Pertussis is well controlled in the United States by routine childhood immunization. In contrast,... more Pertussis is well controlled in the United States by routine childhood immunization. In contrast, this disease is endemic and epidemic in Germany because routine immunization has not been implemented. To gain information relating to the epidemiology of Bordetella pertussis infections, we examined the prevalence and magnitude of B. pertussis agglutinins and of IgG and IgA antibodies (detected by enzyme-linked immunosorbent assay) to four B. pertussis antigens--lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in the sera of 119 American university students and 119 German military recruits of similar age. Geometric mean titers of agglutinins and geometric mean values for IgG antibodies to the four antigens were two- to threefold higher in sera from the American students than in sera from German recruits. In contrast, the geometric mean IgA values and the percentage of subjects with detectable IgA antibodies to the four antigens were similar in the two populations. Since IgA antibody results mainly from infection and not from immunization, our data suggest that B. pertussis infections are common among both American and German young adults despite the marked difference in rates of clinical pertussis in the two countries.
Iron is an essential micronutrient for most microbes and their hosts. Mammalian hosts respond to ... more Iron is an essential micronutrient for most microbes and their hosts. Mammalian hosts respond to infection by inducing the iron-regulatory hormone hepcidin, which causes iron sequestration and a rapid decrease in the plasma and extracellular iron concentration (hypoferremia). Previous studies showed that hepcidin regulation of iron is essential for protection from infection-associated mortality with the siderophilic pathogens Yersinia enterocolitica and Vibrio vulnificus. However, the evolutionary conservation of the hypoferremic response to infection suggests that not only rare siderophilic bacteria but also common pathogens may be targeted by this mechanism. We tested 10 clinical isolates of Escherichia coli from children with sepsis and found that both genetic iron overload (by hepcidin-1 knockout [HKO]) and iatrogenic iron overload (by intravenous iron) potentiated infection with 8 out of the 10 studied isolates: after peritoneal injection of E. coli, iron-loaded mice developed sepsis with 60% to 100% mortality within 24 h, while control wild-type mice suffered 0% mortality. Using one strain for more detailed study, we show that iron overload allows rapid bacterial multiplication and dissemination. We further found that the presence of non-transferrin-bound iron (NTBI) in the circulation is more important than total plasma or tissue iron in rendering mice susceptible to infection and mortality. Postinfection treatment of HKO mice with just two doses of the hepcidin agonist PR73 abolished NTBI and completely prevented sepsisassociated mortality. We demonstrate that the siderophilic phenotype extends to clinically common pathogens. The use of hepcidin agonists promises to be an effective early intervention in patients with infections and dysregulated iron metabolism.
A 5 year old boy with end-stage renal disease presented with clinical and laboratory findings of ... more A 5 year old boy with end-stage renal disease presented with clinical and laboratory findings of peritonitis. Peritoneal fluid revealed infection with Leclercia adecarboxylata. This is a motile, gram-negative bacillus, formerly designated enteric group 41 and Escherichia adecarboxylata. To our knowledge, this is the first reported case of peritonitis due to this organism.
This chapter on pediatric infectious diseases first presents patient scenarios, followed by a que... more This chapter on pediatric infectious diseases first presents patient scenarios, followed by a question-and-answer format to provide active learning to emphasize key points regarding clinically relevant topics, which are also covered in the American Board of Pediatrics Content Outline for certification exams. The topics addressed in this chapter range from common infectious processes encountered by pediatricians to more unusual, but important, conditions. Specific topics include infections in immunocompromised hosts, sepsis, central nervous system infections, respiratory infections, gastrointestinal infections, hepatitis, bone and joint infections, regional mycoses, parasites, sexually transmitted infections, infections in neonates, management of antimicrobial agents, pediatric HIV-1, and immunizations.
Table 1b. Therapeutic Drug Monitoring of CAZ-AVI concentrations in CSF and Human Plasma (HP) pert... more Table 1b. Therapeutic Drug Monitoring of CAZ-AVI concentrations in CSF and Human Plasma (HP) pertaining to patient 2 and 3 Conclusion. Measuring CZA concentration levels in CSF was achieved in 3 patients with complicated CNS infections. Post-infusion concentrations indicated that adequate CAZ and AVI exposures were attained in the CSF. Notably, avibactam was shown to achieve concentrations ≥1 µg/ml in the CSF throughout the dosing interval. For avibactam and ceftazidime, the PK/PD target correlated with bacterial killing is ~50% fT >MIC. In 2 out of 3 patients, concentrations were determined to be above the respective MICs throughout the entire dosing interval in the CSF. All patients attained clinical and microbiological cure. A novel CZA TDM method was successfully employed to establish that CZA maintains therapeutic CSF concentrations that exceed the MIC throughout the dosing interval.
Prematurity and low birthweight are seen frequently in infants with human immunodeficiency virus ... more Prematurity and low birthweight are seen frequently in infants with human immunodeficiency virus (HIV) type 1 infection, adding significant comorbidities and complicating the approach to treatment. HIV disease progression accelerates in the setting of an immature immune system. Recent cases have underscored the unique opportunity to not only limit progression, but also limit the establishment of HIV reservoirs that impede viral clearance by starting antiretroviral treatment (ART) early in the neonatal period. Although pediatric ART alternatives are increasing, there are still only few available agents for the treatment of neonates, especially premature and low-birthweight infants. Zidovudine is the only agent for which there is sufficient experience in premature infants, while being an intravenous alternative for infants in whom enteric administration is not possible. Nevirapine has been studied for prophylactic dosing in preterm infants. It is imperative that resources are devoted to the study of the safety and efficacy of ARTs for use during the neonatal period.
Viral hepatitis is one of the leading causes of disease around the world. In Latin America is a s... more Viral hepatitis is one of the leading causes of disease around the world. In Latin America is a severe public health problem. We conducted a case-control study in the Cayetano Heredia Hospital, Lima, Perú, seeking for risk factors for hepatitis B infection. We found 0.41% of frequency of HBsAg and 8.13% of anti-HBs in the 492 persons screened. Contact with blood was confirmed as a risk factor for hepatitis B infection; disposable needle-wash was also identified as a major risk factor. The personnel of the Sterilization Room is also in high risk for the infection. The nurse-aid personnel was also identified as a high-risk group. We suggest that the needle wash is a risk factor very easy to remove, and also stopping the rotation of the auxiliary personnel could reduce the incidence of the infection in the personnel at risk.
Methods: To improve C difficile testing, a new 2-tier algorithm was implemented in 2019 starting ... more Methods: To improve C difficile testing, a new 2-tier algorithm was implemented in 2019 starting with PCR testing. An indeterminate result was defined as a sample with a positive PCR and a positive Glutamate Dehydrogenase (GDH)/negative toxin result or a positive PCR and a negative GDH/positive toxin result. Indeterminate results were classified by episode severity and number. Patient records were reviewed by the Antimicrobial Stewardship (AS) physician and pharmacist to determine true infection versus colonization. Treatment was given as per recent IDSA Guidelines. All patients with indeterminate results were followed for 90 days for development of infection or hospitalization due to C difficile. Adults with stool samples submitted for testing between 6/1/2019 and 12/31/2019 were included. A total of 169 specimens were reviewed: 75 were positive, 72 were indeterminate (4 excluded from final analysis) and 22 were negative. Results: Using a 2-tier testing algorithm, 68 (41%) of all results were indeterminate. Our AS classified 47 (69%) of those as infection and 21 (31%) as colonization. Patients with indeterminate results who were treated had a low incidence (8.5%) of reinfection requiring hospitalization in the following 90 days. There were no hospitalizations in the untreated group. Of patients with an indeterminate result who were treated, 42 (89%) were categorized as an initial episode of C difficile infection. Conclusion: Clinical correlation of indeterminate results is critical to algorithm interpretation. A combined approach with provider education, an electronic testing advisor, a 2-tier testing algorithm, daily monitoring and prescribing by the AS team resulted in favorable outcomes for patients with indeterminate results Disclosures: All Authors: No reported disclosures 101. Diagnostic Utility of a Multiplex PCR Meningitis/Encephalitis Panel and Impact on Antibiotic Use
To measure cerebral metabolite levels in perinatally HIV-infected youths and healthy controls usi... more To measure cerebral metabolite levels in perinatally HIV-infected youths and healthy controls using the accelerated five dimensional (5D) echo planar J-resolved spectroscopic imaging (EP-JRESI) sequence, which is capable of obtaining two dimensional (2D) Jresolved spectra from three spatial dimensions (3D).
Journal of Antimicrobial Chemotherapy, Aug 12, 2010
by oral fluconazole for an additional 10 days with good response. A CT scan performed after 20 da... more by oral fluconazole for an additional 10 days with good response. A CT scan performed after 20 days demonstrated resolution of pulmonary lesions. The 6 month follow-up was negative. Candida pneumonia is an extremely rare disease, associated with high mortality rates. A pulmonary infection caused by Candida spp. may exist in two forms: a very rare primary pneumonia due to aspiration of oropharyngeal material; and a relatively more common secondary pneumonia due to haematogenous seeding from a distant site of infection. The predominant origins of septic pulmonary embolism due to Candida spp. are right-sided fungal endocarditis, CVC infection, central venous thrombophlebitis and drug addiction. 2 The presence of Candida in respiratory specimens may be due to contamination and there are no specific clinical and radiological pictures. The clinical syndrome is usually dominated by signs and symptoms of systemic inflammatory syndrome, 3 while the radiographic features include a miliary nodular pattern, with feeding-vessel sign, ground-glass opacity, small nodules or multiple larger nodules with ill-defined borders randomly distributed in bilateral lungs. This pattern was prevalent in the two patients presented here. Other less common CT findings include airspace consolidation, pleural effusion, cavitation and thickening of the bronchial walls. 4 Conclusive diagnosis requires demonstration of the organism in lung tissues. Our two cases were not confirmed by biopsy but certain points strongly favoured the diagnosis: (i) the patients were immunocompromised; (ii) Candida spp. were repeatedly isolated from bronchial samples; (iii) tracheal and bronchial specimen cultures and blood cultures were negative for pyogenic organisms; (iv) PAC cultures were positive for Candida spp; (v) patients failed to respond to ordinary antibiotics; and (vi) there was a good clinical as well as radiological response to antifungal therapy. To date, this is the first report of pulmonary candidiasis treated with anidulafungin therapy. Recently, Crandon et al. 5 studied the bronchopulmonary penetration of intravenous voriconazole and anidulafungin given in combination in healthy adults, and found good anidulafungin concentrations in alveolar macrophages and optimal lung distribution. Another study found the combination of anidulafungin and voriconazole synergistic at a dosage of 5 mg/kg/day in neutropenic rabbits with experimental invasive pulmonary aspergillosis. 6 These data seem to support the clinical use of this drug alone or in combination with voriconazole for the treatment of Candida lung infections. In conclusion, we have described two cases of bilateral septic pulmonary candidiasis successfully treated with anidulafungin therapy. This report suggests a potential role for anidulafungin in the treatment of pulmonary fungal infections. Funding M. F. was supported in this study by a grant from the Faculty of Medicine of the University of Rome 'La Sapienza'. Data have been generated as part of routine hospital work. Transparency declarations M. F. was on the speakers' bureau for Pfizer, Novartis and Merck. M. V. was on the speakers' bureau for Pfizer,
Human immunodeficiency virus type 1 (HIV-1) infected children treated with highly active antiretr... more Human immunodeficiency virus type 1 (HIV-1) infected children treated with highly active antiretroviral therapy (HAART) may develop a significant reduction of plasma viremia associated with an increase in CD4+ T-cell counts. Functional capacity of this reconstituted immune system in response to recall antigens is important to maintain protective immunity to vaccine-preventable diseases. We therefore determined cellular and humoral immune responses to tetanus toxoid (TT) booster in perinatally HIV-1-infected children and adolescents receiving HAART. Immune responses were prospectively evaluated pre- and post-tetanus booster using lymphocyte proliferation assay (LPA) stimulation index (SI > or = 3.0) and tetanus antibody (TAb > or = 0.15) in 15 patients. The median interval from primary tetanus immunization series was 6 years (range 2-12 years). We compared patients by their virological response to HAART (complete responders, CR, n=7; incomplete responders, ICR, n=8). There were no significant differences in median age 12.6 years (CR: 12.9; ICR: 10.6) or median CD4 T-cell pre-booster (CR: 35%/819; ICR: 26%/429) between groups. Tetanus LPA responses were observed in one patient prior to booster and in seven patients post-booster. In contrast, 38% of patients had protective TAb pre-booster, but 92% developed protective TAb post-booster. All of the CR and 5/6 ICR patients developed protective TAb. HIV-1-infected children and adolescents had modest LPA responses to tetanus following booster, similar to HIV-1-infected adults. However, the majority of patients developed protective TAb levels after booster and maintained the response. Shorter intervals may need to be considered for TT immunization boosters in HIV-1-infected pediatric patients, as only 38% had protective TAb at baseline.
in vitro susceptibility to fl uconazole MIC of 64 mg/l, suggesting some strains of A. pullulans m... more in vitro susceptibility to fl uconazole MIC of 64 mg/l, suggesting some strains of A. pullulans may be resistant to fl uconazole. Case report An 11-year-old boy with a history of intestinal lymphangiectasia, protein losing enteropathy and lymphopenia presented with a 1-day history of fever of up to 40.1 ° C and chills. Due to his total parenteral nutrition-dependency, he had a Hickman catheter which had been originally placed 7 months prior to his admission. His catheter site was without erythema, warmth or discharge. He was admitted with suspected intravascular catheter-related bloodstream infection and started empirically on vancomycin, piperacillin-tazobactam, and gentamicin. After 30 h of incubation, one aerobic BacT/Alert bottle (bioM é rieux, Marcy l ' Etoile, France) and one fungal BACTEC bottle (BD, Franklin Lakes, New Jersey) inoculated with samples from his Hickman catheter yielded yeast-like organisms which were visualized by wet mount and Calcofl uor (Polysciences, Inc., Warrington, Pennsylvania) staining. The same organism was recovered after 11 days of incubation from a fungal BACTEC blood culture bottle
Background This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, a... more Background This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion. Methods RSV-seronegative children aged 6–24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season. Results Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96...
A 7-year-old cystic fibrosis patient with increased cough, new pulmonary infiltrate, and declinin... more A 7-year-old cystic fibrosis patient with increased cough, new pulmonary infiltrate, and declining pulmonary function was diagnosed with clarithromycin resistant Mycobacterium abscessus infection. Treatment was initiated with clofazimine, linezolid and cefoxitin; she responded well to therapy and achieved microbiological clearance after completion of 12-month treatment. One year later, she had re-emergence of worsening symptoms and her sputum culture again grew clarithromycin resistant M. abscessus. Using a laboratory developed whole genome sequencing (WGS) test, the bacterium was determined to be the same strain with the same resistance mechanisms, indicating a relapse. This was deemed a critical element of clinical information, as the isolation of a genetically distinct organism would have indicated a new infection and would have served as evidence that a 12-month regimen was likely sufficient to achieve eradication. The confirmation of a relapse prompted the prolongation of the therapy plan to a goal of 24 months. Reinfection and relapse are great challenges in patients with cystic fibrosis who may acquire new strain of M. abscessus from the environment, may harbor multiple subpopulations of bacteria, or may have persistent infections but intermittent bacteria shedding that could not be eradicated. WGS has emerged as a powerful molecular tool to accurately differentiate re-infection from relapse thus solving this conundrum.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2022
Background: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic ... more Background: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV. Methods: IMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6–12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5–9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant. Results: Twenty-nin...
Pertussis is well controlled in the United States by routine childhood immunization. In contrast,... more Pertussis is well controlled in the United States by routine childhood immunization. In contrast, this disease is endemic and epidemic in Germany because routine immunization has not been implemented. To gain information relating to the epidemiology of Bordetella pertussis infections, we examined the prevalence and magnitude of B. pertussis agglutinins and of IgG and IgA antibodies (detected by enzyme-linked immunosorbent assay) to four B. pertussis antigens--lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in the sera of 119 American university students and 119 German military recruits of similar age. Geometric mean titers of agglutinins and geometric mean values for IgG antibodies to the four antigens were two- to threefold higher in sera from the American students than in sera from German recruits. In contrast, the geometric mean IgA values and the percentage of subjects with detectable IgA antibodies to the four antigens were similar in the two populations. Since IgA antibody results mainly from infection and not from immunization, our data suggest that B. pertussis infections are common among both American and German young adults despite the marked difference in rates of clinical pertussis in the two countries.
Iron is an essential micronutrient for most microbes and their hosts. Mammalian hosts respond to ... more Iron is an essential micronutrient for most microbes and their hosts. Mammalian hosts respond to infection by inducing the iron-regulatory hormone hepcidin, which causes iron sequestration and a rapid decrease in the plasma and extracellular iron concentration (hypoferremia). Previous studies showed that hepcidin regulation of iron is essential for protection from infection-associated mortality with the siderophilic pathogens Yersinia enterocolitica and Vibrio vulnificus. However, the evolutionary conservation of the hypoferremic response to infection suggests that not only rare siderophilic bacteria but also common pathogens may be targeted by this mechanism. We tested 10 clinical isolates of Escherichia coli from children with sepsis and found that both genetic iron overload (by hepcidin-1 knockout [HKO]) and iatrogenic iron overload (by intravenous iron) potentiated infection with 8 out of the 10 studied isolates: after peritoneal injection of E. coli, iron-loaded mice developed sepsis with 60% to 100% mortality within 24 h, while control wild-type mice suffered 0% mortality. Using one strain for more detailed study, we show that iron overload allows rapid bacterial multiplication and dissemination. We further found that the presence of non-transferrin-bound iron (NTBI) in the circulation is more important than total plasma or tissue iron in rendering mice susceptible to infection and mortality. Postinfection treatment of HKO mice with just two doses of the hepcidin agonist PR73 abolished NTBI and completely prevented sepsisassociated mortality. We demonstrate that the siderophilic phenotype extends to clinically common pathogens. The use of hepcidin agonists promises to be an effective early intervention in patients with infections and dysregulated iron metabolism.
A 5 year old boy with end-stage renal disease presented with clinical and laboratory findings of ... more A 5 year old boy with end-stage renal disease presented with clinical and laboratory findings of peritonitis. Peritoneal fluid revealed infection with Leclercia adecarboxylata. This is a motile, gram-negative bacillus, formerly designated enteric group 41 and Escherichia adecarboxylata. To our knowledge, this is the first reported case of peritonitis due to this organism.
This chapter on pediatric infectious diseases first presents patient scenarios, followed by a que... more This chapter on pediatric infectious diseases first presents patient scenarios, followed by a question-and-answer format to provide active learning to emphasize key points regarding clinically relevant topics, which are also covered in the American Board of Pediatrics Content Outline for certification exams. The topics addressed in this chapter range from common infectious processes encountered by pediatricians to more unusual, but important, conditions. Specific topics include infections in immunocompromised hosts, sepsis, central nervous system infections, respiratory infections, gastrointestinal infections, hepatitis, bone and joint infections, regional mycoses, parasites, sexually transmitted infections, infections in neonates, management of antimicrobial agents, pediatric HIV-1, and immunizations.
Table 1b. Therapeutic Drug Monitoring of CAZ-AVI concentrations in CSF and Human Plasma (HP) pert... more Table 1b. Therapeutic Drug Monitoring of CAZ-AVI concentrations in CSF and Human Plasma (HP) pertaining to patient 2 and 3 Conclusion. Measuring CZA concentration levels in CSF was achieved in 3 patients with complicated CNS infections. Post-infusion concentrations indicated that adequate CAZ and AVI exposures were attained in the CSF. Notably, avibactam was shown to achieve concentrations ≥1 µg/ml in the CSF throughout the dosing interval. For avibactam and ceftazidime, the PK/PD target correlated with bacterial killing is ~50% fT >MIC. In 2 out of 3 patients, concentrations were determined to be above the respective MICs throughout the entire dosing interval in the CSF. All patients attained clinical and microbiological cure. A novel CZA TDM method was successfully employed to establish that CZA maintains therapeutic CSF concentrations that exceed the MIC throughout the dosing interval.
Prematurity and low birthweight are seen frequently in infants with human immunodeficiency virus ... more Prematurity and low birthweight are seen frequently in infants with human immunodeficiency virus (HIV) type 1 infection, adding significant comorbidities and complicating the approach to treatment. HIV disease progression accelerates in the setting of an immature immune system. Recent cases have underscored the unique opportunity to not only limit progression, but also limit the establishment of HIV reservoirs that impede viral clearance by starting antiretroviral treatment (ART) early in the neonatal period. Although pediatric ART alternatives are increasing, there are still only few available agents for the treatment of neonates, especially premature and low-birthweight infants. Zidovudine is the only agent for which there is sufficient experience in premature infants, while being an intravenous alternative for infants in whom enteric administration is not possible. Nevirapine has been studied for prophylactic dosing in preterm infants. It is imperative that resources are devoted to the study of the safety and efficacy of ARTs for use during the neonatal period.
Viral hepatitis is one of the leading causes of disease around the world. In Latin America is a s... more Viral hepatitis is one of the leading causes of disease around the world. In Latin America is a severe public health problem. We conducted a case-control study in the Cayetano Heredia Hospital, Lima, Perú, seeking for risk factors for hepatitis B infection. We found 0.41% of frequency of HBsAg and 8.13% of anti-HBs in the 492 persons screened. Contact with blood was confirmed as a risk factor for hepatitis B infection; disposable needle-wash was also identified as a major risk factor. The personnel of the Sterilization Room is also in high risk for the infection. The nurse-aid personnel was also identified as a high-risk group. We suggest that the needle wash is a risk factor very easy to remove, and also stopping the rotation of the auxiliary personnel could reduce the incidence of the infection in the personnel at risk.
Methods: To improve C difficile testing, a new 2-tier algorithm was implemented in 2019 starting ... more Methods: To improve C difficile testing, a new 2-tier algorithm was implemented in 2019 starting with PCR testing. An indeterminate result was defined as a sample with a positive PCR and a positive Glutamate Dehydrogenase (GDH)/negative toxin result or a positive PCR and a negative GDH/positive toxin result. Indeterminate results were classified by episode severity and number. Patient records were reviewed by the Antimicrobial Stewardship (AS) physician and pharmacist to determine true infection versus colonization. Treatment was given as per recent IDSA Guidelines. All patients with indeterminate results were followed for 90 days for development of infection or hospitalization due to C difficile. Adults with stool samples submitted for testing between 6/1/2019 and 12/31/2019 were included. A total of 169 specimens were reviewed: 75 were positive, 72 were indeterminate (4 excluded from final analysis) and 22 were negative. Results: Using a 2-tier testing algorithm, 68 (41%) of all results were indeterminate. Our AS classified 47 (69%) of those as infection and 21 (31%) as colonization. Patients with indeterminate results who were treated had a low incidence (8.5%) of reinfection requiring hospitalization in the following 90 days. There were no hospitalizations in the untreated group. Of patients with an indeterminate result who were treated, 42 (89%) were categorized as an initial episode of C difficile infection. Conclusion: Clinical correlation of indeterminate results is critical to algorithm interpretation. A combined approach with provider education, an electronic testing advisor, a 2-tier testing algorithm, daily monitoring and prescribing by the AS team resulted in favorable outcomes for patients with indeterminate results Disclosures: All Authors: No reported disclosures 101. Diagnostic Utility of a Multiplex PCR Meningitis/Encephalitis Panel and Impact on Antibiotic Use
To measure cerebral metabolite levels in perinatally HIV-infected youths and healthy controls usi... more To measure cerebral metabolite levels in perinatally HIV-infected youths and healthy controls using the accelerated five dimensional (5D) echo planar J-resolved spectroscopic imaging (EP-JRESI) sequence, which is capable of obtaining two dimensional (2D) Jresolved spectra from three spatial dimensions (3D).
Journal of Antimicrobial Chemotherapy, Aug 12, 2010
by oral fluconazole for an additional 10 days with good response. A CT scan performed after 20 da... more by oral fluconazole for an additional 10 days with good response. A CT scan performed after 20 days demonstrated resolution of pulmonary lesions. The 6 month follow-up was negative. Candida pneumonia is an extremely rare disease, associated with high mortality rates. A pulmonary infection caused by Candida spp. may exist in two forms: a very rare primary pneumonia due to aspiration of oropharyngeal material; and a relatively more common secondary pneumonia due to haematogenous seeding from a distant site of infection. The predominant origins of septic pulmonary embolism due to Candida spp. are right-sided fungal endocarditis, CVC infection, central venous thrombophlebitis and drug addiction. 2 The presence of Candida in respiratory specimens may be due to contamination and there are no specific clinical and radiological pictures. The clinical syndrome is usually dominated by signs and symptoms of systemic inflammatory syndrome, 3 while the radiographic features include a miliary nodular pattern, with feeding-vessel sign, ground-glass opacity, small nodules or multiple larger nodules with ill-defined borders randomly distributed in bilateral lungs. This pattern was prevalent in the two patients presented here. Other less common CT findings include airspace consolidation, pleural effusion, cavitation and thickening of the bronchial walls. 4 Conclusive diagnosis requires demonstration of the organism in lung tissues. Our two cases were not confirmed by biopsy but certain points strongly favoured the diagnosis: (i) the patients were immunocompromised; (ii) Candida spp. were repeatedly isolated from bronchial samples; (iii) tracheal and bronchial specimen cultures and blood cultures were negative for pyogenic organisms; (iv) PAC cultures were positive for Candida spp; (v) patients failed to respond to ordinary antibiotics; and (vi) there was a good clinical as well as radiological response to antifungal therapy. To date, this is the first report of pulmonary candidiasis treated with anidulafungin therapy. Recently, Crandon et al. 5 studied the bronchopulmonary penetration of intravenous voriconazole and anidulafungin given in combination in healthy adults, and found good anidulafungin concentrations in alveolar macrophages and optimal lung distribution. Another study found the combination of anidulafungin and voriconazole synergistic at a dosage of 5 mg/kg/day in neutropenic rabbits with experimental invasive pulmonary aspergillosis. 6 These data seem to support the clinical use of this drug alone or in combination with voriconazole for the treatment of Candida lung infections. In conclusion, we have described two cases of bilateral septic pulmonary candidiasis successfully treated with anidulafungin therapy. This report suggests a potential role for anidulafungin in the treatment of pulmonary fungal infections. Funding M. F. was supported in this study by a grant from the Faculty of Medicine of the University of Rome 'La Sapienza'. Data have been generated as part of routine hospital work. Transparency declarations M. F. was on the speakers' bureau for Pfizer, Novartis and Merck. M. V. was on the speakers' bureau for Pfizer,
Human immunodeficiency virus type 1 (HIV-1) infected children treated with highly active antiretr... more Human immunodeficiency virus type 1 (HIV-1) infected children treated with highly active antiretroviral therapy (HAART) may develop a significant reduction of plasma viremia associated with an increase in CD4+ T-cell counts. Functional capacity of this reconstituted immune system in response to recall antigens is important to maintain protective immunity to vaccine-preventable diseases. We therefore determined cellular and humoral immune responses to tetanus toxoid (TT) booster in perinatally HIV-1-infected children and adolescents receiving HAART. Immune responses were prospectively evaluated pre- and post-tetanus booster using lymphocyte proliferation assay (LPA) stimulation index (SI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 3.0) and tetanus antibody (TAb &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 0.15) in 15 patients. The median interval from primary tetanus immunization series was 6 years (range 2-12 years). We compared patients by their virological response to HAART (complete responders, CR, n=7; incomplete responders, ICR, n=8). There were no significant differences in median age 12.6 years (CR: 12.9; ICR: 10.6) or median CD4 T-cell pre-booster (CR: 35%/819; ICR: 26%/429) between groups. Tetanus LPA responses were observed in one patient prior to booster and in seven patients post-booster. In contrast, 38% of patients had protective TAb pre-booster, but 92% developed protective TAb post-booster. All of the CR and 5/6 ICR patients developed protective TAb. HIV-1-infected children and adolescents had modest LPA responses to tetanus following booster, similar to HIV-1-infected adults. However, the majority of patients developed protective TAb levels after booster and maintained the response. Shorter intervals may need to be considered for TT immunization boosters in HIV-1-infected pediatric patients, as only 38% had protective TAb at baseline.
in vitro susceptibility to fl uconazole MIC of 64 mg/l, suggesting some strains of A. pullulans m... more in vitro susceptibility to fl uconazole MIC of 64 mg/l, suggesting some strains of A. pullulans may be resistant to fl uconazole. Case report An 11-year-old boy with a history of intestinal lymphangiectasia, protein losing enteropathy and lymphopenia presented with a 1-day history of fever of up to 40.1 ° C and chills. Due to his total parenteral nutrition-dependency, he had a Hickman catheter which had been originally placed 7 months prior to his admission. His catheter site was without erythema, warmth or discharge. He was admitted with suspected intravascular catheter-related bloodstream infection and started empirically on vancomycin, piperacillin-tazobactam, and gentamicin. After 30 h of incubation, one aerobic BacT/Alert bottle (bioM é rieux, Marcy l ' Etoile, France) and one fungal BACTEC bottle (BD, Franklin Lakes, New Jersey) inoculated with samples from his Hickman catheter yielded yeast-like organisms which were visualized by wet mount and Calcofl uor (Polysciences, Inc., Warrington, Pennsylvania) staining. The same organism was recovered after 11 days of incubation from a fungal BACTEC blood culture bottle
Background This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, a... more Background This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion. Methods RSV-seronegative children aged 6–24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season. Results Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96...
A 7-year-old cystic fibrosis patient with increased cough, new pulmonary infiltrate, and declinin... more A 7-year-old cystic fibrosis patient with increased cough, new pulmonary infiltrate, and declining pulmonary function was diagnosed with clarithromycin resistant Mycobacterium abscessus infection. Treatment was initiated with clofazimine, linezolid and cefoxitin; she responded well to therapy and achieved microbiological clearance after completion of 12-month treatment. One year later, she had re-emergence of worsening symptoms and her sputum culture again grew clarithromycin resistant M. abscessus. Using a laboratory developed whole genome sequencing (WGS) test, the bacterium was determined to be the same strain with the same resistance mechanisms, indicating a relapse. This was deemed a critical element of clinical information, as the isolation of a genetically distinct organism would have indicated a new infection and would have served as evidence that a 12-month regimen was likely sufficient to achieve eradication. The confirmation of a relapse prompted the prolongation of the therapy plan to a goal of 24 months. Reinfection and relapse are great challenges in patients with cystic fibrosis who may acquire new strain of M. abscessus from the environment, may harbor multiple subpopulations of bacteria, or may have persistent infections but intermittent bacteria shedding that could not be eradicated. WGS has emerged as a powerful molecular tool to accurately differentiate re-infection from relapse thus solving this conundrum.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2022
Background: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic ... more Background: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV. Methods: IMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6–12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5–9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant. Results: Twenty-nin...
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Papers by Jaime Deville