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79 results on '"Giulieri, S."'

1. The Staphylococcus aureus Network Adaptive Platform Trial Protocol: New Tools for an Old Foe

Author

Tong, S.Y.C., Mora, J., Bowen, A.C., Cheng, M.P., Daneman, N., Goodman, A.L., Heriot, G.S., Lee, T.C., Lewis, R.J., Lye, D.C., Mahar, R.K., Marsh, J., McGlothlin, A., McQuilten, Z., Morpeth, S.C., Paterson, D.L., Price, D.J., Roberts, J.A., Robinson, J.O., van Hal, S.J., Walls, G., Webb, S.A., Whiteway, L., Yahav, D., Davis, J.S., Anagnostou, N., Archuleta, S., Athan, E., Best, E., Bloomfield, M., Botheras, C., Bowen, A., Britton, P., Brown, K., Campbell, A., Carter, H., Cheng, M., Chew, K.L., Chong, R.L.M., Coombs, G., Daley, P., Davies, J., Davis, J., Dishon, Y., Dotel, R., Dunlop, A., Flack, F., Flanagan, K., Foo, H., Ghanem-Zoubi, N., Giulieri, S., Goodman, A., Grant, J., Gregson, D., Guy, S., Gwee, A., Hardy, E., Henderson, A., Heriot, G., Howden, B., Johnstone, J., Kalimuddin, S., de Kretser, D., Kwa, A., Lee, T., Legg, A., Lewis, R., Lumley, T., Lye, D., MacFadden, D., Mahar, R., Malhamé, I., Marks, M., Martinello, M., Matthews, G., McArthur, C., McKew, G., McMullan, B., Milliken, E., Morpeth, S., Murthy, S., Nourse, C., O’Sullivan, M., Paterson, D., Paul, M., Petersiel, N., Petrella, L., Price, D., Roberts, J., Rogers, B., Saville, B., Scheetz, M., Scheuerman, O., Schwartz, K., Smith, S., Snelling, T., Sommerville, C., Stewardson, A., Sud, A., Tong, S., Turner, T., van Hal, S., Vasilunas, N., Voss, L., Webb, R., Webb, S., Wilson, H., Wuerz, T., Tong, S.Y.C., Mora, J., Bowen, A.C., Cheng, M.P., Daneman, N., Goodman, A.L., Heriot, G.S., Lee, T.C., Lewis, R.J., Lye, D.C., Mahar, R.K., Marsh, J., McGlothlin, A., McQuilten, Z., Morpeth, S.C., Paterson, D.L., Price, D.J., Roberts, J.A., Robinson, J.O., van Hal, S.J., Walls, G., Webb, S.A., Whiteway, L., Yahav, D., Davis, J.S., Anagnostou, N., Archuleta, S., Athan, E., Best, E., Bloomfield, M., Botheras, C., Bowen, A., Britton, P., Brown, K., Campbell, A., Carter, H., Cheng, M., Chew, K.L., Chong, R.L.M., Coombs, G., Daley, P., Davies, J., Davis, J., Dishon, Y., Dotel, R., Dunlop, A., Flack, F., Flanagan, K., Foo, H., Ghanem-Zoubi, N., Giulieri, S., Goodman, A., Grant, J., Gregson, D., Guy, S., Gwee, A., Hardy, E., Henderson, A., Heriot, G., Howden, B., Johnstone, J., Kalimuddin, S., de Kretser, D., Kwa, A., Lee, T., Legg, A., Lewis, R., Lumley, T., Lye, D., MacFadden, D., Mahar, R., Malhamé, I., Marks, M., Martinello, M., Matthews, G., McArthur, C., McKew, G., McMullan, B., Milliken, E., Morpeth, S., Murthy, S., Nourse, C., O’Sullivan, M., Paterson, D., Paul, M., Petersiel, N., Petrella, L., Price, D., Roberts, J., Rogers, B., Saville, B., Scheetz, M., Scheuerman, O., Schwartz, K., Smith, S., Snelling, T., Sommerville, C., Stewardson, A., Sud, A., Tong, S., Turner, T., van Hal, S., Vasilunas, N., Voss, L., Webb, R., Webb, S., Wilson, H., and Wuerz, T.

Abstract

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%–30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial commenced enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious disease syndromes.

Published
2022

3. CSF lactate for accurate diagnosis of community-acquired bacterial meningitis

Author

Giulieri, S., Chapuis-Taillard, C., Jaton, K., Cometta, A., Chuard, C., Hugli, O., Du Pasquier, R., Bille, J., Meylan, P., Manuel, O., Marchetti, O., Giulieri, S., Chapuis-Taillard, C., Jaton, K., Cometta, A., Chuard, C., Hugli, O., Du Pasquier, R., Bille, J., Meylan, P., Manuel, O., and Marchetti, O.

Abstract

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm3), proteins (median 4115 vs. 829mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.

Published
2021

6. Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections

Author

Guerillot, R, Kostoulias, X, Donovan, L, Li, L, Carter, GP, Hachani, A, Vandelannoote, K, Giulieri, S, Monk, IR, Kunimoto, M, Starrs, L, Burgio, G, Seemann, T, Peleg, AY, Stinear, TP, Howden, BP, Guerillot, R, Kostoulias, X, Donovan, L, Li, L, Carter, GP, Hachani, A, Vandelannoote, K, Giulieri, S, Monk, IR, Kunimoto, M, Starrs, L, Burgio, G, Seemann, T, Peleg, AY, Stinear, TP, and Howden, BP

Abstract

Staphylococcus aureus small-colony variants (SCVs) are associated with unusually chronic and persistent infections despite active antibiotic treatment. The molecular basis for this clinically important phenomenon is poorly understood, hampered by the instability of the SCV phenotype. Here we investigated the genetic basis for an unstable S. aureus SCV that arose spontaneously while studying rifampicin resistance. This SCV showed no nucleotide differences across its genome compared with a normal-colony variant (NCV) revertant, yet the SCV presented the hallmarks of S. aureus linked to persistent infection: down-regulation of virulence genes and reduced hemolysis and neutrophil chemotaxis, while exhibiting increased survival in blood and ability to invade host cells. Further genome analysis revealed chromosome structural variation uniquely associated with the SCV. These variations included an asymmetric inversion across half of the S. aureus chromosome via recombination between type I restriction modification system (T1RMS) genes, and the activation of a conserved prophage harboring the immune evasion cluster (IEC). Phenotypic reversion to the wild-type-like NCV state correlated with reversal of the chromosomal inversion (CI) and with prophage stabilization. Further analysis of 29 complete S. aureus genomes showed strong signatures of recombination between hsdMS genes, suggesting that analogous CI has repeatedly occurred during S. aureus evolution. Using qPCR and long-read amplicon deep sequencing, we detected subpopulations with T1RMS rearrangements causing CIs and prophage activation across major S. aureus lineages. Here, we have discovered a previously unrecognized and widespread mechanism of reversible genomic instability in S. aureus associated with SCV generation and persistent infections.

Published
2019

7. Genomic Exploration of Within-Host Microevolution Reveals a Distinctive Molecular Signature of Persistent Staphylococcus aureus Bacteraemia

Author

Giulieri, S, Baines, S, Guerillot, R, Semann, T, Goncalves da Silva, A, Schultz, M, Massey, R, Holmes, N, Stinear, T, Howden, B, Giulieri, S, Baines, S, Guerillot, R, Semann, T, Goncalves da Silva, A, Schultz, M, Massey, R, Holmes, N, Stinear, T, and Howden, B

Abstract

Background: Large-scale genomic studies of within-host evolution during Staphylococcus aureus bacteraemia (SAB) are needed to understanding bacterial adaptation underlying persistence and thus refining the role of genomics in management of SAB. However, available comparative genomic studies of sequential SAB isolates have tended to focus on selected cases of unusually prolonged bacteraemia, where secondary antimicrobial resistance has developed. To understand the bacterial genomic evolution during SAB more broadly, we applied whole genome sequencing to a large collection of sequential isolates obtained from patients with persistent or relapsing bacteraemia. Results: We show that, while adapation pathways are heterogenous and episode-specific, isolates from persistent bacteraemia have a distinctive molecular signature, characterised by a low mutation frequency and high proportion of non-silent mutations. By performing an extensive analysis of structural genomic variants in addition to point mutations, we found that these often overlooked genetic events are commonly acquired during SAB. We discovered that IS256 insertion may represent the most effective driver of within-host microevolution in selected lineages, with up to three new insertion events per isolate even in the absence of other mutations. Genetic mechanisms resulting in significant phenotypic changes, such as increases in vancomycin resistance, development of small colony phenotypes, and decreases in cytotoxicity, included mutations in key genes (rpoB, stp, agrA) and an IS256 insertion upstream of the walKR operon. Conclusions: This study provides for the first time a large-scale analysis of within-host evolution during invasive S. aureus infection and describes specific patterns of adaptation that will be informative for both understanding S. aureus pathoadaptation and utilising genomics for management of complicated S. aureus infections.

Published
2018

8. Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq)

Author

Guerillot, R, Li, L, Baines, S, Howden, B, Schultz, MB, Seemann, T, Monk, I, Pidot, SJ, Gao, W, Giulieri, S, da Silva, AG, D'Agata, A, Tomita, T, Peleg, AY, Stinear, TP, Howden, BP, Guerillot, R, Li, L, Baines, S, Howden, B, Schultz, MB, Seemann, T, Monk, I, Pidot, SJ, Gao, W, Giulieri, S, da Silva, AG, D'Agata, A, Tomita, T, Peleg, AY, Stinear, TP, and Howden, BP

Abstract

Mutation acquisition is a major mechanism of bacterial antibiotic resistance that remains insufficiently characterised. Here we present RM-seq, a new amplicon-based deep sequencing workflow based on a molecular barcoding technique adapted from Low Error Amplicon sequencing (LEA-seq). RM-seq allows detection and functional assessment of mutational resistance at high throughput from mixed bacterial populations. The sensitive detection of very low-frequency resistant sub-populations permits characterisation of antibiotic-linked mutational repertoires in vitro and detection of rare resistant populations during infections. Accurate quantification of resistance mutations enables phenotypic screening of mutations conferring pleiotropic phenotypes such as in vivo persistence, collateral sensitivity or cross-resistance. RM-seq will facilitate comprehensive detection, characterisation and surveillance of resistant bacterial populations ( https://github.com/rguerillot/RM-seq ).

Published
2018

9. Convergent Evolution Driven by Rifampin Exacerbates the Global Burden of Drug-Resistant &ITStaphylococcus aureus&IT

Author

Fey, PD, Guerillot, R, da Silva, AG, Monk, I, Giulieri, S, Tomita, T, Alison, E, Porter, J, Pidot, S, Gao, W, Peleg, AY, Seemann, T, Stinear, TP, Howden, BP, Fey, PD, Guerillot, R, da Silva, AG, Monk, I, Giulieri, S, Tomita, T, Alison, E, Porter, J, Pidot, S, Gao, W, Peleg, AY, Seemann, T, Stinear, TP, and Howden, BP

Abstract

Mutations in the beta-subunit of bacterial RNA polymerase (RpoB) cause resistance to rifampin (Rifr), a critical antibiotic for treatment of multidrug-resistant Staphylococcus aureus. In vitro studies have shown that RpoB mutations confer decreased susceptibility to other antibiotics, but the clinical relevance is unknown. Here, by analyzing 7,099 S. aureus genomes, we demonstrate that the most prevalent RpoB mutations promote clinically relevant phenotypic plasticity resulting in the emergence of stable S. aureus lineages, associated with increased risk of therapeutic failure through generation of small-colony variants (SCVs) and coresistance to last-line antimicrobial agents. We found eight RpoB mutations that accounted for 93% (469/505) of the total number of Rifr mutations. The most frequently selected amino acid substitutions affecting residue 481 (H481N/Y) were associated with worldwide expansions of Rifr clones spanning decades. Recreating the H481N/Y mutations confirmed no impact on S. aureus growth, but the H481N mutation promoted the emergence of a subpopulation of stable Rifr SCVs with reduced susceptibility to vancomycin and daptomycin. Recreating the other frequent RpoB mutations showed similar impacts on resistance to these last-line agents. We found that 86% of all Rifr isolates in our global sample carried the mutations promoting cross-resistance to vancomycin and 52% to both vancomycin and daptomycin. As four of the most frequent RpoB mutations confer only low-level Rifr, equal to or below some international breakpoints, we recommend decreasing these breakpoints and reconsidering the appropriate use of rifampin to reduce the fixation and spread of these clinically deleterious mutations. IMPORTANCE Increasing antibiotic resistance in the major human pathogen Staphylococcus aureus is threatening the ability to treat patients with these infections. Recent laboratory studies suggest that mutations in the gene commonly associated with rifampin resistance

Published
2018

10. Abstracts of the Eighth EDCTP Forum, 6-9 November 2016.

Author

Makanga, M, Beattie, P, Breugelmans, G, Nyirenda, T, Bockarie, M, Tanner, M, Volmink, J, Hankins, C, Walzl, G, Chegou, N, Malherbe, S, Hatherill, M, Scriba, TJ, Zak, DE, Barry, CE, Kaufmann, SHE, Noor, A, Strub-Wourgaft, N, Phillips, P, Munguambe, K, Ravinetto, R, Tinto, H, Diro, E, Mahendrahata, Y, Okebe, J, Rijal, S, Garcia, C, Sundar, S, Ndayisaba, G, Sopheak, T, Ngoduc, T, Van Loen, H, Jacobs, J, D'Alessandro, U, Boelaert, M, Buvé, A, Kamalo, P, Manda-Taylor, L, Rennie, S, Mokgatla, B, Bahati, Ijsselmuiden, C, Afolabi, M, Mcgrath, N, Kampmann, B, Imoukhuede, E, Alexander, N, Larson, H, Chandramohan, D, Bojang, K, Kasaro, MP, Muluka, B, Kaunda, K, Morse, J, Westfall, A, Kapata, N, Kruuner, A, Henostroza, G, Reid, S, Alabi, A, Foguim, F, Sankarganesh, J, Bruske, E, Mfoumbi, A, Mevyann, C, Adegnika, A, Lell, B, Kranzer, K, Kremsner, P, Grobusch, M, Sabiiti, W, Ntinginya, N, Kuchaka, D, Azam, K, Kampira, E, Mtafya, B, Bowness, R, Bhatt, N, Davies, G, Kibiki, G, Gillespie, S, Lejon, V, Ilboudo, H, Mumba, D, Camara, M, Kaba, D, Lumbala, C, Fèvre, E, Jamonneau, V, Bucheton, B, Büscher, P, Chisenga, C, Sinkala, E, Chilengi, R, Chitundu, H, Zyambo, Z, Wandeler, G, Vinikoor, M, Emilie, D, Camara, O, Mathurin, K, Guiguigbaza-Kossigan, D, Philippe, B, Regassa, F, Hassane, S, Bienvenu, SM, Fabrice, C, Ouédraogo, E, Kouakou, L, Owusu, M, Mensah, E, Enimil, A, Mutocheluh, M, Ndongo, FA, Tejiokem, MC, Texier, G, Penda, C, Ndiang, S, Ndongo, J-A, Guemkam, G, Sofeu, CL, Afumbom, K, Faye, A, Msellati, P, Warszawski, J, Vos, A, Devillé, W, Barth, R, Klipstein-Grobusch, K, Tempelman, H, Venter, F, Coutinho, R, Grobbee, D, Ssemwanga, D, Lyagoba, F, Magambo, B, Kapaata, A, Kirangwa, J, Nannyonjo, M, Nassolo, F, Nsubuga, R, Yebra, G, Brown, A, Kaleebu, P, Nylén, H, Habtewold, A, Makonnen, E, Yimer, G, Burhenne, J, Diczfalusy, U, Aklillu, E, Steele, D, Walker, R, Simuyandi, M, Beres, L, Bosomprah, S, Ansumana, R, Taitt, C, Lamin, JM, Jacobsen, KH, Mulvaney, SP, Leski, T, Bangura, U, Stenger, D, De Vries, S, Zinsou, FJ, Honkpehedji, J, Dejon, JC, Loembe, MM, Bache, B, Pakker, N, Van Leeuwen, R, Hounkpatin, AB, Yazdanbakhsh, M, Bethony, J, Hotez, P, Diemert, D, Bache, BE, Fernandes, JF, Obiang, RM, Kabwende, AL, Grobusch, MP, Krishna, S, Kremsner, PG, Todagbe, AS, Nambozi, M, Kabuya, J-B, Hachizovu, S, Mwakazanga, D, Kasongo, W, Buyze, J, Mulenga, M, Geertruyden, J-P, Gitaka, J, Chan, C, Kongere, J, Kagaya, W, Kaneko, A, Kabore, N, Barry, N, Kabre, Z, Werme, K, Fofana, A, Compaore, D, Nikiema, F, Some, F, Djimde, A, Zongo, I, Ouedraogo, B, Kone, A, Sagara, I, Björkman, A, Gil, JP, Nchinda, G, Bopda, A, Nji, N, Ambada, G, Ngu, L, Tchadji, J, Sake, C, Magagoum, S, Njambe, GD, Lisom, A, Park, CG, Tait, D, Sibusiso, H, Manda, O, Croucher, K, Van Der Westhuizen, A, Mshanga, I, Levin, J, Nanvubya, A, Kibengo, F, Jaoko, W, Pala, P, Perreau, M, Namuniina, A, Kitandwe, P, Tapia, G, Serwanga, J, Yates, N, Fast, P, Mayer, B, Montefiori, D, Tomaras, G, Robb, M, Lee, C, Wagner, R, Sanders, E, Kilembe, W, Kiwanuka, N, Gilmour, J, Kuipers, H, Vooij, D, Chinyenze, K, Priddy, F, Ding, S, Hanke, T, Pantaleo, G, Ngasala, B, Jovel, I, Malmberg, M, Mmbando, B, Premji, Z, Mårtensson, A, Mwaiswelo, R, Agbor, L, Apinjoh, T, Mwanza, S, Chileshe, J, Joshi, S, Malunga, P, Manyando, C, Laufer, M, Dara, A, Niangaly, A, Sinha, I, Brodin, D, Fofana, B, Dama, S, Dembele, D, Sidibe, B, Diallo, N, Thera, M, Wright, K, Gil, J, Doumbo, O, Baraka, V, Nabasumba, C, Francis, F, Lutumba, P, Mavoko, H, Alifrangis, M, Van Geertruyden, J-P, Sissoko, S, Sangaré, C, Toure, S, Sanogo, K, Diakite, H, Doumbia, D, Haidara, K, Julé, A, Ashurst, H, Merson, L, Olliaro, P, Marsh, V, Lang, T, Guérin, P, Awuondo, K, Njenga, D, Nyakarungu, E, Titus, P, Sutamihardja, A, Lowe, B, Ogutu, B, Billingsley, P, Soulama, I, Kaboré, M, Coulibaly, A, Ouattara, M, Sanon, S, Diarra, A, Bougouma, E, Ouedraogo, A, Sombie, B, Kargougou, D, Ouattara, D, Issa, N, Tiono, A, Sirima, S, Chaponda, M, Dabira, E, Dao, F, Dara, N, Coulibaly, M, Tolo, A, Maiga, H, Ouologuem, N, Niangaly, H, Botchway, F, Wilson, N, Dickinson-Copeland, CM, Adjei, AA, Wilson, M, Stiles, JK, Hamid, MA, Awad-Elgeid, M, Nasr, A, Netongo, P, Kamdem, S, Velavan, T, Lasry, E, Diarra, M, Bamadio, A, Traore, A, Coumare, S, Soma, B, Dicko, Y, Sangare, B, Tembely, A, Traore, D, Haidara, A, Dicko, A, Diawara, E, Beavogui, A, Camara, D, Sylla, M, Yattara, M, Sow, A, Camara, GC, Diallo, S, Mombo-Ngoma, G, Remppis, J, Sievers, M, Manego, RZ, Endamne, L, Hutchinson, D, Held, J, Supan, C, Salazar, CLO, Bonkian, LN, Nahum, A, Sié, A, Abdulla, S, Cantalloube, C, Djeriou, E, Bouyou-Akotet, M, Mordmüller, B, Siribie, M, Sirima, SB, Ouattara, SM, Coulibaly, S, Kabore, JM, Amidou, D, Tekete, M, Traore, O, Haefeli, W, Borrmann, S, Kaboré, N, Kabré, Z, Nikèma, F, Compaoré, D, Somé, F, Djimdé, A, Ouédraogo, J, Chalwe, V, Miller, J, Diakité, H, Greco, B, Spangenberg, T, Kourany-Lefoll, E, Oeuvray, C, Mulry, J, Tyagarajan, K, Magsaam, B, Barnes, K, Hodel, EM, Humphreys, G, Pace, C, Banda, CG, Denti, P, Allen, E, Lalloo, D, Mwapasa, V, Terlouw, A, Mwesigwa, J, Achan, J, Jawara, M, Ditanna, G, Worwui, A, Affara, M, Koukouikila-Koussounda, F, Kombo, M, Vouvoungui, C, Ntoumi, F, Etoka-Beka, MK, Deibert, J, Poulain, P, Kobawila, S, Gueye, NG, Seda, B, Kwambai, T, Jangu, P, Samuels, A, Kuile, FT, Kariuki, S, Barry, A, Bousema, T, Okech, B, Egwang, T, Corran, P, Riley, E, Ezennia, I, Ekwunife, O, Muleba, M, Stevenson, J, Mbata, K, Coetzee, M, Norris, D, Moneke-Anyanwoke, N, Momodou, J, Clarke, E, Scott, S, Tijani, A, Djimde, M, Vaillant, M, Samouda, H, Mensah, V, Roetynck, S, Kanteh, E, Bowyer, G, Ndaw, A, Oko, F, Bliss, C, Jagne, YJ, Cortese, R, Nicosia, A, Roberts, R, D'Alessio, F, Leroy, O, Faye, B, Cisse, B, Gerry, S, Viebig, N, Lawrie, A, Ewer, K, Hill, A, Nebie, I, Tiono, AB, Sanou, G, Konate, AT, Yaro, BJ, Sodiomon, S, Honkpehedji, Y, Agobe, JCD, Zinsou, F, Mengue, J, Richie, T, Hoffman, S, Nouatin, O, Ngoa, UA, Edoa, JR, Homoet, A, Engelhon, JE, Massinga-Louembe, M, Esen, M, Theisen, M, Sim, KL, Luty, AJ, Moutairou, K, Dinko, B, King, E, Targett, G, Sutherland, C, Likhovole, C, Ouma, C, Vulule, J, Musau, S, Khayumbi, J, Okumu, A, Murithi, W, Otu, J, Gehre, F, Zingue, D, Kudzawu, S, Forson, A, Mane, M, Rabna, P, Diarra, B, Kayede, S, Adebiyi, E, Kehinde, A, Onyejepu, N, Onubogu, C, Idigbe, E, Ba, A, Diallo, A, Mboup, S, Disse, K, Kadanga, G, Dagnra, Y, Baldeh, I, Corrah, T, De Jong, B, Antonio, M, Musanabaganwa, C, Musabyimana, JP, Karita, E, Diop, B, Nambajimana, A, Dushimiyimana, V, Karame, P, Russell, J, Ndoli, J, Hategekimana, T, Sendegeya, A, Condo, J, Binagwaho, A, Okonko, I, Okerentugba, P, Opaleye, O, Awujo, E, Frank-Peterside, N, Moyo, S, Kotokwe, K, Mohammed, T, Boleo, C, Mupfumi, L, Chishala, S, Gaseitsiwe, S, Tsalaile, L, Bussmann, H, Makhema, J, Baum, M, Marlink, R, Engelbretch, S, Essex, M, Novitsky, V, Saka, E, Kalipalire, Z, Bhairavabhotla, R, Midiani, D, Sherman, J, Mgode, G, Cox, C, Bwana, D, Mtui, L, Magesa, D, Kahwa, A, Mfinanga, G, Mulder, C, Borain, N, Petersen, L, Du Plessis, J, Theron, G, Holm-Hansen, C, Tekwu, EM, Sidze, LK, Assam, JPA, Eyangoh, S, Niemann, S, Beng, VP, Frank, M, Atiadeve, S, Hilmann, D, Awoniyi, D, Baumann, R, Kriel, B, Jacobs, R, Kidd, M, Loxton, A, Kaempfer, S, Singh, M, Mwanza, W, Milimo, D, Moyo, M, Kasese, N, Cheeba-Lengwe, M, Munkondya, S, Ayles, H, De Haas, P, Muyoyeta, M, Namuganga, AR, Kizza, HM, Mendy, A, Tientcheu, L, Ayorinde, A, Coker, E, Egere, U, Coussens, A, Naude, C, Chaplin, G, Noursadeghi, M, Martineau, A, Jablonski, N, Wilkinson, R, Ouedraogo, HG, Matteelli, A, Regazzi, M, Tarnagda, G, Villani, P, Sulis, G, Diagbouga, S, Roggi, A, Giorgetti, F, Kouanda, S, Bidias, A, Ndjonka, D, Olemba, C, Souleymanou, A, Mukonzo, J, Kuteesa, R, Ogwal-Okeng, J, Gustafsson, LL, Owen, J, Bassi, P, Gashau, W, Olaf, K, Dodoo, A, Okonkwo, P, Kanki, P, Maruapula, D, Seraise, B, Einkauf, K, Reilly, A, Rowley, C, Musonda, R, Framhein, A, Mpagama, S, 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Chaplin, G, Noursadeghi, M, Martineau, A, Jablonski, N, Wilkinson, R, Ouedraogo, HG, Matteelli, A, Regazzi, M, Tarnagda, G, Villani, P, Sulis, G, Diagbouga, S, Roggi, A, Giorgetti, F, Kouanda, S, Bidias, A, Ndjonka, D, Olemba, C, Souleymanou, A, Mukonzo, J, Kuteesa, R, Ogwal-Okeng, J, Gustafsson, LL, Owen, J, Bassi, P, Gashau, W, Olaf, K, Dodoo, A, Okonkwo, P, Kanki, P, Maruapula, D, Seraise, B, Einkauf, K, Reilly, A, Rowley, C, Musonda, R, Framhein, A, Mpagama, S, Semvua, H, Maboko, L, Hoelscher, M, Heinrich, N, Mulenga, L, Kaayunga, C, Davies, M-A, Egger, M, Musukuma, K, Dambe, R, Usadi, B, Ngari, M, Thitiri, J, Mwalekwa, L, Fegan, G, Berkley, J, Nsagha, D, Munamunungu, V, Bolton, C, Siyunda, A, Shilimi, J, Bucciardini, R, Fragola, V, Abegaz, T, Lucattini, S, Halifom, A, Tadesse, E, Berhe, M, Pugliese, K, De Castro, P, Terlizzi, R, Fucili, L, Di Gregorio, M, Mirra, M, Zegeye, T, Binelli, A, Vella, S, Abraham, L, Godefay, H, Rakotoarivelo, R, Raberahona, M, Randriamampionona, N, Andriamihaja, R, Rasamoelina, T, Cornet, M, De Dieu Randria, MJ, Benet, T, Vanhems, P, Andrianarivelo, MR, Chirwa, U, Michelo, C, Hamoonga, R, Wandiga, S, Oduor, P, Agaya, J, Sharma, A, Cavanaugh, S, Cain, K, Mukisa, J, Mupere, E, Worodria, W, Ngom, JT, Koro, F, Godwe, C, Adande, C, Ateugieu, R, Onana, T, Ngono, A, Kamdem, Y, Ngo-Niobe, S, Etoa, F-X, Kanengoni, M, Ruzario, S, Ndebele, P, Shana, M, Tarumbiswa, F, Musesengwa, R, Gutsire, R, Fisher, K, Thyagarajan, B, Akanbi, O, Binuyo, M, Ssengooba, W, Respeito, D, Mambuque, E, Blanco, S, Mandomando, I, Cobelens, F, Garcia-Basteiro, A, Tamene, A, Topp, S, Mwamba, C, Padian, N, Sikazwe, I, Geng, E, Holmes, C, Sikombe, K, Hantuba, Czaicki, N, Simbeza, S, Somwe, P, Umulisa, M, Ilo, J, Kestelyn, E, Uwineza, M, Agaba, S, Delvaux, T, Wijgert, J, Gethi, D, Odeny, L, Tamandjou, C, Kaindjee-Tjituka, F, Brandt, L, Cotton, M, Nel, E, Preiser, W, Andersson, M, Adepoju, A, Magana, M, Etsetowaghan, A, Chilikwazi, M, Sutcliffe, C, Thuma, P, Sinywimaanzi, K, Matakala, H, Munachoonga, P, Moss, W, Masenza, IS, Geisenberger, O, Agrea, P, Rwegoshora, F, Mahiga, H, Olomi, W, Kroidl, A, Kayode, G, Amoakoh-Coleman, M, Ansah, E, Uthman, O, Fokam, J, Santoro, M-M, Musolo, C, Chimbiri, I, Chikwenga, G, Deula, R, Massari, R, Lungu, A, Perno, C-F, Ndzengue, G, Loveline, N, Lissom, A, Flaurent, T, Sosso, S, Essomba, C, Kpeli, G, Otchere, I, Lamelas, A, Buultjens, A, Bulach, D, Baines, S, Seemann, T, Giulieri, S, Nakobu, Z, Aboagye, S, Owusu-Mireku, E, Danso, E, Hauser, J, Hinic, V, Pluschke, G, Stinear, T, Yeboah-Manu, D, Elshayeb, A, Siddig, ME, Ahmed, AA, Hussien, AE, Kabwe, M, Tembo, J, Chilukutu, L, Chilufya, M, Ngulube, F, Lukwesa, C, Enne, V, Wexner, H, Mwananyanda, L, Hamer, D, Sinyangwe, S, Ahmed, Y, Klein, N, Maeurer, M, Zumla, A, Bates, M, Beyala, L, Etienne, G, Anthony, N, Benjamin, A, Ateudjieu, J, Chibwe, B, Ojok, D, Tarr, CA, Perez, GM, Omeonga, S, Kibungu, F, Meyer, A, Lansana, P, Mayor, A, Onyango, P, Van Loggerenberg, F, Furtado, T, Boggs, L, Segrt, A, Dochez, C, Burnett, R, Mphahlele, MJ, Miiro, G, Mbidde, E, Peshu, N, Kivaya, E, Ngowi, B, Kavishe, R, Maowia, M, Sandstrom, E, Ayuo, E, Mmbaga, B, Leisegang, C, Thorpe, M, Batchilly, E, N'Guessan, J-P, Kanteh, D, Søfteland, S, Sebitloane, M, Vwalika, B, Taylor, M, Galappaththi-Arachchige, H, Holmen, S, Gundersen, SG, Ndhlovu, P, Kjetland, EF, Kombe, F, Toohey, J, Pienaar, E, Kredo, T, Cham, PM, Abubakar, I, Dondeh, BL, Vischer, N, Pfeiffer, C, Burri, C, Musukwa, K, Zürcher, S, Mwandu, T, Bauer, S, Adriko, M, Mwaura, P, Omolloh, K, Jones, C, Malecela, M, Hamidu, BA, Jenner, TE, Asiedu, LJ, Osei-Atweneboana, M, Afeke, I, Addo, P, Newman, M, Durnez, L, Eddyani, M, Ammisah, N, Abas, M, Quartey, M, Ablordey, A, Akinwale, O, Adeneye, A, Ezeugwu, S, Olukosi, Y, Adewale, B, Sulyman, M, Mafe, M, Okwuzu, J, Gyang, P, Nwafor, T, Henry, U, Musa, B, Ujah, I, Agobé, JCD, Grau-Pujol, B, Sacoor, C, Nhabomba, A, Casellas, A, Quintó, L, Subirà, C, Giné, R, Valentín, A, Muñoz, J, Nikiema, M, Ky-Ba, A, Comapore, KAM, Sangare, L, Oluremi, A, Michel, M, Camara, Y, Sanneh, B, Cuamba, I, Gutiérrez, J, Lázaro, C, Mejia, R, Adedeji, A, Folorunsho, S, Demehin, P, Akinsanya, B, Cowley, G, Da Silva, ET, Nabicassa, M, De Barros, PDP, Blif, MM, Bailey, R, Last, A, Mahendradhata, Y, Gotuzzo, E, De Nys, K, Casteels, M, Nona, SK, Lumeka, K, Todagbe, A, Djima, MM, Ukpong, M, Sagay, A, Khamofu, H, Torpey, K, Afiadigwe, E, Anenih, J, Ezechi, O, Nweneka, C, Idoko, J, Muhumuza, S, Katahoire, A, Nuwaha, F, Olsen, A, Okeyo, S, Omollo, R, Kimutai, R, Ochieng, M, Egondi, T, Moonga, C, Chileshe, C, Magwende, G, Anumudu, C, Onile, O, Oladele, V, Adebayo, A, Awobode, H, Oyeyemi, O, Odaibo, A, Kabuye, E, Lutalo, T, Njua-Yafi, C, Nkuo-Akenji, T, Anchang-Kimbi, J, Mugri, R, Chi, H, Tata, R, Njumkeng, C, Dodoo, D, Achidi, E, Fernandes, J, Bache, EB, Matakala, K, Searle, K, Greenman, M, and Rainwater-Lovett, K

Published
2017

11. Drug resistance and genetic profile of bacterial species associated with Buruli ulcer wound infections in two districts of Ghana

Author

Kpeli, G, Otchere, I, Lamelas, A, Buultjens, A, Bulach, D, Baines, S, Seemann, T, Giulieri, S, Nakobu, Z, Aboagye, S, Owusu-Mireku, E, Danso, E, Hauser, J, Hinic, V, Pluschke, G, Stinear, T, Yeboah-Manu, D, Kpeli, G, Otchere, I, Lamelas, A, Buultjens, A, Bulach, D, Baines, S, Seemann, T, Giulieri, S, Nakobu, Z, Aboagye, S, Owusu-Mireku, E, Danso, E, Hauser, J, Hinic, V, Pluschke, G, Stinear, T, and Yeboah-Manu, D

Abstract

Background: We identified secondary infection of Buruli ulcer (BU) wounds as a cause of healing delay. In order to contribute to the improvement of wound management and reduction of healing delay, we initiated a study to gain understanding of the possible routes of infection and also characterised the resistant profiles of Gram negative bacteria isolated from the wounds of patients attending two health facilities in Ghana. Methods: Staphylococcus aureus isolates were characterised by the spa gene, mecA and the Pantone Valentine Leukocidin (PVL) toxin followed by spa sequencing and whole genome sequencing of a subset of isolates. Phenotypic antibiotic susceptibility testing of Gram negative clinical isolates was performed and multidrug-resistant Pseudomonas aeruginosa identified. The Enterobacteriaceae were further investigated for ESBL and carbapenem production, and some resistance conferring genes were analysed by PCR. Results: Twenty-four isolates were identified as methicillin-resistant S. aureus (MRSA), and lukFS genes encoding PVL were identified in 67 isolates. Typing and sequencing of the spa gene from 91 isolates identified 29 different spa types with t355 (ST152), t186 (ST88), and t346 dominating. While many distinct strains were isolated from both health centres, genotype clustering was identified within centres pointing to possible health care-associated transmission. Phylogenomic analysis confirmed these clusters. Among the GNB, phenotype screening showed widespread resistance to ampicillin, chloramphenicol, ticarcillin-clavulanic acid, cefuroxime and sulphamethoxazole-trimethoprim. ESBL production was confirmed in 15 isolates phenotypically while 61.5% of screen-positive isolates harboured at least one ESBL-conferring gene. Carbapenem encoding genes were detected in 41% of the isolates. Conclusions: Our findings indicate that the health-care environment likely contributes to superinfection of BU wounds and calls for training in wound management and infe

Published
2017

13. Possible healthcare-associated transmission as a cause of secondary infection and population structure of Staphylococcus aureus isolates from two wound treatment centres in Ghana

Author

Kpeli, G., primary, Darko Otchere, I., additional, Lamelas, A., additional, Buultjens, A., additional, Bulach, D., additional, Baines, S.L., additional, Seemann, T., additional, Giulieri, S., additional, Nakobu, Z., additional, Aboagye, S.Y., additional, Owusu-Mireku, E., additional, Pluschke, G., additional, Stinear, T.P., additional, and Yeboah-Manu, D., additional

Published
2016
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14. Fluorescein and indocyanine-green angiography in ocular syphilis: An exploratory study

Author

Balaskas, K. Sergentanis, T.N. Giulieri, S. Guex-Crosier, Y.

Abstract

Background Fluorescein (FA) and indocyanine-green angiography (ICGA) may offer valuable information concerning disease severity and prognosis in ocular syphilis. The aim of the present study is to describe angiographic patterns encountered in the context of ocular syphilis, and to explore the associations between specific angiographic manifestations and severity of disease presentation, as well as disease evolution after treatment. Methods We performed a retrospective institutional study with the inclusion of 23 patients with ocular syphilis presenting to the uveitis clinic of the Jules-Gonin Eye Hospital in a 10-year period. FA and ICGAwere performed following a standard protocol for posterior uveitis. Patterns of fluorescence were noted, and statistical associations between each angiographic pattern and any demographic, clinical, or laboratory parameter at baseline and after treatment were sought. Results The presence of any dark dots in ICGA was significantly associated with anterior uveitis (p=0.031). The presence of hot spots in ICGA was significantly associated with longer duration of symptoms prior to initial visit (p= 0.032) and with male gender (p=0.012). Weak nonsignificant trends were found associating vascular staining in FAwith anterior uveitis (p=0.066), vitritis (p=0.069), and younger age (p=0.061), as well as disc hyperfluorescence in FA with seropositivity for HIV (p=0.089) and macular edema in FA with longer disease duration (p=0.061). The presence of any dark dots in ICGA exhibited a weak trend of association with anterior uveitis and/or vitritis (p=0.079). Conclusions Out of the several associations identified implicating specific angiographic features, we underline the possible role of the presence of dark dots in ICGA for identifying active inflammation, and the role of hot spots in ICGA as markers of long-standing disease. Vascular staining in FA appears to be more common in patients with severe ocular inflammation with presence of anterior uveitis and/or vitritis. © 2011 Springer-Verlag.

Published
2012

15. Analysis of significant factors influencing visual acuity in ocular syphilis

Author

Balaskas, K. Sergentanis, T.N. Giulieri, S. Guex-Crosier, Y.

Subjects
genetic structures, eye diseases
Abstract

Background: The aim of this study is to determine whether statistical associations can be demonstrated in ocular syphilis between baseline clinical and laboratory parameters with visual acuity at presentation and with any change in visual acuity after treatment. Methods: Charts of 26 patients (42 eyes) with ocular syphilis presenting to the Uveitis clinic of the Jules-Gonin Eye Hospital were reviewed. A baseline cross-sectional analysis was performed in order to identify any association between visual acuity at presentation and demographic, clinical or laboratory parameters. After treatment, any analogy between these parameters and a change in visual acuity was subsequently assessed in a series of univariate comparisons. Results: The following factors were associated with worse initial visual acuity: severity of visual field impairment at presentation (p=0.012), macular oedema (p=0.004) and optic neuropathy (p=0.031). There was a borderline association with the presence of vasculitis on fluroangiography (p=0.072). Improvement in best corrected visual acuity after treatment was significantly associated with the presence of vasculitis on fluroangiography (p=0.005), neurosyphilis, according to lumbar puncture findings (p=0.037) and marginally with anterior uveitis (p=0.070). Inflammation relapse was associated with the coexistence of pain as presenting sign (p

Published
2011

19. Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients

Author

Metzner, K J, Giulieri, S G, Knoepfel, S A, Rauch, P, Burgisser, P, Yerly, S, Günthard, H F, Cavassini, M, Metzner, K J, Giulieri, S G, Knoepfel, S A, Rauch, P, Burgisser, P, Yerly, S, Günthard, H F, and Cavassini, M

Abstract

BACKGROUND: Early virological failure of antiretroviral therapy associated with the selection of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients is very critical, because virological failure significantly increases the risk of subsequent failures. Therefore, we evaluated the possible role of minority quasispecies of drug-resistant human immunodeficiency virus type 1, which are undetectable at baseline by population sequencing, with regard to early virological failure. METHODS: We studied 4 patients who experienced early virological failure of a first-line regimen of lamivudine, tenofovir, and either efavirenz or nevirapine and 18 control patients undergoing similar treatment without virological failure. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. RESULTS: Before treatment, none of the viruses showed any evidence of drug resistance in the standard genotype analysis. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. In contrast, all 4 patients whose treatment was failing had harbored drug-resistant viruses at low frequencies before treatment, with a frequency range of 0.07%-2.0%. A range of 1-4 mutations was detected in viruses from each patient. Most of the minority quasispecies were rapidly selected and represented the major virus population within weeks after the patients started antiretroviral therapy. All 4 patients showed good adherence to treatment. Nonnucleoside reverse-transcriptase inhibitor plasma concentrations were in normal ranges for all 4 patients at 2 separate assessment times. CONCLUSIONS: Minority quasispecies of drug-resistant viruses, detected at baseline, can rapidly outgrow and become the major virus population and subsequently lead to early therapy failure

Published
2009

31. [Skin infections due to rapid-growing mycobacteria]

Author

Gervais P, Oriol Manuel, Jaton K, and Giulieri S

Subjects
Adult, Aged, 80 and over, Male, Mycobacterium Infections, Debridement, Humans, Female, Skin Diseases, Bacterial, Middle Aged, Anti-Bacterial Agents
Abstract

Rapid-growing mycobacteria (e.g. M. abscessus and M. chelonae) are emerging pathogens with various clinical manifestations. Among immunocompetent individuals, rapid-growing mycobacteria may be responsible of pulmonary, cutaneous, osteoarticular and postoperative infections, as well as lymphadenitis and catheter-associated infections. Among immunocompromised patients, disseminated infections are also observed. Diagnosis relies on specific microbiological investigations to confirm etiology and guide antibiotic treatment. The treatment requires a multi-disciplinary approach that includes specific long-term antibiotic treatment, surgical debridement and reduction of immunosuppression whenever possible.

33. CSF lactate for accurate diagnosis of community-acquired bacterial meningitis

Author

Giulieri, S., Chapuis-Taillard, C., Jaton, K., Cometta, A., Chuard, C., Hugli, O., Du Pasquier, R., Bille, J., Meylan, P., Manuel, O., Marchetti, O., Giulieri, S., Chapuis-Taillard, C., Jaton, K., Cometta, A., Chuard, C., Hugli, O., Du Pasquier, R., Bille, J., Meylan, P., Manuel, O., and Marchetti, O.

Abstract

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm3), proteins (median 4115 vs. 829mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.

34. Genomic investigation and clinical correlates of the in vitro β-lactam: NaHCO 3 responsiveness phenotype among methicillin-resistant Staphylococcus aureus isolates from a randomized clinical trial.

Author

Petersiel N, Giulieri S, Daniel DS, Fan S-H, Ersoy SC, Davis JS, Bayer AS, Howden BP, and Tong SYC

Subjects
Humans, Bacteremia drug therapy, Bacteremia microbiology, Phenotype, beta-Lactams pharmacology, beta-Lactams therapeutic use, Male, Sodium Bicarbonate pharmacology, Female, Middle Aged, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus genetics, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Cefazolin pharmacology, Cefazolin therapeutic use, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Oxacillin pharmacology
Abstract

NaHCO 3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO 3 . NaHCO 3 responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO 3 -responsive strains with β-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus ) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO 3 . Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO 3 were considered "NaHCO 3 -responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO 3 -responsive and non-responsive strains, and that were assigned to combination treatment with a β-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO 3 -responsive to cefazolin and oxacillin, respectively. The NaHCO 3 -responsive phenotype was significantly associated with sequence type 93, SCC mec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a β-lactam, there was no association between the NaHCO 3 -responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro β-lactam-NaHCO 3 -responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a β-lactam., Competing Interests: The authors declare no conflict of interest.

Published
2024
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35. Stapled Porcine Pericardium Displays Lower Infectivity In Vitro Than Native and Sutured Porcine Pericardium.

Author

Del Tatto B, Le Roy D, Lambelet M, Corpataux JM, Chakfé N, Giulieri S, Allagnat F, Roger T, and Saucy F

Subjects
Animals, Escherichia coli, Humans, Pericardium, Silver, Staphylococcus aureus, Staphylococcus epidermidis, Swine, Blood Vessel Prosthesis, Polyethylene Terephthalates
Abstract

Background: Biological xenografts using tubulized porcine pericardium are an alternative to replace infected prosthetic graft. We recently reported an innovative technique using a stapled porcine pericardial bioconduit for immediate vascular reconstruction in emergency. The objective of this study is to compare the growth and adherence to grafts of bacteria and yeast incubated with stapled porcine pericardium, sutured or naked pericardium., Material and Methods: One square centimeter of porcine pericardial patches, with or without staples or sutures, was incubated with 10 5 colony forming units of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans for 1, 6, and 24 h. The medium was collected to quantify planktonic microorganisms, while grafts were sonicated to quantify adherent microorganisms. Dacron and Dacron Silver were analyzed in parallel as synthetic reference prostheses., Results: Stapled porcine pericardium reduced the growth and the adherence of E coli (2- to 30-fold; P < 0.0005), S aureus (11- to 1000-fold; P < 0.0006), S epidermidis (>500-fold; P < 0.0001), and C albicans (12- to 50-fold; P < 0.0001) when compared to medium alone (growth) and pericardium or Dacron (adherence). Native and sutured porcine pericardium interfered with the growth and the adherence of E coli and C albicans, and Dacron with that of S epidermidis. As expected, Dacron Silver was robustly bactericidal., Conclusions: Stapled porcine pericardium exhibited a lower susceptibility to infection by bacteria and yeasts in vitro when compared to the native and sutured porcine pericardium. Stapled porcine pericardium might be a good option for rapid vascular grafting without increasing infectivity., (Copyright © 2021. Published by Elsevier Inc.)

Published
2022
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36. Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections.

Author

Guérillot R, Kostoulias X, Donovan L, Li L, Carter GP, Hachani A, Vandelannoote K, Giulieri S, Monk IR, Kunimoto M, Starrs L, Burgio G, Seemann T, Peleg AY, Stinear TP, and Howden BP

Subjects
Chromosome Inversion, Gene Order, Genome, Bacterial, Hemolysis, Humans, Staphylococcus Phages physiology, Staphylococcus aureus virology, Chromosomal Instability, Chromosomes, Bacterial, Phenotype, Staphylococcal Infections microbiology, Staphylococcus aureus genetics, Translocation, Genetic
Abstract

Staphylococcus aureus small-colony variants (SCVs) are associated with unusually chronic and persistent infections despite active antibiotic treatment. The molecular basis for this clinically important phenomenon is poorly understood, hampered by the instability of the SCV phenotype. Here we investigated the genetic basis for an unstable S. aureus SCV that arose spontaneously while studying rifampicin resistance. This SCV showed no nucleotide differences across its genome compared with a normal-colony variant (NCV) revertant, yet the SCV presented the hallmarks of S. aureus linked to persistent infection: down-regulation of virulence genes and reduced hemolysis and neutrophil chemotaxis, while exhibiting increased survival in blood and ability to invade host cells. Further genome analysis revealed chromosome structural variation uniquely associated with the SCV. These variations included an asymmetric inversion across half of the S. aureus chromosome via recombination between type I restriction modification system (T1RMS) genes, and the activation of a conserved prophage harboring the immune evasion cluster (IEC). Phenotypic reversion to the wild-type-like NCV state correlated with reversal of the chromosomal inversion (CI) and with prophage stabilization. Further analysis of 29 complete S. aureus genomes showed strong signatures of recombination between hsdMS genes, suggesting that analogous CI has repeatedly occurred during S. aureus evolution. Using qPCR and long-read amplicon deep sequencing, we detected subpopulations with T1RMS rearrangements causing CIs and prophage activation across major S. aureus lineages. Here, we have discovered a previously unrecognized and widespread mechanism of reversible genomic instability in S. aureus associated with SCV generation and persistent infections., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Published
2019
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37. Successful treatment with daptomycin and ceftaroline of MDR Staphylococcus aureus native valve endocarditis: a case report.

Author

Duss FR, Garcia de la Mària C, Croxatto A, Giulieri S, Lamoth F, Manuel O, and Miró JM

Subjects
Aged, 80 and over, Community-Acquired Infections diagnosis, Community-Acquired Infections drug therapy, Community-Acquired Infections microbiology, Drug Synergism, Endocarditis diagnosis, Endocarditis microbiology, Fosfomycin pharmacology, Humans, Male, Microbial Sensitivity Tests, Staphylococcal Infections diagnosis, Staphylococcal Infections microbiology, Ceftaroline, Anti-Bacterial Agents therapeutic use, Cephalosporins therapeutic use, Daptomycin therapeutic use, Endocarditis drug therapy, Methicillin-Resistant Staphylococcus aureus drug effects, Staphylococcal Infections drug therapy
Abstract

Objectives: The best therapeutic approach for treating MRSA endocarditis remains unknown, particularly in cases of high vancomycin MICs. We report here a case of daptomycin-non-susceptible, ceftaroline-resistant and fosfomycin-resistant MRSA native left valve endocarditis that was successfully treated with valve repair and a combination of high-dose daptomycin and ceftaroline., Methods: Antimicrobial testing of the clinical strain was performed using Etest and microdilution broth methods. Time-kill and chequerboard methodologies were used to test the activity of antibiotic combinations., Results: By Etest, the MIC of vancomycin was 2 mg/L, the MIC of daptomycin was 2 mg/L, the MIC of fosfomycin was 1024 mg/L and the MIC of ceftaroline was 1.5 mg/L. At the standard inoculum (105 cfu/mL), the three combinations of daptomycin plus ceftaroline, cloxacillin or fosfomycin were synergistic and bactericidal. However, when these combinations were tested using a higher inoculum (108 cfu/mL), all combinations were synergistic, but only daptomycin plus ceftaroline had bactericidal activity., Conclusions: These results confirmed a synergistic effect between daptomycin plus ceftaroline and increased bactericidal activity against MRSA, suggesting that this combination may be effective for the treatment of invasive MRSA infection. Our experience highlights the potential clinical use of synergy testing to guide difficult treatment decisions in patients with MDR MRSA infection., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2019
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38. Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq).

Author

Guérillot R, Li L, Baines S, Howden B, Schultz MB, Seemann T, Monk I, Pidot SJ, Gao W, Giulieri S, Gonçalves da Silva A, D'Agata A, Tomita T, Peleg AY, Stinear TP, and Howden BP

Subjects
Anti-Bacterial Agents pharmacology, Daptomycin pharmacology, Genetic Pleiotropy, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis genetics, Rifampin pharmacology, Staphylococcus aureus drug effects, Staphylococcus aureus genetics, Drug Resistance, Bacterial genetics, Mutation
Abstract

Mutation acquisition is a major mechanism of bacterial antibiotic resistance that remains insufficiently characterised. Here we present RM-seq, a new amplicon-based deep sequencing workflow based on a molecular barcoding technique adapted from Low Error Amplicon sequencing (LEA-seq). RM-seq allows detection and functional assessment of mutational resistance at high throughput from mixed bacterial populations. The sensitive detection of very low-frequency resistant sub-populations permits characterisation of antibiotic-linked mutational repertoires in vitro and detection of rare resistant populations during infections. Accurate quantification of resistance mutations enables phenotypic screening of mutations conferring pleiotropic phenotypes such as in vivo persistence, collateral sensitivity or cross-resistance. RM-seq will facilitate comprehensive detection, characterisation and surveillance of resistant bacterial populations ( https://github.com/rguerillot/RM-seq ).

Published
2018
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39. Convergent Evolution Driven by Rifampin Exacerbates the Global Burden of Drug-Resistant Staphylococcus aureus .

Author

Guérillot R, Gonçalves da Silva A, Monk I, Giulieri S, Tomita T, Alison E, Porter J, Pidot S, Gao W, Peleg AY, Seemann T, Stinear TP, and Howden BP

Abstract

Mutations in the beta-subunit of bacterial RNA polymerase (RpoB) cause resistance to rifampin (Rif r ), a critical antibiotic for treatment of multidrug-resistant Staphylococcus aureus . In vitro studies have shown that RpoB mutations confer decreased susceptibility to other antibiotics, but the clinical relevance is unknown. Here, by analyzing 7,099 S. aureus genomes, we demonstrate that the most prevalent RpoB mutations promote clinically relevant phenotypic plasticity resulting in the emergence of stable S. aureus lineages, associated with increased risk of therapeutic failure through generation of small-colony variants (SCVs) and coresistance to last-line antimicrobial agents. We found eight RpoB mutations that accounted for 93% (469/505) of the total number of Rif r mutations. The most frequently selected amino acid substitutions affecting residue 481 (H481N/Y) were associated with worldwide expansions of Rif r clones spanning decades. Recreating the H481N/Y mutations confirmed no impact on S. aureus growth, but the H481N mutation promoted the emergence of a subpopulation of stable Rif r SCVs with reduced susceptibility to vancomycin and daptomycin. Recreating the other frequent RpoB mutations showed similar impacts on resistance to these last-line agents. We found that 86% of all Rif r isolates in our global sample carried the mutations promoting cross-resistance to vancomycin and 52% to both vancomycin and daptomycin. As four of the most frequent RpoB mutations confer only low-level Rif r , equal to or below some international breakpoints, we recommend decreasing these breakpoints and reconsidering the appropriate use of rifampin to reduce the fixation and spread of these clinically deleterious mutations. IMPORTANCE Increasing antibiotic resistance in the major human pathogen Staphylococcus aureus is threatening the ability to treat patients with these infections. Recent laboratory studies suggest that mutations in the gene commonly associated with rifampin resistance may also impact susceptibility to other last-line antibiotics in S. aureus ; however, the overall frequency and clinical impact of these mutations are unknown. By mining a global collection of clinical S. aureus genomes and by mutagenesis experiments, this work reveals that common rifampin-induced rpoB mutations promote phenotypic plasticity that has led to the global emergence of stable, multidrug-resistant S. aureus lineages that are associated with increased risk of therapeutic failure through coresistance to other last-line antimicrobials. We recommend decreasing susceptibility breakpoints for rifampin to allow phenotypic detection of critical rpoB mutations conferring low resistance to rifampin and reconsidering the appropriate use of rifampin to reduce the fixation and spread of these deleterious mutations globally.

Published
2018
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40. Genomic analysis of ST88 community-acquired methicillin resistant Staphylococcus aureus in Ghana.

Author

Kpeli G, Buultjens AH, Giulieri S, Owusu-Mireku E, Aboagye SY, Baines SL, Seemann T, Bulach D, Gonçalves da Silva A, Monk IR, Howden BP, Pluschke G, Yeboah-Manu D, and Stinear T

Abstract

Background: The emergence and evolution of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) strains in Africa is poorly understood. However, one particular MRSA lineage called ST88, appears to be rapidly establishing itself as an "African" CA-MRSA clone. In this study, we employed whole genome sequencing to provide more information on the genetic background of ST88 CA-MRSA isolates from Ghana and to describe in detail ST88 CA-MRSA isolates in comparison with other MRSA lineages worldwide., Methods: We first established a complete ST88 reference genome (AUS0325) using PacBio SMRT sequencing. We then used comparative genomics to assess relatedness among 17 ST88 CA-MRSA isolates recovered from patients attending Buruli ulcer treatment centres in Ghana, three non-African ST88s and 15 other MRSA lineages., Results: We show that Ghanaian ST88 forms a discrete MRSA lineage (harbouring SCC mec- IV [2B]). Gene content analysis identified five distinct genomic regions enriched among ST88 isolates compared with the other S. aureus lineages. The Ghanaian ST88 isolates had only 658 core genome SNPs and there was no correlation between phylogeny and geography, suggesting the recent spread of this clone. The lineage was also resistant to multiple classes of antibiotics including β -lactams, tetracycline and chloramphenicol., Discussion: This study reveals that S. aureus ST88-IV is a recently emerging and rapidly spreading CA-MRSA clone in Ghana. The study highlights the capacity of small snapshot genomic studies to provide actionable public health information in resource limited settings. To our knowledge this is the first genomic assessment of the ST88 CA-MRSA clone., Competing Interests: Timothy Stinear is an Academic Editor for PeerJ.

Published
2017
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41. Bacillus cereus bacteraemia: comparison between haematologic and nonhaematologic patients.

Author

Tusgul S, Prod'hom G, Senn L, Meuli R, Bochud PY, and Giulieri SG

Abstract

Bacillus cereus bacteraemia can be severe, especially among patients with haematologic malignancy. We retrospectively reviewed first episodes of true B. cereus bacteraemia (more than one positive bottle plus signs of infection) at our institution between 1997 and 2013 with the aim to compare haematologic versus nonhaematologic patients and analyse episodes with complicated outcome. Among 56 episodes of positive-blood cultures for B. cereus, 21 were considered significant. Median age was 54 years (range 23-82 years). Ten patients (48%) had a haematologic malignancy; all were neutropenic at the time of B. cereus bacteraemia. Nonhaematologic patients were either intravenous drug users ( n  = 3, 14%), polytraumatized ( n  = 3, 14%) or had multiple chronic comorbidities ( n  = 5, 24%). Most episodes were hospital acquired (15, 71%). Sources of bacteraemia were intravascular catheter ( n  = 11, 52%), digestive tract ( n  = 6, 29%), drug injection ( n  = 3, 14%) and wound ( n  = 1, 5%). Adequate antibiotic therapy was provided to 18 patients (86%) during a median of 17 days (range 2-253 days). The intravascular catheter was removed in eight cases (42%). Three haematologic patients had a complicated course with neurologic complications (meningoencephalitis and cerebral abscesses). Complications appeared to be associated with catheter infection (100% of complicated cases vs. 29% of noncomplicated cases). In conclusion, B. cereus bacteraemia can have a complicated course in a subset of patients, mainly those with haematologic malignancy. Catheter infection may be associated with a worse outcome with frequent neurologic complications.

Published
2016
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42. A retrospective study of deep sternal wound infections: clinical and microbiological characteristics, treatment, and risk factors for complications.

Author

Chan M, Yusuf E, Giulieri S, Perrottet N, Von Segesser L, Borens O, and Trampuz A

Subjects
Aged, Aged, 80 and over, Cardiac Surgical Procedures adverse effects, Comorbidity, Female, Humans, Male, Middle Aged, Postoperative Complications, Retrospective Studies, Risk Factors, Wound Infection diagnosis, Wound Infection therapy, Sternum microbiology, Wound Infection epidemiology, Wound Infection etiology
Abstract

Deep sternal wound infection (DSWI) is a feared complication following cardiac surgery. This study describes clinical, microbiological, and treatment outcomes of DSWI and determines risk factors for complications. Of 55 patients with DSWI, 66% were male and mean age was 68.2 years. Initial sternotomy was for coronary artery bypass graft in 49% of patients. Sternal debridement at mean 25.4±18.3 days showed monomicrobial (94%), mainly Gram-positive infection. Secondary sternal wound infection (SSWI) occurred in 31% of patients, was mostly polymicrobial (71%), and was predominantly due to Gram-negative bacilli. Risk factors for SSWI were at least 1 revision surgery (odds ratio [OR] 4.8 [95% confidence interval {CI} 1.0-22.4], P=0.047), sternal closure by muscle flap (OR 4.6 [1.3-16.8], P=0.02), delayed sternal closure (mean 27 versus 14 days, P=0.03), and use of vacuum-assisted closure device (100% versus 58%, P=0.008). Hospital stay was significantly longer in patients with SSWI (69 days versus 48 days, P=0.04)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Published
2016
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43. Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy.

Author

Asner SA, Giulieri S, Diezi M, Marchetti O, and Sanglard D

Subjects
Amino Acid Sequence, DNA, Fungal genetics, Drug Monitoring, Female, Galactose analogs & derivatives, Humans, Immunocompromised Host, Infant, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute drug therapy, Mannans metabolism, Microbial Sensitivity Tests, Molecular Sequence Data, Mutation genetics, Polymorphism, Restriction Fragment Length, beta-Glucans metabolism, Antifungal Agents therapeutic use, Candida drug effects, Candidiasis drug therapy, Candidiasis microbiology, Drug Resistance, Multiple, Fungal genetics
Abstract

Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC [μg/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [μg/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [μg/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and CAS initially followed by azoles alone for a week; P4 (CAS MIC [μg/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [μg/ml], 0.125; CAS MIC, 8), while the patient was being treated with AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5-flurocytosine. This clinical report describes resistance of C. lusitaniae to all common antifungals. While candins or azole resistance followed monotherapy, multidrug antifungal resistance emerged during combined therapy., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Published
2015
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44. Sepsis: a roadmap for future research.

Author

Cohen J, Vincent JL, Adhikari NK, Machado FR, Angus DC, Calandra T, Jaton K, Giulieri S, Delaloye J, Opal S, Tracey K, van der Poll T, and Pelfrene E

Subjects
Clinical Trials as Topic, Disease Management, Forecasting, Host-Pathogen Interactions, Humans, Incidence, Precision Medicine, Sepsis diagnosis, Sepsis epidemiology, Sepsis microbiology, Anti-Bacterial Agents therapeutic use, Biomedical Research trends, Immunologic Factors therapeutic use, Molecular Targeted Therapy, Sepsis drug therapy
Abstract

Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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45. Cryptococcus neoformans meningitis with negative cryptococcal antigen: Evaluation of a new immunochromatographic detection assay.

Author

Opota O, Desgraz B, Kenfak A, Jaton K, Cavassini M, Greub G, Prod'hom G, and Giulieri S

Abstract

Detection of cryptococcal antigen in serum or cerebrospinal fluid allows cryptococcal meningitis diagnosis within few hours with >90% sensitivity. In an HIV-positive patient with Cryptococcus neoformans meningitis, initial antigen detection by immunoagglutination was negative. We thus evaluated a new immunochromatographic detection assay that exhibited a higher sensitivity.

Published
2014
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46. [Clostridial colitis: diagnosis and strategies for management].

Author

Gié O, Clerc D, Giulieri S, and Demartines N

Subjects
Anti-Bacterial Agents therapeutic use, Clostridioides difficile physiology, Diarrhea microbiology, Digestive System Surgical Procedures, Enterocolitis, Pseudomembranous complications, Humans, Postoperative Care, Enterocolitis, Pseudomembranous diagnosis, Enterocolitis, Pseudomembranous drug therapy
Abstract

C. difficile is transmitted in a faecal-oral mode and is widespread in hospital environment. Symptoms of Clostridial infection range from asymptomatic carriage to life-threatening toxic colitis. The treatment of a Clostridial infection is dependent on the seriousness of the symptoms. The diagnosis of the pathogen as well as the introduction of an efficient antibiotic therapy is crucial. Oral metronidazole is the gold standard in treatment of mild infection. Vancomycin should be introduced only in refractory cases or in particular situations. While there is a desire to avoid colectomy, inappropriate delay in a very ill patient can be fatal. Judgement on when to intervene is difficult and requires analysis of the factors which predict outcome with and without surgery. A total abdominal colectomy sparing the rectum with end ileostomy is the procedure of choice.

Published
2014

47. [Skin infections due to rapid-growing mycobacteria].

Author

Gervais P, Manuel O, Jaton K, and Giulieri S

Subjects
Adult, Aged, 80 and over, Anti-Bacterial Agents therapeutic use, Debridement, Female, Humans, Male, Middle Aged, Mycobacterium Infections diagnosis, Skin Diseases, Bacterial diagnosis, Mycobacterium Infections therapy, Skin Diseases, Bacterial microbiology, Skin Diseases, Bacterial therapy
Abstract

Rapid-growing mycobacteria (e.g. M. abscessus and M. chelonae) are emerging pathogens with various clinical manifestations. Among immunocompetent individuals, rapid-growing mycobacteria may be responsible of pulmonary, cutaneous, osteoarticular and postoperative infections, as well as lymphadenitis and catheter-associated infections. Among immunocompromised patients, disseminated infections are also observed. Diagnosis relies on specific microbiological investigations to confirm etiology and guide antibiotic treatment. The treatment requires a multi-disciplinary approach that includes specific long-term antibiotic treatment, surgical debridement and reduction of immunosuppression whenever possible.

Published
2014

48. Cerebral nocardiosis mimicking multiple brain metastases in a patient with locally advanced non-small-cell lung cancer.

Author

Voide C, Zimmermann S, Adjei AA, Betticher DC, Meuli R, Prod'hom G, Giulieri S, and Peters S

Subjects
Aged, Brain Neoplasms drug therapy, Carcinoma, Non-Small-Cell Lung drug therapy, Diagnosis, Differential, Fatal Outcome, Humans, Lung Neoplasms drug therapy, Male, Nocardia Infections drug therapy, Nocardia Infections microbiology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Brain Neoplasms secondary, Carcinoma, Non-Small-Cell Lung diagnosis, Lung Neoplasms diagnosis, Nocardia pathogenicity, Nocardia Infections diagnosis
Published
2014
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49. [Infectious diseases].

Author

Voide C, Asner S, Giulieri S, Cavassini M, Merz L, Tissot F, and Orasch C

Subjects
China epidemiology, Drug Contamination, Drug Resistance, Microbial, Gonorrhea drug therapy, Gonorrhea microbiology, Humans, Influenza A Virus, H7N9 Subtype, Influenza, Human epidemiology, Influenza, Human virology, Mycoses etiology, United States epidemiology, Communicable Diseases, Emerging epidemiology, Communicable Diseases, Emerging etiology, Communicable Diseases, Emerging therapy
Abstract

The recommendations for the treatment of gonorrhea have been changed: ceftriaxone 500 mg IM plus azithromycin 1 g PO is recommended. Prophylaxis of recurrent cellulitis with penicillin 250 mg 2 x/d PO may be considered. E. coli ESBL does not require contact isolation anymore. Fecal transplantation seems so far to be the most effective treatment of recurrent C. dificile. Two new respiratory viruses, Middle East Coronavirus (MERS-CoV) and avian-origin Influenza A (H7N9) have been reported. Oral valganciclovir treatment reduces the risk of hearing loss in congenital CMV infection. An outbreak of mould infections of the central nervous system has been described in the United States following injection of contaminated steroids.

Published
2014

50. Fluorescein and indocyanine-green angiography in ocular syphilis: an exploratory study.

Author

Balaskas K, Sergentanis TN, Giulieri S, and Guex-Crosier Y

Subjects
Adult, Ceftriaxone therapeutic use, Eye Infections, Bacterial drug therapy, Female, Humans, Injections, Intravenous, Male, Middle Aged, Penicillins therapeutic use, Retrospective Studies, Syphilis drug therapy, Syphilis microbiology, Syphilis Serodiagnosis, Uveitis drug therapy, Uveitis microbiology, Coloring Agents, Eye Infections, Bacterial diagnosis, Fluorescein Angiography, Indocyanine Green, Syphilis diagnosis, Uveitis diagnosis
Abstract

Background: Fluorescein (FA) and indocyanine-green angiography (ICGA) may offer valuable information concerning disease severity and prognosis in ocular syphilis. The aim of the present study is to describe angiographic patterns encountered in the context of ocular syphilis, and to explore the associations between specific angiographic manifestations and severity of disease presentation, as well as disease evolution after treatment., Methods: We performed a retrospective institutional study with the inclusion of 23 patients with ocular syphilis presenting to the uveitis clinic of the Jules-Gonin Eye Hospital in a 10-year period. FA and ICGA were performed following a standard protocol for posterior uveitis. Patterns of fluorescence were noted, and statistical associations between each angiographic pattern and any demographic, clinical, or laboratory parameter at baseline and after treatment were sought., Results: The presence of any dark dots in ICGA was significantly associated with anterior uveitis (p = 0.031). The presence of hot spots in ICGA was significantly associated with longer duration of symptoms prior to initial visit (p = 0.032) and with male gender (p = 0.012). Weak non-significant trends were found associating vascular staining in FA with anterior uveitis (p = 0.066), vitritis (p = 0.069), and younger age (p = 0.061), as well as disc hyperfluorescence in FA with seropositivity for HIV (p = 0.089) and macular edema in FA with longer disease duration (p = 0.061). The presence of any dark dots in ICGA exhibited a weak trend of association with anterior uveitis and/or vitritis (p = 0.079)., Conclusions: Out of the several associations identified implicating specific angiographic features, we underline the possible role of the presence of dark dots in ICGA for identifying active inflammation, and the role of hot spots in ICGA as markers of long-standing disease. Vascular staining in FA appears to be more common in patients with severe ocular inflammation with presence of anterior uveitis and/or vitritis.

Published
2012
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