Browsing by Author "Carugati, Manuela"
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Item Open Access A prospective study of Escherichia coli bloodstream infection among adolescents and adults in northern Tanzania.(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2020-05) Madut, Deng B; Rubach, Matthew P; Kalengo, Nathaniel; Carugati, Manuela; Maze, Michael J; Morrissey, Anne B; Mmbaga, Blandina T; Lwezaula, Bingileki F; Kilonzo, Kajiru G; Maro, Venance P; Crump, John ABackground
Characterization of the epidemiology of Escherichia coli bloodstream infection (BSI) in sub-Saharan Africa is lacking. We studied patients with E. coli BSI in northern Tanzania to describe host risk factors for infection and to describe the antimicrobial susceptibility of isolates.Methods
Within 24 h of admission, patients presenting with a fever at two hospitals in Moshi, Tanzania, were screened and enrolled. Cases were patients with at least one blood culture yielding E. coli and controls were those without E. coli isolated from any blood culture. Logistic regression was used to identify host risk factors for E. coli BSI.Results
We analyzed data from 33 cases and 1615 controls enrolled from 2007 through 2018. The median (IQR) age of cases was 47 (34-57) y and 24 (72.7%) were female. E. coli BSI was associated with (adjusted OR [aOR], 95% CI) increasing years of age (1.03, 1.01 to 1.05), female gender (2.20, 1.01 to 4.80), abdominal tenderness (2.24, 1.06 to 4.72) and urinary tract infection as a discharge diagnosis (3.71, 1.61 to 8.52). Of 31 isolates with antimicrobial susceptibility results, the prevalence of resistance was ampicillin 29 (93.6%), ceftriaxone three (9.7%), ciprofloxacin five (16.1%), gentamicin seven (22.6%) and trimethoprim-sulfamethoxazole 31 (100.0%).Conclusions
In Tanzania, host risk factors for E. coli BSI were similar to those reported in high-resource settings and resistance to key antimicrobials was common.Item Open Access Antibacterial Utilization for Febrile Illnesses and Laboratory-Confirmed Bloodstream Infections in Northern Tanzania.(Open forum infectious diseases, 2023-08) Moorthy, Ganga S; Madut, Deng B; Kilonzo, Kajiru G; Lwezaula, Bingileki F; Mbwasi, Ronald; Mmbaga, Blandina T; Ngocho, James S; Saganda, Wilbrod; Bonnewell, John P; Carugati, Manuela; Egger, Joseph R; Hertz, Julian T; Tillekeratne, L Gayani; Maze, Michael J; Maro, Venance P; Crump, John A; Rubach, Matthew PBackground
We describe antibacterial use in light of microbiology data and treatment guidelines for common febrile syndromes in Moshi, Tanzania.Methods
We compared data from 2 hospital-based prospective cohort studies, cohort 1 (2011-2014) and cohort 2 (2016-2019), that enrolled febrile children and adults. A study team member administered a standardized questionnaire, performed a physical examination, and collected blood cultures. Participants with bloodstream infection (BSI) were categorized as receiving effective or ineffective therapy based upon antimicrobial susceptibility interpretations. Antibacterials prescribed for treatment of pneumonia, urinary tract infection (UTI), or presumed sepsis were compared with World Health Organization and Tanzania Standard Treatment Guidelines. We used descriptive statistics and logistic regression to describe antibacterial use.Results
Among participants, 430 of 1043 (41.2%) and 501 of 1132 (44.3%) reported antibacterial use prior to admission in cohorts 1 and 2, respectively. During admission, 930 of 1043 (89.2%) received antibacterials in cohort 1 and 1060 of 1132 (93.6%) in cohort 2. Inpatient use of ceftriaxone, metronidazole, and ampicillin increased between cohorts (P ≤ .002 for each). BSI was detected in 38 (3.6%) participants in cohort 1 and 47 (4.2%) in cohort 2. Of 85 participants with BSI, 81 (95.3%) had complete data and 52 (64.2%) were prescribed effective antibacterials. Guideline-consistent therapy in cohort 1 and cohort 2 was as follows: pneumonia, 87.4% and 56.8%; UTI, 87.6% and 69.0%; sepsis, 84.4% and 61.2% (P ≤ .001 for each).Conclusions
Receipt of antibacterials for febrile illness was common. While guideline-consistent prescribing increased over time, more than one-third of participants with BSI received ineffective antibacterials.Item Open Access Autochthonous ST405 NDM-5 producing Escherichia coli causing fatal sepsis in Northern Italy.(International journal of antimicrobial agents, 2020-05) Peri, Anna Maria; Piazza, Aurora; De Zan, Valentina; Carugati, Manuela; Muscatello, Antonio; Comandatore, Francesco; De Lorenzis, Elisa; Pluderi, Mauro; Arghittu, Milena; Cariani, Lisa; Cantù, Anna Paola; Bandi, Claudio; Cugno, Massimo; Gori, Andrea; Bandera, AlessandraItem Open Access Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study.(European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2020-08) Carugati, Manuela; Aliberti, S; Sotgiu, G; Blasi, F; Gori, A; Menendez, R; Encheva, M; Gallego, M; Leuschner, P; Ruiz-Buitrago, S; Battaglia, S; Fantini, R; Pascual-Guardia, S; Marin-Corral, J; Restrepo, MI; GLIMP CollaboratorsAn accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients.Item Open Access Challenges in the Diagnosis and Management of Bacterial Lung Infections in Solid Organ Recipients: A Narrative Review.(International journal of molecular sciences, 2020-02) Carugati, Manuela; Morlacchi, Letizia Corinna; Peri, Anna Maria; Alagna, Laura; Rossetti, Valeria; Bandera, Alessandra; Gori, Andrea; Blasi, Francesco; Working Group, IfaltRespiratory infections pose a significant threat to the success of solid organ transplantation, and the diagnosis and management of these infections are challenging. The current narrative review addressed some of these challenges, based on evidence from the literature published in the last 20 years. Specifically, we focused our attention on (i) the obstacles to an etiologic diagnosis of respiratory infections among solid organ transplant recipients, (ii) the management of bacterial respiratory infections in an era characterized by increased antimicrobial resistance, and (iii) the development of antimicrobial stewardship programs dedicated to solid organ transplant recipients.Item Open Access Correction to: Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study.(European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2021-09) Carugati, Manuela; Aliberti, S; Sotgiu, G; Blasi, F; Gori, A; Menendez, R; Encheva, M; Gallego, M; Leuschner, P; Ruiz-Buitrago, S; Battaglia, S; Fantini, R; Pascual-Guardia, S; Marin-Corral, J; Restrepo, MI; GLIMP CollaboratorsIn the originally published article, the individual collaborator names were not captured under the group name “GLIMP Collaborators”. The names are now captured correctly under this group accordingly. The original article has been corrected.Item Open Access Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.(JAMA, 2018-09) Holland, Thomas L; Raad, Issam; Boucher, Helen W; Anderson, Deverick J; Cosgrove, Sara E; Aycock, P Suzanne; Baddley, John W; Chaftari, Anne-Marie; Chow, Shein-Chung; Chu, Vivian H; Carugati, Manuela; Cook, Paul; Corey, G Ralph; Crowley, Anna Lisa; Daly, Jennifer; Gu, Jiezhun; Hachem, Ray; Horton, James; Jenkins, Timothy C; Levine, Donald; Miro, Jose M; Pericas, Juan M; Riska, Paul; Rubin, Zachary; Rupp, Mark E; Schrank, John; Sims, Matthew; Wray, Dannah; Zervos, Marcus; Fowler, Vance G; Staphylococcal Bacteremia InvestigatorsImportance
The appropriate duration of antibiotics for staphylococcal bacteremia is unknown.Objective
To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events.Design, setting, and participants
A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization.Interventions
Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care.Main outcomes and measures
Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia.Results
Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6]).Conclusions and relevance
Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm.Trial registration
ClinicalTrials.gov Identifier: NCT01191840.Item Open Access Epidemiology of surgical site infections after solid organ transplants in the period 2015-2019: A single-center retrospective cohort study.(American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2022-09) Carugati, Manuela; Arif, Sana; Sudan, Debra Lynn; Collins, Bradley Henry; Haney, John Carroll; Schroder, Jacob Niall; Reynolds, John Michael; Lewis, Sarah Stamps; Yarrington, Michael Edwards; Miller, Rachel Ann; Alexander, Barbara DudleySurgical site infections (SSI) are severe complications of solid organ transplant (SOT). This retrospective study assessed the epidemiology of and outcomes associated with invasive primary SSI (IP-SSI) occurring within 3 months of transplantation in adult SOT recipients at Duke University over a 5-year period (2015-2019). Among 2073 consecutive SOT recipients, 198 IP-SSI were identified. The IP-SSI rate declined over the period (14.4% in 2015 vs. 8.3% in 2019) and was higher among multi-organ compared with single-organ transplants (33.9% vs. 8.1%, p < .01). SOT recipients with IP-SSI had longer hospital stays than patients without SSI (30.0 vs. 17.0 days, p < .01). Transplant hospitalization (9.6% vs. 2.2%, p < .01), 6-month (11.6% vs. 3.3%, p < .01), and 1-year mortality (15.7% vs. 5.8%, p < .01) were higher in SOT recipients with IP-SSI than in those without. While Gram-positive bacteria were the most common pathogens, urogenital Mollicute and atypical Mycobacteria were identified as an unexpected cause of IP-SSI, particularly among lung transplant recipients. The median time to IP-SSI was 24.0 (IQR 13.8-48.3) days, although the time to IP-SSI varied based on organ transplanted and the causative pathogen. IP-SSI is an important and potentially modifiable complication of SOT, associated with prolonged hospitalizations and reduced survival, particularly in the lung transplant population.Item Open Access Exogenous reinfection of tuberculosis in a low-burden area.(Infection, 2015-12) Schiroli, Consuelo; Carugati, Manuela; Zanini, Fabio; Bandera, Alessandra; Bandera, Alessandra; Di Nardo Stuppino, Silvia; Monge, Elisa; Morosi, Manuela; Gori, Andrea; Matteelli, Alberto; Codecasa, Luigi; Franzetti, FabioPurpose
Recurrence of tuberculosis (TB) can be the consequence of relapse or exogenous reinfection. The study aimed to assess the factors associated with exogenous TB reinfection.Methods
Prospective cohort study based on the TB database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital (Milan, Italy). Time period: 1995-2010.Inclusion criteria
(1) ≥2 episodes of culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M. tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic regression analysis was used to assess the influence of risk factors on exogenous reinfections.Result
Of the 4682 patients with TB, 83 were included. Of these, exogenous reinfection was diagnosed in 19 (23 %). It was independently associated with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p = 0.045] and with prolonged interval between the first TB episode and its recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4 years after the first episode. The risk associated with being foreign born, extrapulmonary site of TB, and HIV infection was not statistically significant. In the relapse and re-infection cohort, one-third of the patients showed a worsened drug resistance profile during the recurrent TB episode.Conclusions
Exogenous TB reinfections have been documented in low endemic areas, such as Italy. A causal association with HIV infection could not be confirmed. Relapses and exogenous reinfections shared an augmented risk of multidrug resistance development, frequently requiring the use of second-line anti-TB regimens.Item Open Access Facility-based disease surveillance and Bayesian hierarchical modeling to estimate endemic typhoid fever incidence, Kilimanjaro Region, Tanzania, 2007-2018.(PLoS neglected tropical diseases, 2022-07-05) Cutting, Elena R; Simmons, Ryan A; Madut, Deng B; Maze, Michael J; Kalengo, Nathaniel H; Carugati, Manuela; Mbwasi, Ronald M; Kilonzo, Kajiru G; Lyamuya, Furaha; Marandu, Annette; Mosha, Calvin; Saganda, Wilbrod; Lwezaula, Bingileki F; Hertz, Julian T; Morrissey, Anne B; Turner, Elizabeth L; Mmbaga, Blandina T; Kinabo, Grace D; Maro, Venance P; Crump, John A; Rubach, Matthew PGrowing evidence suggests considerable variation in endemic typhoid fever incidence at some locations over time, yet few settings have multi-year incidence estimates to inform typhoid control measures. We sought to describe a decade of typhoid fever incidence in the Kilimanjaro Region of Tanzania. Cases of blood culture confirmed typhoid were identified among febrile patients at two sentinel hospitals during three study periods: 2007-08, 2011-14, and 2016-18. To account for under-ascertainment at sentinel facilities, we derived adjustment multipliers from healthcare utilization surveys done in the hospital catchment area. Incidence estimates and credible intervals (CrI) were derived using a Bayesian hierarchical incidence model that incorporated uncertainty of our observed typhoid fever prevalence, of healthcare seeking adjustment multipliers, and of blood culture diagnostic sensitivity. Among 3,556 total participants, 50 typhoid fever cases were identified. Of typhoid cases, 26 (52%) were male and the median (range) age was 22 (<1-60) years; 4 (8%) were aged <5 years and 10 (20%) were aged 5 to 14 years. Annual typhoid fever incidence was estimated as 61.5 (95% CrI 14.9-181.9), 6.5 (95% CrI 1.4-20.4), and 4.0 (95% CrI 0.6-13.9) per 100,000 persons in 2007-08, 2011-14, and 2016-18, respectively. There were no deaths among typhoid cases. We estimated moderate typhoid incidence (≥10 per 100 000) in 2007-08 and low (<10 per 100 000) incidence during later surveillance periods, but with overlapping credible intervals across study periods. Although consistent with falling typhoid incidence, we interpret this as showing substantial variation over the study periods. Given potential variation, multi-year surveillance may be warranted in locations making decisions about typhoid conjugate vaccine introduction and other control measures.Item Open Access Fever, bacterial zoonoses, and One Health in sub-Saharan Africa.(Clinical medicine (London, England), 2019-09) Carugati, Manuela; Kilonzo, Kajiru G; Crump, John AAlthough often underappreciated, a number of bacterial zoonoses are endemic in Africa. Of these, brucellosis, leptospirosis, Q fever, and rickettsioses are responsible for a substantial proportion of febrile illness among patients seeking hospital care. In this paper, we discuss the aetiology, epidemiology, clinical presentation, diagnosis, treatment and prevention of these bacterial zoonoses. To prevent and control bacterial zoonoses, strategies targeting both animals and humans are crucial. These may lead to better outcomes than strategies based exclusively on treatment of human infections. Such strategies are referred to as the 'One Health' approach; the collaborative effort of multiple disciplines to attain optimal health for people, animals and the environment.Item Open Access Global distribution of Leptospira serovar isolations and detections from animal host species: a systematic review and online database.(medRxiv, 2023-10-03) Hagedoorn, Nienke N; Maze, Michael J; Carugati, Manuela; Cash-Goldwasser, Shama; Allan, Kathryn J; Chen, Kevin; Cossic, Brieuc; Demeter, Elena; Gallagher, Sarah; German, Richard; Galloway, Renee L; Habuš, Josipa; Rubach, Matthew P; Shiokawa, Kanae; Sulikhan, Nadezhda; Crump, John AOBJECTIVES: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, currently data are fragmented. We aimed to systematically review the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions, and to identify geographic regions in need of study. METHODS: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterized by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. RESULTS: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n=39), Icterohaemorrhagiae (n=29), Pomona (n=28), Australis (n=25), and Ballum (n=25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. CONCLUSIONS: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.Item Open Access High-dose daptomycin therapy for left-sided infective endocarditis: a prospective study from the international collaboration on endocarditis.(Antimicrobial agents and chemotherapy, 2013-12) Carugati, Manuela; Bayer, Arnold S; Miró, Josè M; Park, Lawrence P; Guimarães, Armenio C; Skoutelis, Athanasios; Fortes, Claudio Q; Durante-Mangoni, Emanuele; Hannan, Margaret M; Nacinovich, Francisco; Fernández-Hidalgo, Nuria; Grossi, Paolo; Tan, Ru-San; Holland, Thomas; Fowler, Vance G; Corey, Ralph G; Chu, Vivian H; International Collaboration on EndocarditisThe use of daptomycin in Gram-positive left-sided infective endocarditis (IE) has significantly increased. The purpose of this study was to assess the influence of high-dose daptomycin on the outcome of left-sided IE due to Gram-positive pathogens. This was a prospective cohort study based on 1,112 cases from the International Collaboration on Endocarditis (ICE)-Plus database and the ICE-Daptomycin Substudy database from 2008 to 2010. Among patients with left-sided IE due to Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus faecalis, we compared those treated with daptomycin (cohort A) to those treated with standard-of-care (SOC) antibiotics (cohort B). The primary outcome was in-hospital mortality. Time to clearance of bacteremia, 6-month mortality, and adverse events (AEs) ascribable to daptomycin were also assessed. There were 29 and 149 patients included in cohort A and cohort B, respectively. Baseline comorbidities did not differ between the two cohorts, except for a significantly higher prevalence of diabetes and previous episodes of IE among patients treated with daptomycin. The median daptomycin dose was 9.2 mg/kg of body weight/day. Two-thirds of the patients treated with daptomycin had failed a previous antibiotic regimen. In-hospital and 6-month mortalities were similar in the two cohorts. In cohort A, median time to clearance of methicillin-resistant S. aureus (MRSA) bacteremia was 1.0 day, irrespective of daptomycin dose, representing a significantly faster bacteremia clearance compared to SOC (1.0 versus 5.0 days; P < 0.01). Regimens with higher daptomycin doses were not associated with increased incidence of AEs. In conclusion, higher-dose daptomycin may be an effective and safe alternative to SOC in the treatment of left-sided IE due to common Gram-positive pathogens.Item Open Access Incidence Estimates of Acute Q Fever and Spotted Fever Group Rickettsioses, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014.(The American journal of tropical medicine and hygiene, 2021-12) Pisharody, Sruti; Rubach, Matthew P; Carugati, Manuela; Nicholson, William L; Perniciaro, Jamie L; Biggs, Holly M; Maze, Michael J; Hertz, Julian T; Halliday, Jo EB; Allan, Kathryn J; Mmbaga, Blandina T; Saganda, Wilbrod; Lwezaula, Bingileki F; Kazwala, Rudovick R; Cleaveland, Sarah; Maro, Venance P; Crump, John AQ fever and spotted fever group rickettsioses (SFGR) are common causes of severe febrile illness in northern Tanzania. Incidence estimates are needed to characterize the disease burden. Using hybrid surveillance-coupling case-finding at two referral hospitals and healthcare utilization data-we estimated the incidences of acute Q fever and SFGR in Moshi, Kilimanjaro, Tanzania, from 2007 to 2008 and from 2012 to 2014. Cases were defined as fever and a four-fold or greater increase in antibody titers of acute and convalescent paired sera according to the indirect immunofluorescence assay of Coxiella burnetii phase II antigen for acute Q fever and Rickettsia conorii (2007-2008) or Rickettsia africae (2012-2014) antigens for SFGR. Healthcare utilization data were used to adjust for underascertainment of cases by sentinel surveillance. For 2007 to 2008, among 589 febrile participants, 16 (4.7%) of 344 and 27 (8.8%) of 307 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 80 (uncertainty range, 20-454) and 147 (uncertainty range, 52-645) per 100,000 persons, respectively. For 2012 to 2014, among 1,114 febrile participants, 52 (8.1%) and 57 (8.9%) of 641 participants with paired serology had Q fever and SFGR, respectively. Adjusted annual incidence estimates of Q fever and SFGR were 56 (uncertainty range, 24-163) and 75 (uncertainty range, 34-176) per 100,000 persons, respectively. We found substantial incidences of acute Q fever and SFGR in northern Tanzania during both study periods. To our knowledge, these are the first incidence estimates of either disease in sub-Saharan Africa. Our findings suggest that control measures for these infections warrant consideration.Item Open Access Incidence of human brucellosis in the Kilimanjaro Region of Tanzania in the periods 2007-2008 and 2012-2014.(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2018-03) Carugati, Manuela; Biggs, Holly M; Maze, Michael J; Stoddard, Robyn A; Cash-Goldwasser, Shama; Hertz, Julian T; Halliday, Jo EB; Saganda, Wilbrod; Lwezaula, Bingileki F; Kazwala, Rudovick R; Cleaveland, Sarah; Maro, Venance P; Rubach, Matthew P; Crump, John ABackground
Brucellosis causes substantial morbidity among humans and their livestock. There are few robust estimates of the incidence of brucellosis in sub-Saharan Africa. Using cases identified through sentinel hospital surveillance and health care utilization data, we estimated the incidence of brucellosis in Moshi Urban and Moshi Rural Districts, Kilimanjaro Region, Tanzania, for the periods 2007-2008 and 2012-2014.Methods
Cases were identified among febrile patients at two sentinel hospitals and were defined as having either a 4-fold increase in Brucella microscopic agglutination test titres between acute and convalescent serum or a blood culture positive for Brucella spp. Findings from a health care utilization survey were used to estimate multipliers to account for cases not seen at sentinel hospitals.Results
Of 585 patients enrolled in the period 2007-2008, 13 (2.2%) had brucellosis. Among 1095 patients enrolled in the period 2012-2014, 32 (2.9%) had brucellosis. We estimated an incidence (range based on sensitivity analysis) of brucellosis of 35 (range 32-93) cases per 100 000 persons annually in the period 2007-2008 and 33 (range 30-89) cases per 100 000 persons annually in the period 2012-2014.Conclusions
We found a moderate incidence of brucellosis in northern Tanzania, suggesting that the disease is endemic and an important human health problem in this area.Item Open Access Individualizing duration of antibiotic therapy in community-acquired pneumonia.(Pulmonary pharmacology & therapeutics, 2017-08) Aliberti, Stefano; Ramirez, Julio; Giuliani, Fabio; Wiemken, Timothy; Sotgiu, Giovanni; Tedeschi, Sara; Carugati, Manuela; Valenti, Vincenzo; Valenti, Vincenzo; Marchioni, Marco; Camera, Marco; Piro, Roberto; Del Forno, Manuela; Milani, Giuseppe; Faverio, Paola; Richeldi, Luca; Deotto, Martina; Villani, Massimiliano; Voza, Antonio; Tobaldini, Eleonora; Bernardi, Mauro; Bellone, Andrea; Bassetti, Matteo; Blasi, FrancescoInternational experts suggest tailoring antibiotic duration in community-acquired pneumonia (CAP) according to patients' characteristics. We aimed to assess the effectiveness of an individualized approach to antibiotic duration based on time in which CAP patients reach clinical stability during hospitalization. In a multicenter, non-inferiority, randomized, controlled trial hospitalized adult patients with CAP reaching clinical stability within 5 days after hospitalization were randomized to a standard vs. individualized antibiotic duration. In the Individualized group, antibiotics were discontinued 48 h after the patient reached clinical stability, with at least five days of total antibiotic treatment. Early failure within 30 days was the primary composite outcome. 135 patients were randomized to the Standard group and 125 to the Individualized group. The trial was interrupted by the safety committee because of an apparent inferiority of the Individualized group over the Standard treatment: 14 (11.2%) patients in the Individualized group experienced early failure vs. 10 (7.4%) patients in the Standard group, p = 0.200, at the intention-to-treat analysis. 30-day mortality rate was four-time higher in the Individualized group than the Standard group. Shortening antibiotic duration according to patients' characteristics still remains an open question.Item Open Access Influence of Hospitalization upon Diagnosis on the Risk of Tuberculosis Clustering.(Mediterranean journal of hematology and infectious diseases, 2013-01) Lapadula, Giuseppe; Zanini, Fabio; Codecasa, Luigi; Franzetti, Fabio; Ferrarese, Maurizio; Carugati, Manuela; Mazzola, Ester; Schiroli, Consuelo; Motta, Davide; Iemmi, Diego; Gori, AndreaSetting
Culture-positive tuberculosis (TB) diagnosed in the metropolitan area of Milan (Italy) over a 5-year period (1995-1999).Objective
To assess the impact of short-course hospitalization upon diagnosis on the overall risk of TB clustering.Design
Restriction fragment length polymorphism profiles with a similarity of 100% defined a cluster. Uni- and multivariable logistic regression models were performed to assess factors associated with clustering.Results
Among 1139 patients, 392 (34.4%) were hospitalized before or soon after diagnosis, 405 (35.6%) received domiciliary treatment since the diagnosis and 392 (30%) had no information about initial clinical management. One hundred fifteen molecular clusters involving 363 patients were identified. Using multivariable analysis, hospitalization was not significantly associated with clustering (OR 1.06, 95%CI 0.75-1.50, p=0.575). Subjects aged >65 years old (OR 0.60; 95CI%:0.37-0.95; p=0.016) and non-Italian born patients (OR 0.56; 95%CI:0.41-0.76; p<0.001) were running a lower risk of clustering. Conversely, HIV co-infected patients (OR 1.88, 95%CI:1.20-2.95, p=0.006) and those with MDR TB (OR 2.50, 95%CI:1.46-4.25, p=0.001) were significantly more likely to be involved in clusters.Conclusion
In our cohort, domiciliary treatment was not associated with TB clustering. Expanding domiciliary treatment upon diagnosis appears as an advisable measure to reduce unnecessary costs for the health care system.Item Open Access Interleukin-1 receptor antagonist anakinra in association with remdesivir in severe COVID-19: A case report.(International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2020-08) Franzetti, Marco; Pozzetti, Ugo; Carugati, Manuela; Pandolfo, Alessandro; Molteni, Chiara; Faccioli, Paolo; Castaldo, Gioacchino; Longoni, Ernesto; Ormas, Valentina; Iemoli, Enrico; Piconi, StefaniaWe report the first successful treatment with the IL-1 receptor antagonist anakinra, in association with the most promising and available antiviral therapy, of a severe case of novel coronavirus disease 2019 (COVID-19). We describe the diagnosis, clinical course, and management of the case, including the respiratory failure at presentation, the progression to a scenario characterized by profound inflammatory dysregulation similar to that observed during macrophage activation syndrome, and the clinical improvement after treatment with the IL-1 receptor antagonist anakinra. This case highlights the high tolerability and the interesting immunomodulatory profile of the IL-1 receptor antagonist anakinra in the setting of severe COVID-19 associated with remdesivir therapy. Further studies are needed to confirm the safety and efficacy of this combination strategy in the treatment of this emerging infection.Item Open Access International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia.(The Journal of infection, 2019-10) Aliberti, Stefano; Cook, Grayden S; Babu, Bettina L; Reyes, Luis F; H Rodriguez, Alejandro; Sanz, Francisco; Soni, Nilam J; Anzueto, Antonio; Faverio, Paola; Sadud, Ricardo Franco; Muhammad, Irfan; Prat, Cristina; Vendrell, Ester; Neves, Joao; Kaimakamis, Evangelos; Feneley, Andrew; Swarnakar, Rajesh; Franzetti, Fabio; Carugati, Manuela; Morosi, Manuela; Monge, Elisa; Restrepo, Marcos I; GLIMP investigatorsObjective
Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study.Design
The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility data. Multivariate logistic regressions were used to identify risk factors independently associated with DRSP-CAP.Results
3,193 subjects were included in the study. The global prevalence of DRSP-CAP was 1.3% and continental prevalence rates were 7.0% in Africa, 1.2% in Asia, and 1.0% in South America, Europe, and North America, respectively. Macrolide resistance was most frequently identified in subjects with DRSP-CAP (0.6%) followed by penicillin resistance (0.5%). Subjects in Africa were more likely to have DRSP-CAP (OR: 7.6; 95%CI: 3.34-15.35, p<0.001) when compared to centres representing other continents.Conclusions
This multinational point-prevalence study found a low global prevalence of DRSP-CAP that may impact guideline development and antimicrobial policies.Item Open Access Investigation of Melioidosis Using Blood Culture and Indirect Hemagglutination Assay Serology among Patients with Fever, Northern Tanzania.(The American journal of tropical medicine and hygiene, 2020-12) Maze, Michael J; Elrod, Mindy Glass; Biggs, Holly M; Bonnewell, John; Carugati, Manuela; Hoffmaster, Alex R; Lwezaula, Bingileki F; Madut, Deng B; Maro, Venance P; Mmbaga, Blandina T; Morrissey, Anne B; Saganda, Wilbrod; Sakasaka, Philoteus; Rubach, Matthew P; Crump, John APrediction models indicate that melioidosis may be common in parts of East Africa, but there are few empiric data. We evaluated the prevalence of melioidosis among patients presenting with fever to hospitals in Tanzania. Patients with fever were enrolled at two referral hospitals in Moshi, Tanzania, during 2007-2008, 2012-2014, and 2016-2019. Blood was collected from participants for aerobic culture. Bloodstream isolates were identified by conventional biochemical methods. Non-glucose-fermenting Gram-negative bacilli were further tested using a Burkholderia pseudomallei latex agglutination assay. Also, we performed B. pseudomallei indirect hemagglutination assay (IHA) serology on serum samples from participants enrolled from 2012 to 2014 and considered at high epidemiologic risk of melioidosis on the basis of admission within 30 days of rainfall. We defined confirmed melioidosis as isolation of B. pseudomallei from blood culture, probable melioidosis as a ≥ 4-fold rise in antibody titers between acute and convalescent sera, and seropositivity as a single antibody titer ≥ 40. We enrolled 3,716 participants and isolated non-enteric Gram-negative bacilli in five (2.5%) of 200 with bacteremia. As none of these five isolates was B. pseudomallei, there were no confirmed melioidosis cases. Of 323 participants tested by IHA, 142 (44.0%) were male, and the median (range) age was 27 (0-70) years. We identified two (0.6%) cases of probable melioidosis, and 57 (17.7%) were seropositive. The absence of confirmed melioidosis from 9 years of fever surveillance indicates melioidosis was not a major cause of illness.