de la sensibilidad a los antibióticos de aislados caracterizados como EGV, recuperados de pacientes internados, para actualizar el conocimiento sobre el perfil de resistencia y la epidemiología de las infecciones ocasionadas por EGV. Se recuperaron 132 aislados de EGV en el Hospital de Clínicas «José de San Martín¼ en el período 2011-2015. La identificación se realizó mediante pruebas convencionales y espectrometría de masas (Matrix Assisted Laser Desorption Ionization - Time of Flight Mass Spectrometry). El grupo Streptococcus anginosus fue el más frecuente (42%) seguido por el grupo Streptococcus mitis (33%). Dentro del grupo S. mitis se excluyó a Streptococcus pneumoniae. El 100% de los aislados fue sensible a ertapenem, linezolid y vancomicina; el 96,9% a cef-triaxona y cefepima. Se encontró un 25,8% de resistencia a penicilina (I+R) fundamentalmente en aislados de grupo S. mitis. La resistencia a tetraciclina fue del 27,2% y solo 2/132 aislados fueron resistentes a levofloxacina. Los valores de CIM de gentamicina oscilaron entre 0,5 y 32 -og/ml. El 17,4% de los aislados presentó resistencia a eritromicina sin diferencia significativa en la distribución de fenotipos M y MLS. Los resultados muestran la importancia de la vigilancia continua de las infecciones producidas por estos microorganismos con el fin de generar aportes para la elección de la terapia antibiótica adecuada.

Members of the viridans group streptococci (VGS) are the cause of local and invasive infections. Due to the severity of these infections and taking into account that reports regarding epidemiological aspects are scarce, the aims of this work were the identification and the study of the antibiotic susceptibility profiles of the isolates recovered from patients that were hospitalized in order to find out about the resistance level and the epidemiology of infections in which VGS are involved. A hundred and thirty two isolates identified as VGS were isolated at Hospital de Clínicas «José de San Martín¼ during the period 2011-2015. The identification was performed by biochemical test and mass spectrometry by Matrix Assisted Laser Desorption Ionization -Time of Flight Mass Spectrometry. Streptococcus anginosus group was prevalent (42%) followed by Streptococcus mitis group (33%). In the latter, isolates of Streptococcus pneumoniae were excluded. All the VGS isolates were susceptible to ertapenem, meropenem, linezolid and vancomycin; 25.8% were resistant (I+R) to penicillin, being prevalent in the S. mitis group. Regarding ceftriaxone and cefepime 96.9% of the isolates were susceptible. Only two isolates were resistant to levofloxacin, 27.2% to tetracycline and it was not found high level resistance to gentamycin (MIC range 0.5-32 µg/ml). Resistance to erythromycin was 17.4% with no significant difference between M and MLS phenotypes. The most active antibiotics were in addition to ceftriaxone and cefepime, vancomycin, ertapenem, meropenem and linezolid. These results highlight the importance of the continuous surveillance of the infections caused by VGS in order to predict a correct antibiotic therapy.

In vitro effects of commercial mouthwashes on several virulence traits of Candida albicans, viridans streptococci and Enterococcus faecalis colonizing the oral cavity.

Oral microbiota consists of hundreds of different species of bacteria, fungi, protozoa and archaea, important for oral health. Oral mycoses, mostly affecting mucosae, are mainly caused by the opportunistic pathogen Candida albicans. They become relevant in denture-wearers elderly people, in diabetic patients, and in immunocompromised individuals. Differently, bacteria are responsible for other pathologies, such as dental caries, gingivitis and periodontitis, which affect even immune-competent individuals. An appropriate oral hygiene can avoid (or at least ameliorate) such pathologies: the regular and correct use of toothbrush, toothpaste and mouthwash helps prevent oral infections. Interestingly, little or no information is available on the effects (if any) of mouthwashes on the composition of oral microbiota in healthy individuals. Therefore, by means of in vitro models, we assessed the effects of alcohol-free commercial mouthwashes, with different composition (4 with chlorhexidine digluconate, 1 with fluoride, 1 with essential oils, 1 with cetylpyridinium chloride and 1 with triclosan), on several virulence traits of C. albicans, and a group of viridans streptococci, commonly colonizing the oral cavity. For the study here described, a reference strain of C. albicans and of streptococci isolates from pharyngeal swabs were used. Chlorhexidine digluconate- and cetylpyridinium chloride-containing mouthwashes were the most effective in impairing C. albicans capacity to adhere to both abiotic and biotic surfaces, to elicit proinflammatory cytokine secretion by oral epithelial cells and to escape intracellular killing by phagocytes. In addition, these same mouthwashes were effective in impairing biofilm formation by a group of viridans streptococci that, notoriously, cooperate with the cariogenic S. mutans, facilitating the establishment of biofilm by the latter. Differently, these mouthwashes were ineffective against other viridans streptococci that are natural competitors of S. mutans. Finally, by an in vitro model of mixed biofilm, we showed that mouthwashes-treated S. salivarius overall failed to impair C. albicans capacity to form a biofilm. In conclusion, the results described here suggest that chlorhexidine- and cetylpyridinium-containing mouthwashes may be effective in regulating microbial homeostasis of the oral cavity, by providing a positive balance for oral health. On the other side, chlorhexidine has several side effects that must be considered when prescribing mouthwashes containing this molecule.

Microbiology and clinical characteristics of viridans group streptococci in patients with cancer

ABSTRACT This study assessed the microbiology, clinical syndromes, and outcomes of oncologic patients with viridans group streptococci isolated from blood cultures between January 1st, 2013 and December 31st, 2016 in a referral hospital in Mexico using the Bruker MALDI Biotyper. Antimicrobial sensitivity was determined using BD Phoenix 100 according to CLSI M100 standards. Clinical information was obtained from medical records and descriptive analysis was performed.Forty-three patients were included, 22 females and 21 males, aged 42 ± 17 years. Twenty (46.5%) patients had hematological cancer and 23 (53.5%) a solid malignancy. The viridans group streptococci isolated were Streptococcus mitis, 20 (46.5%); Streptococcus anginosus, 14 (32.6%); Streptococcus sanguinis, 7 (16.3%); and Streptococcus salivarius, 2 (4.7%). The main risk factors were pyrimidine antagonist chemotherapy in 22 (51.2%) and neutropenia in 19 (44.2%) cases, respectively. Central line associated bloodstream infection was diagnosed in 18 (41.9%) cases. Septic shock occurred in 20.9% of patients, with an overall mortality of 18.6%. Only four S. mitis revealed penicillin-resistance.Our results are similar to those of other series, identifying these bacteria as emerging pathogens with significant morbidity and mortality in oncologic patients. The MALDI-TOF system increased the rate of viridans group streptococci isolation in this population.

Microbiology and clinical characteristics of viridans group streptococci in patients with cancer.

This study assessed the microbiology, clinical syndromes, and outcomes of oncologic patients with viridans group streptococci isolated from blood cultures between January 1st, 2013 and December 31st, 2016 in a referral hospital in Mexico using the Bruker MALDI Biotyper. Antimicrobial sensitivity was determined using BD Phoenix 100 according to CLSI M100 standards. Clinical information was obtained from medical records and descriptive analysis was performed. Forty-three patients were included, 22 females and 21 males, aged 42 ± 17 years. Twenty (46.5%) patients had hematological cancer and 23 (53.5%) a solid malignancy. The viridans group streptococci isolated were Streptococcus mitis, 20 (46.5%); Streptococcus anginosus, 14 (32.6%); Streptococcus sanguinis, 7 (16.3%); and Streptococcus salivarius, 2 (4.7%). The main risk factors were pyrimidine antagonist chemotherapy in 22 (51.2%) and neutropenia in 19 (44.2%) cases, respectively. Central line associated bloodstream infection was diagnosed in 18 (41.9%) cases. Septic shock occurred in 20.9% of patients, with an overall mortality of 18.6%. Only four S. mitis revealed penicillin-resistance. Our results are similar to those of other series, identifying these bacteria as emerging pathogens with significant morbidity and mortality in oncologic patients. The MALDI-TOF system increased the rate of viridans group streptococci isolation in this population.

Viridans group streptococci bloodstream infections in neutropenic adult patients with hematologic malignancy: Single center experience.

Viridans group streptococci bloodstream infections (VGS BSI) remain a significant cause of mortality and morbidity in patients with severe neutropenia. The goal of our study was to evaluate clinical course and microbiological susceptibility of VGS BSI at our center. Retrospective analysis of all microbiologically documented bloodstream infections caused by VGS during the 9-year time period (from January 2006 until December 2014) was carried out. Only patients with severe neutropenia (< 500/µL) were included in the study. Clinical outcome and microbiological susceptibility pattern of isolates were recorded. Fifty-one individual patients with episode of VGS BSI were identified. The most frequent agent was Streptococcus mitis (23/51 cases, 45.1%). 88.2% (45/51) of patients were on recommended ciprofloxacin prophylaxis. 20/51 (39.2%) of patients suffered from mucositis at the time of diagnosis (10 patients had oral mucositis, 2 patients had bowel mucositis, and 8 patients both). Twenty-six patients (51.0%) had clinically relevant lung damage caused by VGS BSI (i.e., acute lung injury or acute respiratory distress syndrome). Twenty-four (47.0%) patients presented with bilateral lung infiltrated upon chest imaging, and two (4.0%) patients had unilateral lung infiltrates. Three patients (5.9%) died due to VGS BSI until day 28 of observation. No difference in signs of shock syndrome was observed in the patients during transplantation procedures compared to patients without transplantation as well as in a group received previous high-dose chemotherapy with cytosinarabinoside or in patients with mucositis. Only 3/51 of isolates (5.9%) were resistant to penicillin. All isolates were susceptible to empirical treatment. While the penicillin resistance of VGS remains low in middle Europe, initial antibiotic therapy of febrile neutropenia are still effective in most cases. The mortality and complication rates of VGS BSI were comparable to other studies, and no specific risk factor of shock presence could be identified.

Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia.

Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient's quality of life and decrease health care costs.

An approach to a patient with infective endocarditis.

Although infective endocarditis (IE) is relatively uncommon, it remains an important clinical entity with a high in-hospital and 1-year mortality. It is most commonly caused by viridans streptococci. Staphylococcus aureus is responsible for a malignant course of IE and often requires early surgery to eradicate. Other rarer causes are various bacilli, including the HACEK (Haemophilus, Actinobacillus,Cardiobacterium, Eikenella and Kingella spp.) group of organisms and fungi. The clinical presentation varies. Patients may present with a nonspecific illness, valve dysfunction, heart failure (HF) and symptoms due to peripheral embolisation. The diagnosis is traditionally based on the modified Duke criteria and rests mainly on clinical features and to a lesser extent on certain laboratory findings,microbiological assessment and cardiovascular imaging. Identification of the offending micro-organism is not only important from a diagnostic point of view, but also makes targeted antibiotic treatment possible and provides useful prognostic information. A significant proportion of microbiological cultures are negative, frequently owing to the administration of antibiotics prior to appropriate culture.Blood-culture-negative IE poses significant diagnostic and treatment challenges. The course of the disease is frequently complicated, and sequelae include HF, local intracardiac extension of infection (abscess, fistula, pseudoaneurysm), stroke and intracranial haemorrhage due to septic emboli or mycotic aneurysm formation as well as renal injury. Management includes prolonged intravenous antibiotics and consideration for early surgery with removal of infective tissue and valve replacement in patients who have poor prognostic features or complications. Antibiotic administration for at-risk patients to prevent bacteraemia during specific procedures (particularly dental) is recommended to prevent IE. The patient population who would benefit from antibiotic prophylaxis has become increasingly restricted,and guidelines recommend prophylaxis only for patients with cyanotic congenital heart disease, prosthetic heart valves and a previous episode of IE. The management of a patient with IE is challenging and often requires multidisciplinary input from an IE heart team,which includes cardiologists

Synthesis and Biological Evaluation of Curcuminoid Derivatives.

Many curcuminoid derivatives have been reported to have multiple biological activities. The aim of this study was to improve the biological activity of curcuminoids by synthesizing 16 new derivatives which combined cinnamic acids with curcuminoids, and we also analyzed the structure-activity relationship of the new compounds. Almost all the new compounds showed encouraging activity, especially compound 7g. It had much better antioxidant activity than curcuminoids and Vitamin C (VC), and also had the most significant antibacterial activity, which was 5-folder better than ampicillin (one of the best marketed antibiotics) with a minimum inhibitory concentration (MIC) of 0.5 µg/mL against Gram-positive cocci (Staphylococcus aureus and Streptococcus viridans) as well as Escherichia coli and 0.6 µg/mL against Enterobacter cloacae. Compound 7g also showed the greatest anticancer activity with a much lower IC50, which was 0.51 µM against MCF-7, 0.58 µM against HepG-2, 0.63 µM against LX-2, and 0.79 µM against 3T3. The results suggest that these compounds have promising potential as candidates for the treatment of cancer and thus further studies are warranted.

Characteristics of pyogenic odontogenic infection in patients attending Mulago Hospital, Uganda: a cross-sectional study.

BACKGROUND: Predisposing factors of pyogenic odontogenic infection include dental caries, pericoronitis, periodontitis, trauma to the dentition and the supporting structures or complications of dental procedures. The infections are usually polymicrobial involving normal endogenous flora. We characterised pyogenic odontogenic infection in patients attending Mulago Hospital, Uganda. RESULTS: Of the 130 patients, 62 (47.7%) were female. The most frequently involved fascial spaces were: the buccal, 52 (25.4%); submasseteric, 46 (22.4%) and the submandibular space, 36 (17.5%). Dental caries was the most prevalent predisposing factor, particularly of the lower third molar teeth. Viridans Streptococci Group and Staphylococcus aureus were the most frequent bacterial isolates: 23.5% and 19.4%, respectively. All Viridans Streptococci isolates were resistant to penicillin G, sulfamethoxazole/trimethoprim (cotrimoxazole), ampicillin and tetracycline, but susceptible to vancomycin. All Staphylococcus aureus strains were resistant to cotrimoxazole and ampicillin while retaining susceptibility to vancomycin, cefotaxime, linezolid, moxifloxacin and amoxicillin/clavulanate. Thirty five (26.9%) patients were HIV infected and the HIV status did not significantly influence the pattern of odontogenic infection. CONCLUSIONS: Dental caries was the most prevalent predisposing factor for pyogenic odontogenic infection. High prevalence of bacterial resistance to ampicillin and cotrimoxazole suggests the need for regular antibiotic susceptibility tests of isolates and rational use of antibiotics in the management of these infections. Prevention requires strengthening of oral health in the community.

Effect of antibiotic use on bacterial flora of tonsil core in patients with recurrent tonsillitis.

The aim of this study was to investigate the effects of commonly used antibiotics on bacterial flora of the tonsil core. Patients who underwent tonsillectomy for recurrent chronic tonsillitis were included in the study. Three groups were formed: group 1 was treated for 10 days preoperatively with amoxicillin/clavulanic acid; group 2 was treated for 10 days preoperatively with clarithromycin; and group 3 included patients who underwent tonsillectomy without preoperative antibiotic use. The removed palatine tonsils were sent to our microbiology department in sterile tubes for bacteriological analysis. Seventy-three patients (group 1 = 19, group 2 = 20, group 3 = 34 patients) aged 3-18 years (mean 7 years) were included in the study. At least one bacterium was isolated from all tonsils, except for two cases in group 1; the difference in single bacterial growth among groups was not significant (p = 0.06). On the other hand, the numbers of patients with pathogenic bacterial growth was significantly lower in group 2 (n = 2) compared with group 1 (n = 10) and group 3 (n = 27) (p < 0.001). The bacterium isolated most frequently from the tonsils was Streptococcus viridans. Pseudomonas aeruginosa was the only pathogenic bacterium that grew in all three groups. Clarithromycin was more effective than amoxicillin/clavulanic acid in eradicating pathogenic bacteria in the tonsil core. Pseudomonas aeruginosa might be responsible for resistant or recurrent tonsil infections. To prevent endocarditis, antibiotic prophylaxis toward S. viridians, which is the most prevalent bacterium in the tonsil core, should be kept in mind for patients with heart valve damage.

[An analysis of clinical characteristics, etiologies and prognosis of 218 patients with infective endocarditis].

OBJECTIVE: To describe the profile of patients with infective endocarditis (IE) and assess prognostic factors of IE. METHODS: Clinical and etiology data of 218 patients with IE were collected retrospectively from January 2011 to January 2013. The distribution and antimicrobial susceptibilities of pathogens causing IE were evaluated. Prognostic factors associated with IE were determined by univariate and multivariate regression analysis. RESULTS: There were 148 men and 70 women with age of (46.0 ± 14.6) years. Ninety-five (43.6%) of them had heart diseases, including 72 cases (33.0%) of congenital heart disease and 23 cases (10.6%) of chronic rheumatic heart disease. Vegetations were detected by echocardiography in 171 (78.4%) patients. Microorganisms causing IE were identified in 84 cases (38.5%) cases. Streptococcus viridans was the dominant pathogen, accounted for 63.1% of all the pathogens, followed by Staphylococcus (13.1%) and Enterococcus (4.8%). Totally 7/11 Streptococcus viridans was susceptible to penicillin, while 100% susceptible to the third and fourth generation cephalosporins, vancomycin and linezolid. One hundred and eighty cases underwent operations. The in-hospital mortality rate of IE was 3.2%. In univariate regression, health care-associated infection, prosthetic valve, anemia and chest symptoms (distress or pain) were related to the increased risk of mortality in patients with IE, while surgery appeared to be a protective factor. In the logistic regression model, the variables significantly associated with IE prognosis were health care-associated infection (OR = 17.03, 95%CI 1.76-164.75, P = 0.014) and anemia (Hb < 90 g/L) (OR = 13.47, 95%CI 2.46-73.60, P = 0.003) and surgery treatment (OR = 0.17, 95%CI 0.03-0.97, P = 0.047). CONCLUSIONS: Although Streptococcus viridans is the most common pathogen causing IE, the pathogens of IE become versatile. The antibacterial activity of penicillin against Streptococcus viridans is low. Health care-associated infection and anemia are risk factors of IE prognosis, while surgery treatment is a protective factor of severe IE.

Development and validation of a clinical model to predict the presence of ß-lactam resistance in viridans group streptococci causing bacteremia in neutropenic cancer patients.

BACKGROUND: Concern for serious infection due to ß-lactam-resistant viridans group streptococci (VGS) is a major factor driving empiric use of an anti-gram-positive antimicrobial in patients with febrile neutropenia. We sought to develop and validate a prediction model for the presence of ß-lactam resistance in VGS causing bloodstream infection (BSI) in neutropenic patients. METHODS: Data from 569 unique cases of VGS BSI in neutropenic patients from 2000 to 2010 at the MD Anderson Cancer Center were used to develop the clinical prediction model. Validation was done using 163 cases from 2011 to 2013. In vitro activity of ß-lactam agents was determined for 2011-2013 VGS bloodstream isolates. RESULTS: In vitro resistance to ß-lactam agents commonly used in the empiric treatment of febrile neutropenia was observed only for VGS isolates with a penicillin minimum inhibitory concentration (MIC) of ≥ 2 µg/mL. One hundred twenty-nine of 732 patients (17%) were infected with VGS strains with a penicillin MIC ≥ 2 µg/mL. For the derivation and validation cohorts, 98% of patients infected by VGS with a penicillin MIC of ≥ 2 µg/mL had at least 1 of the following risk factors: current use of a ß-lactam as antimicrobial prophylaxis, receipt of a ß-lactam antimicrobial in the previous 30 days, or nosocomial VGS BSI onset. Limiting empiric anti-gram-positive therapy to neutropenic patients having at least 1 of these 3 risk factors would have reduced such use by 42%. CONCLUSIONS: Simple clinical criteria can assist with targeting of anti-gram-positive therapy to febrile neutropenic patients at risk of serious ß-lactam-resistant VGS infection.

Endophthalmitis caused by streptococcal species: clinical settings, microbiology, management, and outcomes.

PURPOSE: To report the clinical settings, antibiotic susceptibilities, and outcomes of endophthalmitis caused by Streptococcus species. DESIGN: Retrospective, observational case series. METHODS: Single-center study evaluating all patients with culture-positive endophthalmitis caused by Streptococcus species between January 1, 2000, and December 31, 2011. RESULTS: Study criteria were met by 63 patients. The most common clinical settings were bleb associated (n = 17; 27%), after intravitreal injection (n = 16; 25%), and after cataract surgery (n = 13; 21%). The isolates were Streptococcus viridans (n = 47; 71%), Streptococcus pneumoniae (n = 13; 21%), and ß-hemolytic Streptococci (n = 5; 8%). Sixty (95%) of 63 isolates were susceptible to vancomycin, 47 (98%) of 48 isolates were susceptible to ceftriaxone (third-generation cephalosporin), and 57 (93%) of 61 isolates were susceptible to levofloxacin (third-generation fluoroquinolone). Between the first and second half of the study, the minimal inhibitory concentration of antibiotics required to inhibit 90% of isolates increased by 1.5-fold for ceftriaxone and 2-fold for levofloxacin and remained the same for vancomycin. Initial treatment was vitreous tap (49; 78%) or pars plana vitrectomy (14; 22%); all received intravitreal antibiotics. Visual acuity outcomes were variable: best-corrected visual acuity was 20/400 or better in 16 (25%) patients and worse than 20/400 in 47 (75%) patients. Evisceration or enucleation was performed in 16 (25%) patients. CONCLUSIONS: Streptococcus isolates generally had high susceptibility rates to commonly used antibiotics. Higher antibiotic minimal inhibitory concentrations were required to inhibit 90% of isolates in vitro in the second half of the study period compared with the first half. Despite prompt treatment, most patients had poor outcomes.

Relapsing bloodstream infections during treatment of acute leukemia.

Acute leukemia (AL) patients may experience more than one episode of bloodstream infection (BSI) caused by the same pathogen during the entire chemotherapy program. In order to identify factors influencing BSI recurrence (R-BSI) during subsequent phases of treatment, we analyzed all BSIs occurring to consecutively treated AL patients during a period of active epidemiologic surveillance at our institution between 2004 and 2011. Two hundred and fifty BSIs were observed in 138 patients receiving more than 1 cycle of chemotherapy. BSI due to the same pathogen recurred in 39/138 (28.3 %) patients. Gram-negative rods (GNRs) accounted for 59.6 % and Gram-positive cocci (GPCs) for 34.4 % of BSI. Four pathogens were involved in R-BSI: Escherichia coli, Pseudomonas aeruginosa, coagulase-negative staphylococci, and Streptococcus viridans. GNRs were significantly more frequent among R-BSI compared to non-relapsing BSI (nR-BSI) [69/94 (73.4 %) vs 70/156 (50.6 %), p < 0.0001]; in particular, E. coli accounted for 67 % of R-BSI vs 32.1 % of nR-BSI (p < 0.0001). Receiving more than four chemotherapy courses and having an extended spectrum ß-lactamase (ESBL)-producing E. coli BSI at any time of treatment were significantly associated to R-BSI. A trend toward a higher mortality among R-BSI patients in comparison with nR-BSI was observed (17.9 and 7.1 %, respectively, p = 0.12). Among AL patients, R-BSI is a frequent phenomenon, which may contribute to the shift of epidemiology toward GNR and to a higher mortality. This should significantly impact the strategies of antibiotic prophylaxis and treatment in patients with AL.

Clinical characteristics and antimicrobial susceptibilities of viridans streptococcal bacteremia during febrile neutropenia in patients with hematologic malignancies: a comparison between adults and children.

BACKGROUND: This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies. METHODS: The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively. A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB. RESULTS: A total of 202 episodes (141 in adults, 61 in children) of VSB were identified. Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB. For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%). Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004). The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children. Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002). However, in multivariate analysis, cefepime susceptibility had no impact on clinical outcome. CONCLUSIONS: There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility. Hence, different antibiotic treatment strategies may not be necessary.

Clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia in children with febrile neutropenia.

PURPOSE: This retrospective study was performed in order to investigate the clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia (VSB) in febrile neutropenic children in the context of the increase in incidence and antibiotic resistance of VSB. METHODS: We conducted this study among neutropenic children with underlying hematology/oncology diseases who were diagnosed with VSB at a single institution from April 2009 to June 2012. Clinical and laboratory characteristics of the children as well as antibiotic susceptibility of the causative viridans streptococci were evaluated. RESULTS: Fifty-seven episodes of VSB were diagnosed in 50 children. Severe complications occurred in four children (7.0%), and a death of one child (1.8%) was attributable to VSB. Acute myeloid leukemia was the most common underlying disease (70.2% of all cases), and 71.9% of all cases received chemotherapy including high-dose cytarabine. VSB occurred at a median of 13 days (range 8-21 days) after the beginning of chemotherapy, and fever lasted for a median of 4 days (range 1-21 days). The C-reactive protein level significantly increased within a week after the occurrence of VSB (p < 0.001) and the maximum C-reactive protein level showed a positive correlation with fever duration (r = 0.362, p = 0.007). Second blood cultures were done before the use of glycopeptides in 33 children, and negative results were observed in 30 children (90.9%). Susceptibilities to cefotaxime, cefepime, and vancomycin were 58.9, 69.1, and 100%, respectively. CONCLUSIONS: Severe complications of VSB in neutropenic febrile children were rare. We suggest glycopeptide use according to the results of blood culture and antibiotic susceptibility tests based on the susceptibility to cefepime and the microbiologic response to empirical antibiotic treatment not including glycopeptides in this study.