<strong>Pan-Echinocandin-Resistant <em>Candida glabrata</em> Bloodstream Infection Complicating COVID-19: A Fatal Case Report</strong>

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, but coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly due to multidrug-resistant Gram-negative bacteria, and lastly due to a possibly fatal Candida glabrata. The development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

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Trends of Bloodstream Infections in a University Greek Hospital during a Three-Year Period: Incidence of Multidrug-Resistant Bacteria and Seasonality in Gram-negative Predominance

Polish Journal of Microbiology ◽

10.5604/01.3001.0010.7834 ◽

2017 ◽

Vol 66 (2) ◽

pp. 171-180 ◽

Cited By ~ 14

Author(s):

Fevronia Kolonitsiou ◽

Matthaios Papadimitriou-Olivgeris ◽

Anastasia Spiliopoulou ◽

Vasiliki Stamouli ◽

Vasileios Papakostas ◽

...

Keyword(s):

Bloodstream Infections ◽

Multidrug Resistant ◽

Blood Cultures ◽

Diffusion Method ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Multidrug Resistant Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Carbapenem Resistant

The aim of the study was to assess the epidemiology, the incidence of multidrug-resistant bacteria and bloodstream infections’ (BSIs) seasonality in a university hospital. This retrospective study was carried out in the University General Hospital of Patras, Greece, during 2011–13 y. Blood cultures from patients with clinical presentation suggestive of bloodstream infection were performed by the BacT/ALERT System. Isolates were identified by Vitek 2 Advanced Expert System. Antibiotic susceptibility testing was performed by the disk diffusion method and E-test. Resistance genes (mecA in staphylococci; vanA/vanB/vanC in enterococci; blaKPC/blaVIM/blaNDM in Klebsiella spp.) were detected by PCR. In total, 4607 (9.7%) blood cultures were positive from 47451 sets sent to Department of Microbiology, representing 1732 BSIs. Gram-negative bacteria (52.3%) were the most commonly isolated, followed by Gram-positive (39.5%), fungi (6.6%) and anaerobes bacteria (1.8%). The highest contamination rate was observed among Gram-positive bacteria (42.3%). Among 330 CNS and 150 Staphylococcus aureus, 281 (85.2%) and 60 (40.0%) were mecA-positive, respectively. From 113 enterococci, eight were vanA, two vanB and two vanC-positives. Of the total 207 carbapenem-resistant Klebsiella pneumoniae (73.4%), 202 carried blaKPC, four blaKPC and blaVIM and one blaVIM. A significant increase in monthly BSIs’ incidence was shown (R2: 0.449), which may be attributed to a rise of Gram-positive BSIs (R2: 0.337). Gram-positive BSIs were less frequent in spring (P < 0.001), summer (P < 0.001), and autumn (P < 0.001), as compared to winter months, while Gram-negative bacteria (P < 0.001) and fungi (P < 0.001) were more frequent in summer months. BSIs due to methicillin resistant S. aureus and carbapenem-resistant Gram-negative bacteria increased during the study period. The increasing incidence of BSIs can be attributed to an increase of Gram-positive BSI incidence, even though Gram-negative bacteria remained the predominant ones. Seasonality may play a role in the predominance of Gram-negative’s BSI.

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Role of FKS Mutations in Candida glabrata: MIC Values, Echinocandin Resistance, and Multidrug Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03255-14 ◽

2014 ◽

Vol 58 (8) ◽

pp. 4690-4696 ◽

Cited By ~ 127

Author(s):

Cau D. Pham ◽

Naureen Iqbal ◽

Carol B. Bolden ◽

Randall J. Kuykendall ◽

Lee H. Harrison ◽

...

Keyword(s):

Candida Glabrata ◽

Susceptibility Testing ◽

Hot Spot ◽

Case Reports ◽

Multidrug Resistant ◽

High Rate ◽

Primary Therapy ◽

Content Type ◽

Major Mechanism ◽

Echinocandin Resistance

ABSTRACTCandida glabratais the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment ofC. glabratadisease due to the high rate of resistance to fluconazole. Recent case reports indicate thatC. glabrataresistance to echinocandins may be increasing. We performed susceptibility testing on 1,380 isolates ofC. glabratacollected between 2008 and 2013 from four U.S. cities, Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and micafungin, respectively. We screened 1,032 of these isolates, including all 77 that had either a resistant or intermediate MIC value with respect to at least one echinocandin, for mutations in the hot spot regions ofFKS1andFKS2, the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hot spot mutations, 16 inFKS1and 35 inFKS2. All of the isolates with anFKSmutation except one were resistant to at least one echinocandin by susceptibility testing. Of the isolates resistant to at least one echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among U.S.C. glabrataisolates is a concern, especially in light of the fact that one-third of those isolates may be multidrug resistant. Further monitoring of U.S.C. glabrataisolates for echinocandin resistance is warranted.

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Bacteria drug resistance profile affects knee and hip periprosthetic joint infection outcome with debridement, antibiotics and implant retention

10.21203/rs.2.20884/v2 ◽

2020 ◽

Author(s):

Bruno Alves Rudelli ◽

Pedro Nogueira Giglio ◽

Vladimir Cordeiro Carvalho ◽

Jose Ricardo Pecora ◽

Henrique Melo Campos Gurgel ◽

...

Keyword(s):

Treatment Failure ◽

Failure Rate ◽

Methicillin Resistant Staphylococcus Aureus ◽

Multidrug Resistant ◽

The Other ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Treatment Failure Rate ◽

Drug Resistance Profile ◽

Implant Retention

Abstract BACKGROUND: evaluate the effect of bacteria drug resistance profile on the success rates of debridement, antibiotics and implant retention. METHODS: All early acute periprosthetic infections in hip and knee arthroplasties treated with DAIR at our institution over the period from 2011 to 2015 were retrospectively analyzed. The success rate was evaluated according to the type of organism identified in culture: multidrug-sensitive (MSB), methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Gram-negative bacteria (MRB) and according to other risk factors for treatment failure. The data were analyzed using univariate and multivariate statistics. RESULTS: Fifty-seven patients were analyzed; there were 37 in the multidrug-sensitive bacteria (MSB) group, 11 in the methicillin-resistant Staphylococcus aureus (MRSA) group and 9 in the other multidrug-resistant Gram-negative bacteria (MRB) group. There was a statistically significant difference (p<0.05) in the treatment failure rate among the three groups: 8.3% for the MSB group, 18.2% for the MRSA group and 55.6% for the MRB group (p=0.005). Among the other risk factors for treatment failure, the presence of inflammatory arthritis presented a failure rate of 45.1 (p<0.05). CONCLUSION: DAIR showed a good success rate in cases of early acute infection by multidrug-sensitive bacteria. In the presence of infection by multidrug-resistant bacteria or association with rheumatic diseases the treatment failure rate was higher and other surgical options should be considered in this specific population. The MRSA group showed intermediate results between MSB and MRB and should be carefully evaluated.

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Abdominal Candidiasis Is a Hidden Reservoir of Echinocandin Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04134-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7601-7605 ◽

Cited By ~ 51

Author(s):

Ryan K. Shields ◽

M. Hong Nguyen ◽

Ellen G. Press ◽

Cornelius J. Clancy

Keyword(s):

Candida Albicans ◽

Candida Glabrata ◽

Multidrug Resistant ◽

Source Control ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

Content Type ◽

Echinocandin Resistance ◽

Abdominal Candidiasis

ABSTRACTFKSmutantCandidaisolates were recovered from 24% (6/25) of abdominal candidiasis patients exposed to echinocandin.Candida glabrata(29%) andCandida albicans(14%) mutants were identified. Multidrug-resistant bacteria were recovered from 83% ofFKSmutant infections. Mutations were associated with prolonged echinocandin exposure (P= 0.01), breakthrough infections (P= 0.03), and therapeutic failures despite source control interventions (100%). Abdominal candidiasis is a hidden reservoir for the emergence of echinocandin-resistantCandida.

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Neonate Bloodstream Infections (BSI) in China: Emerging Threat of Multidrug-resistant (MDR) pathogens

10.21203/rs.3.rs-46747/v1 ◽

2020 ◽

Author(s):

hua zou ◽

Ligang Zhou ◽

Yan Shen ◽

Chunli Li ◽

Qiuhong Li

Keyword(s):

Early Onset ◽

Pathogenic Bacteria ◽

Late Onset ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Multi Drug Resistance ◽

Gram Negative Bacteria ◽

Antibiotic Exposure ◽

Gram Negative ◽

E Coli

Abstract Background: Bloodstream Infections (BSIs) continue to be associated with significant morbidity and mortality worldwide, which multidrug-resistant (MDR) pathogens present an ever-growing burden in the hospital and community settings. Data on antimicrobial resistance and prevalence of BSIs pathogens among hospitalized neonates in China are few and not clearly defined. Methods: we retrospectively collected clinical and bacteria data about patients with BSI from 2013 to 2017 in Chongqing Health Center for Women and Children. The patients were divided into the early- and late-onset BSI groups according to if BSI occurred within or beyond 72 hours after admission.Results: 210 BSIs occurred from January 1st, 2014 to December 31th, 2019. Of all included 210 patients, there were 99(47.14%), 105 (50.00%), and 6 (2.86%) infected with gram-positive bacteria, gram-negative bacteria, and fungi, respectively. For early-onset BSI, the predominated pathogen was E. coli, accounting for 59.6% with 29.72% producing of extended-spectrum beta-lactamases (ESBLs). CNS (40.3%), K. pneumoniae (23.8%), and E. coli (20.9%) constitute the main causes of late-onset BSIs. Notably, 75.0% of K. pneumoniae produced ESBLs and 81.3% were MDR, which were higher than early-onset BSIs. Late onset BSIs and antibiotic exposure were significantly associated with MDR infection. Conclusion: Gram-negative bacteria gradually became the main pathogenic bacteria, among which E. coli and K. pneumoniae accounted for the largest proportion. The phenomenon of multi-drug resistance of bacteria is serious, and the first-line drug can't meet the practical needs. Late onset sepsis and antibiotic exposure were significantly associated with MDR infection.

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Ceftazidime/Avibactam and Ceftolozane/Tazobactam for Multidrug-Resistant Gram Negatives in Patients with Hematological Malignancies: Current Experiences

Antibiotics ◽

10.3390/antibiotics9020058 ◽

2020 ◽

Vol 9 (2) ◽

pp. 58 ◽

Cited By ~ 2

Author(s):

Marianna Criscuolo ◽

Enrico Maria Trecarichi

Keyword(s):

Hematological Malignancies ◽

Real Life ◽

Bloodstream Infections ◽

Multidrug Resistant ◽

Infectious Complications ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Life Threatening ◽

Severe Infections ◽

Tract Infections

Patients suffering from hematological malignancies are at high risk for severe infections, including in particular bloodstream infections, which represent one of the most frequent life-threatening complications for these patients, with reported mortality rates reaching 40%. Furthermore, a worrisome increase in antimicrobial resistance of Gram-negative bacteria (e.g., cephalosporin- and/or carbapenem-resistant Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa) involved in severe infectious complications among patients with hematological malignancies has been reported during the last years. The two novel combination of cephalosporins and β-lactamase inhibitors, ceftolozane/tazobactam and ceftazidime/avibactam, were recently approved for treatment of complicated intra-abdominal and urinary tract infections and nosocomial pneumonia and display activity against several MDR Gram-negative strains. Although not specifically approved for neutropenic and/or cancer patients, these drugs are used in this setting due to increasing rates of infections caused by MDR Gram-negative bacteria. The aim of this review is to describe the actual evidence from scientific literature about the “real-life” use of these two novel drugs in patients with hematological malignancies and infections caused by MDR Gram-negative bacteria.

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Bacteria drug resistance profile affects knee and hip periprosthetic joint infection outcome with debridement, antibiotics and implant retention

10.21203/rs.2.20884/v1 ◽

2020 ◽

Author(s):

Bruno Alves Rudelli ◽

Pedro Nogueira Giglio ◽

Vladimir Cordeiro Carvalho ◽

Jose Ricardo Pecora ◽

Henrique Melo Campos Gurgel ◽

...

Keyword(s):

Treatment Failure ◽

Failure Rate ◽

Methicillin Resistant Staphylococcus Aureus ◽

Multidrug Resistant ◽

The Other ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Treatment Failure Rate ◽

Drug Resistance Profile ◽

Implant Retention

Abstract BACKGROUND: evaluate the effect of bacteria drug resistance profile on the success rates of debridement, antibiotics and implant retention. METHODS: All early acute periprosthetic infections in hip and knee arthroplasties treated with DAIR at our institution over the period from 2011 to 2015 were retrospectively analyzed. The success rate was evaluated according to the type of organism identified in culture: multidrug-sensitive (MSB), methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Gram-negative bacteria (MRB) and according to other risk factors for treatment failure. The data were analyzed using univariate and multivariate statistics. RESULTS: Fifty-seven patients were analyzed; there were 37 in the multidrug-sensitive bacteria (MSB) group, 11 in the methicillin-resistant Staphylococcus aureus (MRSA) group and 9 in the other multidrug-resistant Gram-negative bacteria (MRB) group. There was a statistically significant difference (p<0.05) in the treatment failure rate among the three groups: 8.3% for the MSB group, 18.2% for the MRSA group and 55.6% for the MRB group (p=0.005). Among the other risk factors for treatment failure, the presence of inflammatory arthritis presented a failure rate of 45.1 (p<0.05). CONCLUSION: DAIR showed a good success rate in cases of early acute infection by multidrug-sensitive bacteria. In the presence of infection by multidrug-resistant bacteria or association with rheumatic diseases the treatment failure rate was higher and other surgical options should be considered in this specific population. The MRSA group showed intermediate results between MSB and MRB and should be carefully evaluated.

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Genetic Basis of Azole and Echinocandin Resistance in Clinical Candida glabrata in Japan

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00783-20 ◽

2020 ◽

Vol 64 (9) ◽

Author(s):

Hazim O. Khalifa ◽

Teppei Arai ◽

Hidetaka Majima ◽

Akira Watanabe ◽

Katsuhiko Kamei

Keyword(s):

Candida Glabrata ◽

Molecular Mechanisms ◽

Hot Spot ◽

Multidrug Resistant ◽

Fungal Resistance ◽

Patient Treatment ◽

Azole Resistance ◽

Nonsynonymous Mutation ◽

Content Type ◽

Echinocandin Resistance

ABSTRACT Infections caused by Candida glabrata have caused worldwide concern, especially when they are associated with increasing echinocandin and azole resistance. In this study, we analyzed the molecular mechanisms of azole and echinocandin resistance in C. glabrata isolates obtained from hospitalized patients in Japan from 1997 to 2019. All isolates were checked phenotypically for resistance and genotypically for mutations in PDR1, ERG11, hot spot 1 (HS1), HS2, and HS3 of FKS1, and HS1 and HS2 of FKS2, and all isolates were genotyped by multilocus sequence typing (MLST). Interestingly, 32.6% of the isolates were resistant to caspofungin, and 4.7% were resistant to micafungin. The isolates showed low rates of resistance to azoles, ranging from 2.3% to 9.3%, and only 4.7% of the isolates were non-wild type for flucytosine susceptibility. For the first time in Japan, 4.7% of the isolates were identified as multidrug-resistant strains. Nonsynonymous mutations in PDR1, including two novel mutations associated with azole resistance, were identified in 39.5% of the isolates, and a single nonsynonymous mutation was identified in ERG11. Nine isolates from the same patient harbored nonsynonymous mutations in HS1 of FKS2, and a single isolate harbored a single nonsynonymous mutation in HS1 of FKS1. MLST genotyping revealed 13 different sequence types (STs), with 3 new STs, and ST7 was the most prevalent among the patients (35%) and was associated with high resistance rates. Our results are of crucial clinical concern, since understanding the molecular mechanisms underlying fungal resistance is imperative for guiding specific therapy for efficient patient treatment and promoting strategies to prevent epidemic spread.

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Management of meningitis caused by multi drug-resistant Acinetobacter baumannii: clinical, microbiological and pharmacokinetic results in a patient treated with colistin methanesulfonate

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2015.055 ◽

2015 ◽

Vol 7 ◽

pp. e201555 ◽

Cited By ~ 3

Author(s):

Elisabetta Schiaroli ◽

Maria Bruna Pasticci ◽

Maria Iris Cassetta ◽

Stefania Fallani ◽

Corrado Castrioto ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Acinetobacter Baumannii ◽

Methicillin Resistant Staphylococcus Aureus ◽

Clinical Course ◽

Gram Negative Bacteria ◽

Drug Resistant ◽

Fluid Accumulation ◽

Cerebrospinal Fluid Rhinorrhea ◽

Extensively Drug Resistant ◽

Colistin Methanesulfonate

This paper reports on a 71-year-old Caucasian male who underwent neurosurgery for an oligodendroglioma, followed by a cranial-sinus fistula and cerebrospinal fluid rhinorrhea. The clinical course was complicated due to an extensively drug-resistant Acinetobacter baumannii meningitis. The patient was treated with colistin methanesulfonate, intrathecal for 24 days and intravenous for 46 days. In addition, the patient received meropenem and teicoplanin to treat a bacterial aspiration pneumonia, probably caused by methicillin resistant Staphylococcus aureus and multi drug-resistant Klebiesella pneumoniae. Cerebrospinal fluid trough colistin levels resulted above the MIC of A. baumannii. Colistin cerebrospinal fluid accumulation over the treatment period was not reported. Meningitis was cured and A. baumannii eradicated. No side effects from the antimicrobial therapy were observed.In conclusion, this case highlights the issues in treating infections caused by resistant Gram-negative bacteria and supports previous findings on the efficacy, pharmacokinetic and tolerability of intravenous and intrathecal colistin treatments.

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