Phenotypic and genotypic discrepancies for carbapenemase-producing Citrobacter freundii in multiple isolates from a single patient.

BACKGROUND: Carbapenemase-producing gram-negative organisms continue to be a significant healthcare concern and a therapeutic challenge. Members of the genus Citrobacter have emerged as increasingly multidrug resistant and versatile healthcare-associated pathogens. In this study we investigated five KPC-producing Citrobacter freundii isolates, from the same patient, that presented unusual phenotypic characteristics including false susceptibility to carbapenems detection by culture-based methods. METHODS: The isolates were tested for antimicrobial susceptibility using broth microdilution and disk diffusion. Production of serine carbapenemase was confirmed with the mCIM (modified carbapenem inactivation method) test. Genotypes were determined by PCR and whole genome sequencing analysis. RESULTS: The five isolates were susceptible to meropenem by broth microdilution and presented varying colonial morphologies and levels of susceptibility to carbapenems by multiple phenotypic methods, despite being positive for carbapenemase production by mCIM and positive for blaKPC by PCR. Whole genome sequence analysis showed that three of the five highly related isolates harbor an additional gene cassette, including blaCARB-2, ant(2''), aadA2, dfrA19, catB3, cmlA1, mph(E), msr(E), and qnrA1. The presence of these genes explains the difference in phenotypes observed. CONCLUSION: Failure to detect and completely eradicate the carbapenemase-producing C. freundii in the urine with ertapenem therapy, likely due to the presence of a heterogeneous population, resulted in the phenotypic and genotypic adaptations of the organism as it disseminated to the bloodstream and kidneys. The fact that carbapenemase-producing C. freundii can elude detection by phenotypic methods and can so easily acquire and transfer resistance gene cassettes is of concern.

Proceedings of the Clinical Microbiology Open 2018 and 2019 - a Discussion about Emerging Trends, Challenges, and the Future of Clinical Microbiology.

Clinical Microbiology Open (CMO), a meeting supported by the American Society for Microbiology's Clinical and Public Health Microbiology Committee (CPHMC) and Corporate Council, provides a unique interactive platform for leaders from diagnostic microbiology laboratories, industry, and federal agencies to discuss the current and future state of the clinical microbiology laboratory. The purpose is to leverage the group's diverse views and expertise to address critical challenges, and discuss potential collaborative opportunities for diagnostic microbiology, through the utilization of varied resources. The first and second CMO meetings were held in 2018 and 2019, respectively. Discussions were focused on the diagnostic potential of innovative technologies and laboratory diagnostic stewardship, including expansion of next-generation sequencing into clinical diagnostics, improvement and advancement of molecular diagnostics, emerging diagnostics, including rapid antimicrobial susceptibility and point of care testing (POCT), harnessing big data through artificial intelligence, and staffing in the clinical microbiology laboratory. Shortly after CMO 2019, the coronavirus disease 2019 (COVID-19) pandemic further highlighted the need for the diagnostic microbiology community to work together to utilize and expand on resources to respond to the pandemic. The issues, challenges, and potential collaborative efforts discussed during the past two CMO meetings proved critical in addressing the COVID-19 response by diagnostic laboratories, industry partners, and federal organizations. Planning for a third CMO (CMO 2022) is underway and will transition from a discussion-based meeting to an action-based meeting. The primary focus will be to reflect on the lessons learned from the COVID-19 pandemic and better prepare for future pandemics.

2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients.

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.

Clostridium perfringens empyema in a patient with metastatic squamous cell carcinoma of the lung.

We report a rare case of Clostridium perfringens (CP) empyema in a patient with metastatic squamous cell cancer of the lung. Clostridial empyemas are rare and clinically variable with some reports noting consequent necrotizing infections and septic shock and others noting quick resolution with source control and antibiotic treatment. This is the first case report to our knowledge to report a CP empyema in a patient with lung malignancy. Given the comorbid lung malignancy, the patient's presenting symptoms were mild with only mild shortness of breath, fevers, and generalized weakness despite the large CP empyema. Early antibiotics and source control with daily drainage of the pleural fluid allowed for successful management, circumventing a complex critical care course and successful management without ambulatory oxygen therapy on discharge.

Clostridium difficile Screening for Colonization During an Outbreak Setting.

A rapidly deployed ward-based screen and isolate initiative for Clostridium difficile carriers during an outbreak averted 5 of 10 expected hospital-acquired infections without identified harms. Each infection avoided required screening 197 and isolating 4.4 patients. Targeted C. difficile screening resulted in outbreak mitigation.

Waltzing around Sacred Cows on the Way to the Future.

Our mostly manual, agar-based clinical microbiology laboratory is slowly but steadily being redefined by automation and innovation. Ironically, the oldest test, the Gram stain test, is still manually read and interpreted by trained personnel. In a proof-of-concept study, Smith et al. (J. Clin. Microbiol. 56:e01521-17, 2018, https://doi.org/10.1128/JCM.01521-17) used computer imaging with a deep convolutional neural network to examine and interpret Gram-stained slides from positive blood culture bottles. In light of the shortage of medical technologists/microbiologists and the need for results from positive blood culture bottles 24/7, this paper paves the way for the next innovations for the clinical microbiology laboratory of the future.

The Global Alliance for Infections in Surgery: defining a model for antimicrobial stewardship-results from an international cross-sectional survey.

BACKGROUND: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. METHODS: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. RESULTS: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p < 0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). CONCLUSION: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

Complicated Urinary Tract Infections: What's a Lab To Do?

The article by Price et al. in this issue (T. K. Price et al., J Clin Microbiol 54:1216-1222, 2016, http://dx.doi.org/10.1128/JCM.00044-16) advocates for the use of a larger inoculum when culturing urine obtained by "in-and-out" catheterization in a selected female population. Their findings and the resulting challenges will afford clinical microbiologists and specialty physicians an opportunity to review what will or should be done with the additional microbiological culture data.

Culture if spikes? Indications and yield of blood cultures in hospitalized medical patients.

BACKGROUND: Although optimal utilization of blood cultures has been studied in populations, including emergency room and intensive care patients, less is known about the use of blood cultures in populations consisting exclusively of patients on a medical service. OBJECTIVE: To identify the physician-selected indication and yield of blood cultures ordered after hospitalization to an acute medical service and to identify populations in which blood cultures may not be necessary. DESIGN, SETTING, AND PATIENTS: A prospective cohort study was performed at a single Veterans Affairs Medical Center from October 1, 2014 through April 15, 2015. Participants included all hospitalized patients on a medical service for whom a blood culture was ordered. MEASUREMENTS: The main outcomes were the rate of true positive blood cultures and the predictors of true positive cultures. RESULTS: The true positive rate was 3.6% per order. The most common physician-selected indications were fever and leukocytosis, neither of which alone was highly predictive of true positive blood cultures. The only indication significantly associated with a true positive blood culture was "follow-up previous positive" (likelihood ratio [LR]+ 3.4, 95% confidence interval [CI]: 1.8-6.5). The only clinical predictors were a working diagnosis of bacteremia/endocarditis (LR+ 3.7, 95% CI: 2.5-5.7) and absence of antibiotic exposure within 72 hours of the culture (LR+ 2.4, 95% CI: 1.2-4.9). CONCLUSIONS: The rate of true positive blood cultures among patients on a medical service was lower than previously studied. Using objective and easily obtainable clinical characteristics, including antibiotic exposure and working diagnosis, may improve the likelihood of true positive blood cultures. Journal of Hospital Medicine 2016;11:336-340. © 2016 Society of Hospital Medicine.

Activity of Fosfomycin against Extended-Spectrum-ß-Lactamase-Producing Uropathogens in Patients in the Community and Hospitalized Patients.

Few oral antibiotics exist for the empirical treatment of extended-spectrum ß-lactamase (ESBL) urinary tract infections (UTI). In this study, we sought to determine the activity of fosfomycin against ESBL-producing uropathogens from patients at 3 Veterans Affairs (VA) facilities between 2010 and 2013. Among the ESBL uropathogens, 19.9% were fosfomycin resistant. Klebsiella species were more likely than Escherichia coli to be resistant (46% versus 4%; P < 0.001). Fosfomycin remains active against a majority of the ESBL uropathogens, although resistance among Klebsiella spp. was higher than that in previous reports.

WSES guidelines for management of Clostridium difficile infection in surgical patients.

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

First report of Mycobacterium canariasense catheter-related bacteremia in the Americas.

Mycobacterium canariasense is a recently described late-pigmenting, rapidly growing mycobacterium linked to bacteremia in patients with underlying malignant diseases. We report a case of M. canariasense infection in a patient from Massachusetts with underlying diffuse B cell lymphoma, which was identified both by multilocus sequence typing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). To our knowledge, this is the first description after its original identification in Spain and the first report of this opportunistic pathogen in the Americas.

Laboratory diagnosis of Clostridium difficile infections: there is light at the end of the colon.

Single molecular or multistep assays (glutamate dehydrogenase, toxin A/B, ± molecular) are recommended for the diagnosis of CDI in patients with clinically significant diarrhea. Rapid and accurate tests can improve resource allocations and improve patient care. Enzyme immunoassay (EIA) for toxins A/B is too insensitive for use as a stand-alone assay. This guideline will examine the use of molecular tests and multitest algorithms for the diagnosis of Clostridium difficile infection (CDI). These new tests, alone or in a multistep algorithm consisting of >1 assay, are more expensive than the older EIA assays; however, rapid and accurate testing can save money overall by initiating appropriate treatment and infection control protocols sooner and by possibly reducing length of hospital stay. We recommend testing only unformed stool in patients with clinically significant diarrhea by a molecular method or by a 2- to 3-step algorithm.

Clostridium difficile ribotype diversity at six health care institutions in the United States.

Capillary-based PCR ribotyping was used to quantify the presence/absence and relative abundance of 98 Clostridium difficile ribotypes from clinical cases of disease at health care institutions in six states of the United States. Regionally important ribotypes were identified, and institutions in close proximity did not necessarily share more ribotype diversity than institutions that were farther apart.

Has the emergence of community-associated methicillin-resistant Staphylococcus aureus increased trimethoprim-sulfamethoxazole use and resistance?: a 10-year time series analysis.

There are an increasing number of indications for trimethoprim-sulfamethoxazole use, including skin and soft tissue infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Assessing the relationship between rates of use and antibiotic resistance is important for maintaining the expected efficacy of this drug for guideline-recommended conditions. Using interrupted time series analysis, we aimed to determine whether the 2005 emergence of CA-MRSA and recommendations of trimethoprim-sulfamethoxazole as the preferred therapy were associated with changes in trimethoprim-sulfamethoxazole use and susceptibility rates. The data from all VA Boston Health Care System facilities, including 118,863 inpatient admissions, 6,272,661 outpatient clinic visits, and 10,138 isolates were collected over a 10-year period. There was a significant (P = 0.02) increase in trimethoprim-sulfamethoxazole prescriptions in the post-CA-MRSA period (1,605/year) compared to the pre-CA-MRSA period (1,538/year). Although the overall susceptibility of Escherichia coli and Proteus spp. to trimethoprim-sulfamethoxazole decreased over the study period, the rate of change in the pre- versus the post-CA-MRSA period was not significantly different. The changes in susceptibility rates of S. aureus to trimethoprim-sulfamethoxazole and to methicillin were also not significantly different. The CA-MRSA period is associated with a significant increase in use of trimethoprim-sulfamethoxazole but not with significant changes in the rates of susceptibilities among clinical isolates. There is also no evidence for selection of organisms with increased resistance to other antimicrobials in relation to increased trimethoprim-sulfamethoxazole use.