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Year : 2014  |  Volume : 57  |  Issue : 2  |  Page : 275-277
Multidrug-resistant Staphylococcus hominis subsp. novobiosepticus causing septicemia in patients with malignancy


1 Department of Laboratory Medicine, Delhi State Cancer Institute, Dilshad Garden, New Delhi, India
2 Department of Clinical Oncology, Delhi State Cancer Institute, Dilshad Garden, New Delhi, India

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Date of Web Publication19-Jun-2014
 

   Abstract 

A new subspecies of Staphylococcus hominis described by Kloos et al. in 1998 and named S. hominis subsp. novobiosepticus (SHN) has been implicated in nosocomial outbreaks. Multidrug resistance, including resistance to novobiocin and oxacillin, is a particularly important feature of SHN. In our institute, we encountered 13 cases of S. hominis subsp. hominis in cancer patients with septicemia, of which seven were methicillin resistant. The isolates were identified by VITEK ® 2 compact automated system, using GP REF 21342 identification card and antimicrobial susceptibility testing card P-628. The biochemical reactions and antibiotic susceptibility pattern of the seven methicillin-resistant isolates were re-analyzed and patient details were re-checked to finally identify them as SHN. The increasing number of cases reporting isolation of SHN from biological specimens point to potential virulence and clinical importance of this bacterium.

Keywords: Malignancy, Staphylococcus hominis subsp. novobiosepticus, VITEK ® 2 compact

How to cite this article:
Roy P, Ahmed NH, Biswal I, Grover RK. Multidrug-resistant Staphylococcus hominis subsp. novobiosepticus causing septicemia in patients with malignancy. Indian J Pathol Microbiol 2014;57:275-7

How to cite this URL:
Roy P, Ahmed NH, Biswal I, Grover RK. Multidrug-resistant Staphylococcus hominis subsp. novobiosepticus causing septicemia in patients with malignancy. Indian J Pathol Microbiol [serial online] 2014 [cited 2022 Jan 18];57:275-7. Available from: https://www.ijpmonline.org/text.asp?2014/57/2/275/134708



   Introduction Top


Staphylococcus hominis belongs to the family Staphylococcaceae. It has two subspecies: hominis and novobiosepticus. Studies have shown that antibiotic-resistant isolates of S. hominis belong to S. hominis subsp. novobiosepticus (SHN). [1] Although S. hominis subsp. hominis is commonly isolated from human skin, there are no reports of the isolation of SHN from healthy human skin. [2] We describe cases of SHN isolated from blood samples of cancer patients with septicemia. The patients underwent thorough clinical evaluation; detailed history was taken, and physical examination along with follow-up was done. Informed consent was obtained from all the patients before every procedure.


   The cases Top


From August 01, 2013 to September 15, 2013; thirteen isolates of S. hominis were obtained from cases of blood stream infections with underlying malignancy. Seven of these isolates were resistant to methicillin (interpreted from oxacillin resistance). On closer analysis of antibiogram and biochemicals, these methicillin resistant S. hominis isolates were identified as SHN.

The first case was a 40-year-old male patient with carcinoma of lung on chemotherapy, who presented with cough, fever and breathlessness. His hematological parameters showed polymorpholeukocytosis; total leucocyte count was 13,470/ml 3 of blood, with 92% neutrophils. Blood sample was collected aseptically and processed in BacTAlert (BioMe΄rieux, Durham, North Carolina/USA). Positive signal was detected after 24 h of incubation, following which it was subcultured on blood agar and MacConkey agar. After overnight incubation at 37°C, blood agar showed non-pigmented (grey-white), opaque, entire, butyrous, non-hemolytic, slightly convex to umbonate colonies of size 1-2 mm; growth on Mac-Conkey agar was scanty. Gram stained smear from the growth revealed Gram-positive cocci, which were catalase positive and coagulase negative. The growth was then subjected to identification by the automated VITEK ® 2 compact (C) (Biomeriux, North Carolina/USA) using Gram-positive GP REF 21342 identification card. The identification was done as S. hominis subsp. hominis. The pathogenicity of this coagulase negative Staphylococcus was confirmed by promptly culturing a repeat sample from the patient. Antimicrobial susceptibility testing (AST) was done using AST card P-628. Antibiogram results were expressed as susceptible, intermediate or resistant according to the criteria of the clinical laboratory standards institute (CLSI) M100-S23 (2013). [3] The isolate was found to be resistant to oxacillin, ciprofloxacin, erythromycin and trimethoprim/sulfamethoxazole. However, it was susceptible to clindamycin, gentamicin, vancomycin, linezolid and daptomycin.

Methicillin resistant S. hominis subsp. hominis were isolated from blood samples of six more cancer patients who developed symptoms and signs of bacteremia while on chemotherapy [Table 1]. Antibiotic sensitivity profile of the isolates obtained was similar to the previously described isolate except that two of them were resistant to clindamycin too [Table 2]. All the patients were successfully treated with intravenous vancomycin.

The biochemical details showed that all the isolates were novobiocin resistant and did not produce acid aerobically from N-acetyl-D-glucosamine. Two isolates were negative for acid production from D-trehalose aerobically, while five were positive for it. All the isolates were also uniformly resistant to the first line antibiotics for Staphylococcus spp. except that five isolates were sensitive to clindamycin. S. hominis subsp. hominis, unlike SHN is novobiocin sensitive, produces acid aerobically from both N-acetyl-D-glucosamine and D-trehalose and is also sensitive to most of the antibiotics recommended by CLSI M100-S23 (2013) for Staphylococcus spp. It is a known fact that Vitek identifies coagulase-negative staphylococci (CoNS) especially S. hominis with low discrimination and further differentiation into subspecies must be based on analysis of the antibiotic susceptibility profile and biochemical reactions. [4] Therefore based on the biochemical properties and antibiotic susceptibility profile, the isolates were identified as SHN.
Table 1: Demographic characteristics and laboratory findings of patients infected with SHN

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Table 2: Antimicrobial susceptibility results of the SHN isolates

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   Discussion Top


CoNS are currently recognized as one of the most important nosocomial pathogens world-wide, principally related to bloodstream infections. [5] Staphylococcus epidermidis is the most frequent CoNS species associated with these infections, but results of surveillance studies indicate a varying frequency, depending on the geographical region. [6],[7] In addition, a substantial increase in the frequency of methicillin resistance among CoNS isolates has occurred over recent decades. Methicillin-resistant isolates and those resistant to other antimicrobials are particularly important because they have narrow therapeutic options. Glycopeptides are usually the treatment of choice for infections caused by these micro-organisms. However, due to the emergence of vancomycin-resistant enterococci and staphylococci, reduction in the use of this antimicrobial agent has been recommended. [8],[9] The accurate detection of pathogenic methicillin-resistant CoNS isolates by clinical microbiology laboratories is of crucial importance in guiding therapy and promoting the correct use of glycopeptides. [10]

Recently, isolation of novel methicillin-resistant subspecies of S. hominis, SHN, has been reported from blood and other clinical specimens. This subspecies differs from classical S. hominis, now S. hominis subsp. hominis, by the phenotypic characteristics of novobiocin resistance and the inability to ferment D-trehalose and N-acetyl-D-glucosamine. [2] The name derives from the combination of novobio-pertaining to the property of novobiocin resistance, and septicus-pertaining to the ability to cause septicemia. [10] The 16S ribosomal ribonucleic acid sequences of the two subspecies differ at 3 positions over 410 bp; the grlA sequences differ at 6 positions over 119 bp. These sequence differences define SHN and S. hominis subsp. hominis sequevars. Although the precise relationship between the S. hominis sequevars and their phenotypic subspecies remains to be determined, studies indicate that antibiotic-resistant clinical isolates of S. hominis belong almost exclusively to the SHN sequevar. [1]

All strains of SHN are resistant to novobiocin, nalidixic acid and oxacillin and are resistant or have intermediate resistance to gentamicin. Many strains are resistant to erythromycin, clindamycin, trimethoprim/sulfamethoxazole and ciprofloxacin. The combined resistance to novobiocin (and nalidixic acid) and oxacillin (and methicillin) may be intrinsic to the subspecies SHN. There are two hypotheses explaining the origin of the combined resistance, one of which suggests that the genes controlling resistance to novobiocin (nov or gyrB) and methicillin (mecA) have been introduced simultaneously by the acquisition of heterologous deoxyribonucleic acid (DNA) from a methicillin-resistant strain of one of the novobiocin-resistant species that is a member of the Staphylococcus sciuri or the Staphylococcus saprophyticus species groups. This theory is further corroborated by the fact that in various strains of Staphylococcus aureus, S. epidermidis and Staphylococcus haemolyticus, the nov (or gyrB), gyrA and mecA genes are relatively closely linked on the chromosome and occur together on one of the SmaI fragments. The second hypothesis states that insertion of the mecA gene and its flanking sequences into the chromosome of SHN might have an effect on the expression of a closely linked, resident nov gene, converting the host from novobiocin-susceptible to novobiocin-resistant. [2]

We extensively reviewed the literature for human infections caused by SHN. It appears that the subspecies SHN was formed relatively recently, based on the rather similar macrorestriction patterns of chromosomal DNA, colony morphology, plasmid profiles and antibiograms of different strains. [2] In the limited number of reported cases, we found no clear age or gender predominance. SHN infections are usually high in morbidity, but have a low rate of mortality. This new, divergent subspecies was first described by Kloos et al. in 1998 in which 26 strains of SHN were isolated from human blood cultures, a wound, a breast abscess and a catheter tip between 1989 and 1996. [2] In an article in 2001, it was found to be the cause of several invasive infections at a hospital in New Jersey. [1] In 2005, a nosocomial outbreak was found to be caused by a SHN clone in a neonatal intensive care unit in the city of Madrid, Spain. [10] SHN has been reported from blood samples of three patients with bloodstream infections admitted in the intensive care unit of a tertiary care hospital in Brazil in 2006. [11] In 2008, six isolates of SHN were reported from hospitalized patients with bloodstream infections in two Brazilian hospitals. [12]

No cases of infection caused by SHN have been yet reported from India. This pathogen might be under-reported in Indian set up where most of the laboratories where manual processing is followed do not speciate CoNS; and the automated systems like VITEK and MicroScan are not able to categorize SHN. [1],[4]


   Conclusion Top


Cancer patients are immune-compromised due to the malignancy, superadded with long duration of treatment with cytotoxic drugs and radiotherapy. Therefore, they are more prone to infections by uncommon organisms than the general population. To the best of our knowledge, this is the first instance when SHN has been found to cause infections in patients with underlying malignancy; and is the first time when this organism is being reported from India. This study highlights the growing importance of SHN as a human pathogen and advocates greater alertness to detect this organism; since unlike its commensal counterpart S. hominis subsp. hominis - it has the propensity to cause serious infections especially in immune-compromised patients.

 
   References Top

1.Fitzgibbon JE, Nahvi MD, Dubin DT, John JF. A sequence variant of Staphylococcus hominis with a high prevalence of oxacillin and fluoroquinolone resistance. Res Microbiol 2001;152:805-10.  Back to cited text no. 1
    
2.Kloos WE, George CG, Olgiate JS, Pelt LV, McKinnon ML, Zimmer BL, et al. Staphylococcus hominis subsp. novobiosepticus subsp. nov. a novel trehalose-and N-acetyl-D-glucosamine-negative, novobiocin- and multiple-antibiotic-resistant subspecies isolated from human blood cultures. Int J Systemic Bacteriol 1998;48:799-812.  Back to cited text no. 2
    
3.Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty Third Informational Supplement. CLSI document M100-S23; 2013;33:1.   Back to cited text no. 3
    
4.Spanu T, Sanguinetti M, Ciccaglione D, D'Inzeo T, Romano L, Leone F, et al. Use of the VITEK 2 system for rapid identification of clinical isolates of Staphylococci from bloodstream infections. J Clin Microbiol 2003;41:4259-63.  Back to cited text no. 4
    
5.Pfaller MA, Jones RN, Doern GV, Sader HS, Kugler KC, Beach ML. Survey of blood stream infections attributable to Gram-positive cocci: Frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY Antimicrobial Surveillance Program. SENTRY Participants Group. Diagn Microbiol Infect Dis 1999;33:283-97.  Back to cited text no. 5
    
6.Yamazumi T, Furuta I, Diekema DJ, Pfaller MA, Jones RN. Comparison of the Vitek Gram-positive susceptibility 106 card, the MRSA-Screen latex agglutination test, and mecA analysis for detecting oxacillin resistance in a geographically diverse collection of clinical isolates of coagulase-negative staphylococci. J Clin Microbiol 2001;39:3633-6.  Back to cited text no. 6
    
7.Sader HS, Gales AC, Pfaller MA, Mendes RE, Zoccoli C, Barth A, et al. Pathogen frequency and resistance patterns in Brazilian hospitals: Summary of results from three years of the SENTRY Antimicrobial Surveillance Program. Braz J Infect Dis 2001;5:200-14.  Back to cited text no. 7
    
8.Center KJ, Reboli AC, Hubler R, Rodgers GL, Long SS. Decreased vancomycin susceptibility of coagulase-negative staphylococci in a neonatal intensive care unit: Evidence of spread of Staphylococcus warneri. J Clin Microbiol 2003;41:4660-5.  Back to cited text no. 8
    
9.Van Der Zwet WC, Debets-Ossenkopp YJ, Reinders E, Kapi M, Savelkoul PH, Van Elburg RM, et al. Nosocomial spread of a Staphylococcus capitis strain with heteroresistance to vancomycin in a neonatal intensive care unit. J Clin Microbiol 2002;40:2520-5.  Back to cited text no. 9
    
10.Chaves F, García-Alvarez M, Sanz F, Alba C, Otero JR. Nosocomial spread of a Staphylococcus hominis subsp. novobiosepticus strain causing sepsis in a neonatal intensive care unit. J Clin Microbiol 2005;43:4877-9.  Back to cited text no. 10
    
11.d'Azevedo PA, Trancesi R, Sales T, Monteiro J, Gales AC, Pignatari AC. Outbreak of Staphylococcus hominis subsp. novobiosepticus bloodstream infections in São Paulo city, Brazil. J Med Microbiol 2008;57:256-7.  Back to cited text no. 11
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12.Palazzo IC, d'Azevedo PA, Secchi C, Pignatari AC, Darini AL. Staphylococcus hominis subsp. novobiosepticus strains causing nosocomial bloodstream infection in Brazil. J Antimicrob Chemother 2008;62:1222-6.  Back to cited text no. 12
    

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Correspondence Address:
Nishat Hussain Ahmed
Laboratory Medicine, Delhi State Cancer Institute, Dilshad Garden, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.134708

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