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Jan 15, 2008 - The patient had not received any treatment prior to the urine sampling. He was empirically treated with 5.2 g of intravenous.
Research letters not been reported previously in pseudomonads, it is not known what percentage of P. aeruginosa isolates are heteroresistant to the drug and what clinical impact this heteroresistance may have. Also, whether the use of piperacillin/tazobactam may gradually lead to the selection of mutant subpopulations that might subsequently compromise treatment still remains unknown. In P. aeruginosa, a heterogeneous mode of resistance to blactams has been shown to emerge readily in hypermutable strains.4 The heteroresistant phenotype of our isolate resembles persister cells rather than mutants,5 due to the fact that the heteroresistant subpopulations return to the native phenotype when re-tested and that might partially explain the successful treatment with piperacillin/tazobactam. The fact that the drug achieves high urine concentrations may also have contributed to the favourable outcome. A similar strategy of bacteria to develop persister cells under antibiotic pressure has also been observed in A. baumannii.3 Should antimicrobials against which bacteria produce persisters still remain effective, as shown for piperacillin/tazobactam in P. aeruginosa, it is important when it comes to the treatment of multidrug-resistant pseudomonal infections. Larger studies are necessary to determine the frequency of infections due to piperacillin/tazobactamheterore istant isolates and their therapeutic consequences.

No specific funding was received for this study.

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References

Figure 1. (a) Disc diffusion test for piperacillin/tazobactam at the time of isolation. (b) Population analysis utilizing piperacillin/tazobactam for strains PA7171 and ATCC 27853. (c) Time–kill kinetics for these strains: 106 cfu/ mL of the native populations obtained in the logarithmic phase of growth were inoculated into Mueller– Hinton broth containing 1 MIC for the native populations and viable cells were counted after 0, 1, 3, 6, 12 and 24 h.

The patient had not received any treatment prior to the urine sampling. He was empirically treated with 5.2 g of intravenous piperacillin/tazobactam (Tazocinw, Wyeth Pharmaceuticals) every 8 h. Due to a good clinical response, the treatment was not changed after the notification of the heteroresistance to piperacillin/tazobactam. No growth was noticed in repeated urine cultures 1 week after the end of treatment with piperacillin/tazobactam and 1 month after his hospital discharge. We have previously described heteroresistance to carbapenems in P. aeruginosa and A. baumannii.2,3 In the present study, we analyse the heterogeneous mode of growth of P. aeruginosa in piperacillin/tazobactam. As this heteroresistant phenotype has

1. Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis 2002; 34: 634–40. 2. Pournaras S, Ikonomidis A, Markogiannakis A et al. Characterization of clinical isolates of Pseudomonas aeruginosa heterogeneously resistant to carbapenems. J Med Microbiol 2007; 56: 66–70. 3. Pournaras S, Ikonomidis A, Markogiannakis A et al. Heteroresistance to carbapenems in Acinetobacter baumannii. J Antimicrob Chemother 2005; 55: 1055–6. 4. Macia MD, Borrell N, Perez JL et al. Detection and susceptibility testing of hypermutable Pseudomonas aeruginosa strains with the Etest and disk diffusion. Antimicrob Agents Chemother 2004; 48: 2665–72. 5. Balaban NQ, Merrin J, Chait R et al. Bacterial persistence as a phenotypic switch. Science 2004; 305: 1622–5.

Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkm519 Advance Access publication 15 January 2008

High isolation rate of Staphylococcus aureus from surgical site infections in an Indian hospital Hayath Kownhar1, Esaki Muthu Shankar1,2*, Ramachandran Vignesh2, Ramalingam Sekar1,2, Vijayakumar Velu1 and Usha Anand Rao1

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Funding

Research letters 1

Bacteriology Laboratory, Department of Microbiology, Faculty of Medicine, Dr ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India; 2YRG Centre for AIDS Research and Education, VHS Hospital Campus, Taramani, Chennai 600 113, India Keywords: surgical infections, antimicrobial susceptibility, S. aureus *Corresponding author. Tel: þ91-44-22542929; Fax: þ91-4422542939; E-mail: [email protected]

Table 1. Susceptibility of the Gram-negative and -positive bacterial isolates from SSIsa Gram-negative isolates (n ¼ 36)

Antibiotics Amikacin Ampicillin Ceftazidime Cefalexin Cefazolin Ciprofloxacin Co-trimoxazole Gentamicin

P. aeruginosa (n ¼ 23)

K. pneumoniae (n ¼ 5)

Proteus spp. (n ¼ 3)

E. coli (n ¼ 3)

C. freundii (n ¼ 1)

E. tarda (n ¼ 1)

15 (65.2) 3 (13) 18 (78.3) 14 (60.9) 14 (60.9) 21 (91.3) 5 (21.7) 6 (26.1)

4 (80) 2 (40) 3 (60) 2 (40) 2 (40) 5 (100) 1 (20) 2 (40)

3 (100) 2 (66.6) 3 (100) 2 (66.6) 3 (100) 3 (100) 1 (33.3) 1 (33.3)

1 (33.3) 1 (33.3) 3 (100) 0 0 3 (100) 1 (33.3) 3 (100)

1 (100) 0 1 (100) 0 1 (100) 1 (100) 0 1 (100)

1 (100) 1 (100) 1 (100) 1 (100) 0 1 (100) 0 1 (100)

Gram-positive isolates (n ¼ 26) Antibiotics

S. aureus (n ¼ 23)

E. faecalis (n ¼ 1)

Acinetobacter spp. (n ¼ 2)

Amikacin Ampicillin Cefalexin Ciprofloxacin Erythromycin Gentamicin Methicillin Penicillin G Vancomycin

10 (43.5) 6 (26.1) 5 (21.7) 12 (52.2) 7 (30.4) 7 (30.4) 6 (26.1) 7 (30.4) 23 (100)

1 (100) 0 0 1 (100) NT 0 NT 1 (100) 1 (100)

2 (100) 1 (50) NT 2 (100) 0 2 (100) NT 1 (50) NT

a n refers to the number of isolates tested. Results shown in the table are the numbers of susceptible isolates with percentages of isolates given in parentheses. NT refers to susceptibility not tested.

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Sir, Surgical site infection (SSI) is a major source of morbidity and mortality and is an important outcome indicator after surgery.1 SSIs are the second most frequent nosocomial infection in the general hospital population.1 A study showed that subjects who develop SSI were five times more likely to be re-admitted and re-operated on than those without infection and were also reported to be twice as likely to die during the post-operative period.1 Few studies of the incidence and causes of SSI and its prevention have been conducted in resource-limited countries. Furthermore, isolation and antibiogram profiles require periodical monitoring, especially in settings like India, where SSIs account for considerable morbidity and mortality rates. We evaluated the aetiological agents of SSI and their resistance patterns

at a city government hospital in Chennai, southern India during a 6 month period from January to June 2003. Ethic committee approval was obtained from the University of Madras for conducting the study. Subjects were classified as having an SSI when there was a skin eruption or purulent drainage at the surgical-site incision, positive for bacteria by culture of material obtained by aseptic means within 60 days of a surgical procedure and inflammatory signs such as pain, tenderness, localized swelling, redness and/or heat. As per the criteria, a total of 52 wound specimens of post-SSIs were analysed. Culture materials collected by washing the wound with sterile saline and applying sterile cotton swabs (Himedia, Mumbai, India) were transported on Cary & Blair media in a 08 mini cooler (Tarson, Mumbai, India), cultured and identified using standard bacteriological procedures.2 Antibiotic susceptibility testing was performed using the conventional Kirby – Bauer disc diffusion test (CLSI, formerly NCCLS).3 Sixty-two bacterial isolates were obtained on 52 cultures and 6 were declared bacteriologically sterile. Single isolates were seen in 31 (59.6%) and multiple isolates in 15 (28.8%) instances. Gram-negative bacteria predominated with (n ¼ 36) 58%, followed by (n ¼ 26) 41.9% Gram-positive isolates. The most common bacteria were Staphylococcus aureus (n ¼ 23; 37%) and Pseudomonas aeruginosa (n ¼ 23; 37%), followed by Klebsiella pneumoniae (n ¼ 5; 8%), Acinetobacter spp. (n ¼ 2; 3.2%), Proteus spp. (n ¼ 3; 4.8%), Escherichia coli (n ¼ 2; 4.8%), Citrobacter freundii (n ¼ 1; 1.6%), Edwardsiella tarda (n ¼ 1; 1.6%) and

Research letters need to be targeted to control pre-operative nasal carriage of S. aureus to avoid the risk of MRSA in surgical wounds, which could possibly influence the outcome of SSIs. In addition, repeated prevalence surveys are useful for monitoring trends in rates of SSIs and effectiveness of intervention strategies.

Funding No funding received.

Transparency declarations None to declare.

References 1. Kirkland KB, Briggs JP, Trivette SL et al. The impact of surgical-site infections in the 1990s: attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol 1999; 20: 725–30. 2. Valentina G, Lalitha MK. Isolation and identification of bacteria from pus (including drainage tube, catheter, ear, eye and genital swabs). In: Myer’s and Koshi’s Manual of Diagnostic Procedures in Medical Microbiology and Immunology/ Serology. Vellore, India: Christian Medical College and Hospital, 2001; 38 –49. 3. National Committee for Clinical Laboratory Standards. Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data: Approved Guideline M39-A. NCCLS, Wayne, PA, USA, 2002. 4. Takeyama K, Matsukawa M, Kunishima Y et al. Incidence of and risk factors for surgical site infection in patients with radical cystectomy with urinary diversion. J Infect Chemother 2005; 11: 177–81. 5. Mohanty S, Kapil A, Dhawan B et al. Bacteriological and antimicrobial susceptibility profile of soft tissue infections from Northern India. Indian J Med Sci 2004; 58: 10 –5. 6. Solomkin JS, Bjornson HS, Cainzos M et al. A consensus statement on empiric therapy for suspected Gram-positive infections in surgical patients. Am J Surg 2004; 187: 134–45.

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Enterococcus faecalis (n ¼ 1; 1.6%). The antibiogram pattern of the isolates tested is shown in Table 1. One of the most prevalent bacteria was S. aureus (37%) that comprised five (21.7%) methicillin-resistant S. aureus (MRSA). MRSA infections are of great concern due to their higher morbidity and mortality rates.4 – 6 Fortunately, all of the MRSA isolates in our study were susceptible to vancomycin (30 mg/disc). The other major concern in SSIs is S. aureus that is believed to originate from the patient’s own anterior nares. Randomized trials advocate the use of topical intranasal mupirocin ointment to effectively eradicate Staphylococcus species and more importantly S. aureus from the anterior nares soon after treatment. Furthermore, complete eradication is believed to be achieved with as little as one dose. The increased isolation rates of S. aureus stress the need to screen and treat subjects for pre-operative nasal carriage of the pathogen using topical mupirocin, which could possibly influence the aetiology of SSIs. In a study that enrolled 104 subjects with SSIs, S. aureus was predominant with 38% MRSA,4 which concurs with our findings. Another Indian study has reported the preponderance of S. aureus (with 38.56% MRSA) followed by E. coli and Pseudomonas spp. from surgical wounds. The study suggests that the absence of SSI could be an important part of the successful outcome of any operative procedure. Strict measures to reduce the detection of colonizing bacteria from the infection sites need to be ensured, and therefore culture material needs to be collected always from the deeper part of the superficial incision site, washed prior to collection with sterile saline. We suggest that the maintenance of S. aureus control strategies should be the need of the hour in Indian settings. The high prevalence of P. aeruginosa in our study may be due to the fact that it can survive well in moist environments, often causing severe tissue damage due to its invasiveness. Our results seem to be helpful in providing useful guidelines for choosing effective therapy against bacterial pathogens in SSI wounds. In addition, in high infection rate units, the periodic monitoring of microbial species and of their respective susceptibility to antibiotics is crucial. We conclude that more attempts