Seven mobile oxazolidinone resistance genes, including cfr, cfr(B), cfr(C), cfr(D), cfr(E), optrA, and poxtA, have been identified to date. The cfr genes code for 23S rRNA methylases, which confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The optrA and poxtA genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. The optrA gene confers resistance to oxazolidinones and phenicols, while the poxtA gene confers elevated MICs or resistance to oxazolidinones, phenicols, and tetracycline. These oxazolidinone resistance genes are most frequently found on plasmids, but they are also located on transposons, integrative and conjugative elements (ICEs), genomic islands, and prophages. In these mobile genetic elements (MGEs), insertion sequences (IS) most often flanked the cfr, optrA, and poxtA genes and were able to generate translocatable units (TUs) that comprise the oxazolidinone resistance genes and occasionally also other genes. MGEs and TUs play an important role in the dissemination of oxazolidinone resistance genes across strain, species, and genus boundaries. Most frequently, these MGEs also harbor genes that mediate resistance not only to antimicrobial agents of other classes, but also to metals and biocides. Direct selection pressure by the use of antimicrobial agents to which the oxazolidinone resistance genes confer resistance, but also indirect selection pressure by the use of antimicrobial agents, metals, or biocides (the respective resistance genes against which are colocated on cfr-, optrA-, or poxtA-carrying MGEs) may play a role in the coselection and persistence of oxazolidinone resistance genes.

Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria.

Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries the plasmid pAB5, a member of the family of large conjugative plasmids that represses the type VI secretion system (T6SS) in multiple Acinetobacter strains. pAB5 confers niche specificity, as its carriage improves UPAB1 survival in a CAUTI model and decreases virulence in a pneumonia model. Comparative proteomic and transcriptomic analyses show that pAB5 regulates the expression of multiple chromosomally-encoded virulence factors besides T6SS. Our results demonstrate that plasmids can impact bacterial infections by controlling the expression of chromosomal genes.

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Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes

The increasing emergence of Acinetobacter spp. with healthcare associated infections (HCAI) in intensive care units (ICU) is alarming. This study was a laboratory-based audit to determine the prevalence of Acinetobacter spp. associated with HCAI in the adult ICU of a tertiary care hospital in Varanasi, north India, with special reference to antimicrobial resistance and resistance determinants over a period of 5 years. A total of 993 cases of HCAI were analyzed. Isolates were characterized as multidrug resistance and extended drug resistance (MDR/XDR) based on antimicrobial susceptibility records. Few (100) randomly selected isolates of Acinetobacter baumannii (A. baumannii) were tested for imipenem, meropenem, and polymyxin B susceptibility by minimum inhibitory concentration (MIC) and for the presence of class A and B carbapenemases by multiplex PCR. Active surveillance of ICU environment was also performed. High prevalence of Acinetobacter related hospital acquired pneumonia (HAP) with significant resistance to imipenem (p<0.05) and 88.02% MDR and 61.97% XDR was detected along with persistence in the ICU environment. The isolates harbored blaIMP (89%), blaVIM (51%), blaNDM-1 (34%), and blaOXA-23-like (93%) genes. Specific interventional measures should be adopted to control these imipenem resistant Acinetobacter spp. which have attained the level of endemicity in our ICU setup.

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High Prevalence and Endemicity of Multidrug Resistant Acinetobacter spp. in Intensive Care Unit of a Tertiary Care Hospital, Varanasi, India.

Is it necessary to have a dentist within an intensive care unit team?: report of a randomised clinical trial

Ventilator-associated pneumonia (VAP) is one of the most frequent ICU-acquired infections and a leading cause of death among patients in Intensive Care Unit (ICU). The South East Asian Region is a part of the world with limited health resources where infectious diseases are still underestimated. We aimed to review the literature in this part of the world to describe incidence, mortality and microbiological evidence of VAP and explore preventive and control strategies. We selected 24 peer-reviewed articles published from January 1, 2000 to September 1, 2020 from electronic databases and manual searching for observational studies among adult patients diagnosed with VAP expressed per thousand days admitted in ICU. The VAP rates ranged from 2.13 to 116 per thousand days, varying among different countries of this region. A significant rate of mortality was observed in 13 studies ranging from 16.2% to 74.1%. Gram negative organisms like Acinetobacter spp., Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive organisms like Staphylococcus aureus and Enterococcus species were frequently found. Our findings suggest an alarming situation of VAP among patients of most of the countries of this region with increasing incidence, mortality and antibiotic resistance. Thus, there is an urgent need for cost effective control and preventive measures like interventional studies and educational programs on staff training, hand hygiene, awareness on antibiotic resistance, implementation of antibiotic stewardship programs and appropriate use of ventilator bundle approach.

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Ventilator-associated pneumonia among ICU patients in WHO Southeast Asian region: A systematic review

Prospective surveillance of device-associated health care-associated infection in an intensive care unit of a tertiary care hospital in New Delhi, India.

Coagulase-negative Staphylococci (CoNS) have emerged as a major causative agent of blood-stream infections (BSI). Linezolid (LZD) is currently used for treating glycopeptide and methicillin-resistant staphylococci. It is important to understand the resistance mechanism and probable transmission of LZD resistant (LR) CoNS within the hospital. Clinically significant LRCoNS from patients with BSI were characterized using MALDI-TOF and 16S rRNA gene sequence analysis. Antimicrobial susceptibility and MIC of vancomycin and LZD were determined. LZD resistance mechanisms using PCR for the cfr gene and mutation in the V domain of the 23S rRNA gene were studied. The MIC of LZD ranged from 8 to 32 μg/ml. LR was observed in three different CoNS species from diverse locations within the hospital. The cfr gene was identified in all the isolates. Sequence analysis of V domain region of 23S rRNA gene confirmed mutation in single copy among 12/15 isolates with novel mutations: G2614 T and C2384T. All infections were nosocomially acquired and LZD resistance was emerging in the absence of prior LZD use. Horizontal spread of resistant isolates and cfr gene among diverse species were the probable mechanisms of transmission. The study highlights the novel mutations associated with LRCoNS and the importance of surveillance & transmission pathway within the hospital. It also systematically discusses the published information on LRCoNS.

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Linezolid resistant coagulase negative staphylococci (LRCoNS) with novel mutations causing blood stream infections (BSI) in India

Background Procalcitonin, a biomarker to adjudge the duration of antibiotic therapy in patients with sepsis. Materials and methods A prospective, randomized, controlled, interventional, single-center study was conducted in a mixed adult intensive care unit (ICU). In a nonblinded study, 90 adult patients admitted to the ICU with sepsis and septic shock were randomized into group P (group procalcitonin) and group C (group control). The duration of antibiotic therapy was decided based on serum procalcitonin levels for patients in group P versus standard treatment protocols in group C. A procalcitonin value of 80% from the baseline was cutoff and chosen to stop the antibiotic therapy. The primary aim was to compare the duration of antibiotic therapy (in days) in the two groups. The secondary objective was to compare and assess the length of ICU stay, reinfection, secondary infection rate, readmission rate, and mortality among the groups. Results The mean duration of antibiotic therapy was significantly lesser in patients in group P (4.98 ± 2.56 vs 7.73 ± 3.06 days, p < 0.001). Patients in group C spent more days in ICU (8.80 ± 3.35 vs 5.98 ± 2.73 days, p < 0.001). The secondary infection rate was significantly higher in group C (26.7% vs 4.4%, p = 0.014). Readmission and mortality rates were comparable between the groups. Conclusion Serum procalcitonin-based algorithm in critically ill patients with sepsis could lead to a reduction in the duration of antibiotic therapy, ICU stay, and associated morbidities like secondary infection rates. It further promotes antibiotic stewardship without any adverse effects on the patient's outcome. How to cite this article Vishalashi SMG, Gupta P, Verma PK. Serum Procalcitonin as a Biomarker to Determine the Duration of Antibiotic Therapy in Adult Patients with Sepsis and Septic Shock in Intensive Care Units: A Prospective Study. Indian J Crit Care Med 2021;25(5):507-511.

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Serum Procalcitonin as a Biomarker to Determine the Duration of Antibiotic Therapy in Adult Patients with Sepsis and Septic Shock in Intensive Care Units: A Prospective Study.

Pardeep Kumar Verma

Papers

Prospective surveillance of device-associated health care-associated infection in an intensive care unit of a tertiary care hospital in New Delhi, India.

Linezolid resistant coagulase negative staphylococci (LRCoNS) with novel mutations causing blood stream infections (BSI) in India

Serum Procalcitonin as a Biomarker to Determine the Duration of Antibiotic Therapy in Adult Patients with Sepsis and Septic Shock in Intensive Care Units: A Prospective Study.