MIC Susceptibility Research Articles

Cryptic case: "It started with a pain in the ‘bum’, doctor"

Jasminsajna Mytheen Sahib, Lacey Sandra, Chakravarty Kuntal BHR University Hospitals NHS Trust, Romford, Essex, UK A 71-year-old male presented to A&E with a high fever, raised inflammatory markers and a gluteal abscess requiring incision and drainage. He had a history of prolonged treatment with immunosuppressive drugs for a pANCA positive systemic vasculitis with renal and pulmonary involvement. Previously, CMV was detected in a bronchoalveolar lavage (22,633genomic copies/ml) and blood (1996 genomic copies/ml) and he had been treated with oral valganciclovir. Incision and drainage of the gluteal abscess revealed gram positive branching rods. Two weeks later he developed cough, dyspnoea and fever. Pus from the gluteal abscess grew **********and CT imaging showed multiple lung abscesses. Although asymptomatic, a CT brain scan revealed a right parietal cerebral abscess. Empirically he was treated with intravenous co-trimoxazole and imipenem which was subsequently switched to meropenem. After six weeks of intravenous treatment, he was switched to oral co-trimoxazole and azithromycin based on MIC susceptibility testing. Six months later the patient was systemically well and repeat CT imaging revealed resolution of his lung abscesses and regression of his brain abscess. His gluteal abscess fully healed and he remains on co-trimoxazole and azithromycin maintenance therapy. ************ should be considered in the differential diagnosis of soft tissue infections in immunocompromised patients. Brain abscess can be asymptomatic and imaging of the brain should be performed when disseminated disease is suspected. Prompt diagnosis and antimicrobial treatment reduces mortality. Although there is no guidance on combinations and duration of treatment, prolonged antimicrobials therapy can improve outcomes. Diagnosis: Nocardia novia

Normalized Resistance Interpretation as a Tool for Establishing Epidemiological MIC Susceptibility Breakpoints

Normalized resistance interpretation (NRI) utilizes the fact that the wild-type population on the sensitive side is not affected by resistance development, and therefore a normalized reconstruction of the peak can be performed. The method was modified for MIC distributions by the introduction of helper variables, in-between values assigned the mean of the neighboring numbers of isolates. This method was used on Staphylo- coccus aureus and Escherichia coli MIC distributions for 27 antimicrobials each and obtained from the EUCAST (European Committee on Antimicrobial Susceptibility Testing) website (http://www.eucast.org/mic_distributions/). The number of isolates in each of the 54 distributions ranged from 40 to 124,472. NRI produced normalized distributions in all cases. Cutoff values were calculated for +2.0 and +2.5 standard deviations (SD) above the means and then rounded up to nearest regular MIC dilution step. EUCAST also show cutoff values, ECOFF values, which were used as the reference. The NRI generated +2.0 SD values showed the best agreement with 26 of 27 within ±1 dilution step and 17 exactly on the ECOFF values for Staphylococcus aureus, and 25 of 27 within ±1 dilution step and 14 right on the ECOFF values for Escherichia coli. NRI offers an objective method for the reconstruction of the wild-type population in an MIC distribution for a given bacterial species and an antimicrobial agent. This method offers a new tool in comparative susceptibility studies such as global surveillance of resistance, as well as in quality control in individual laboratories.

Salmonella enterica serovar Typhi de sensibilité diminuée à la ciprofloxacine

The use of fluoroquinolone (FQ) as first line therapy for typhoid fever should be reconsidered because of the emergence of Salmonella Typhi and Paratyphi A strains with decreased susceptibility to FQ, mainly from Asia. Relapse can occur when ciprofloxacin MIC is over 0.12 mg/l, as illustrated by our case report. Azithromycin can be used successfully for patients infected with reduced ciprofloxacin susceptibility isolates. Literature review led us to suggest a new therapeutic strategy for uncomplicated typhoid fever, the antibiotic was chosen according to nalidixic acid susceptibility and ciprofloxacin MIC of the strain. High-dose intravenous ceftriaxone (4 g per day) is always efficient in first line therapy. Depending on FQ susceptibility testing results, it is relayed by oral therapy with a FQ (ciprofloxacin 500 mg bid for 7 days) if the isolate has maintained susceptibility, or azithromycin (1 g first day and 500 mg per day, 7 days) if the isolate is resistant to nalidixic acid or has a ciprofloxacin MIC superior to 0.12 mg/l.

Rapid identification and antimicrobial susceptibility testing of Gram-positive cocci in blood cultures by direct inoculation into the BD Phoenix system

Rapid identification and antimicrobial susceptibility testing (AST) of the causative agent(s) of bloodstream infections are essential for the selection of appropriate antimicrobial therapy. To speed up the identification and AST of the causative agent, the fluid from blood culture bottles of a Bactec 9240 instrument (Becton Dickinson) containing Gram-positive cocci was mixed with saponin. After a 15-min incubation, the bacteria were harvested and transferred to the appropriate panel of a BD Phoenix automated microbiology system (Becton Dickinson) for identification and AST. With this approach (referred to as the direct method), we concordantly/correctly identified 56 (82%) of 68 monomicrobial cultures using the results obtained with the method currently used in our laboratory (current method) as comparator. Two (3%) isolates could not be identified and ten (15%) were misidentified. Complete agreement, concerning clinical susceptibility categories and MIC values, between the AST results determined with the direct method and the current method was found for 32 (55%) of 58 isolates. The E-test indicated that the direct method yielded a correct susceptibility profile for 13 of the remaining 26 blood culture isolates. Therefore, a concordant/correct susceptibility profile (with all antimicrobial agents tested) was obtained for 45 (77%) of 58 cultures. The overall error rate amounted to 1.9%, with the majority (1.3%) of errors being minor. Importantly, the results obtained with the direct method were available 12–24 h earlier than those obtained with the current method.

Multiple-Clones of Streptococcus agalactiae harbouring lnuB gene

Six S. agalactiae displaying an L-phenotype were recovered from recto-vaginal screening culture from 3 hospitals. S. agalactiae isolates showed susceptible MICs to erythromycin, MIC≤0.12mg/L, and azithromycin, MIC≤0.25mg/L, but resistant MICs to clindamycin, MIC=4mg/L, and lincomycin, MIC=64-128mg/L. Isolates were PCR positive for lnuB gene. Four clones were discriminated by ApaI-PFGE (n): A (3), B (1), C (1) and D (1). Here we describe for the first time the polyclonal emergence of S. agalactiae harboring the lnuB gene in Latin-America.

Antimicrobial Activities of Piperacillin-Tazobactam against Haemophilus influenzae Isolates, Including β-Lactamase-Negative Ampicillin-Resistant and β-Lactamase-Positive Amoxicillin- Clavulanate-Resistant Isolates, and Mutations in Their Quinolone Resistance-Determining Regions

Beta-lactamase-negative ampicillin-resistant (BLNAR) isolates of Haemophilus influenzae have been emerging in some countries, including Japan. The Clinical and Laboratory Standards Institute has only a susceptible MIC breakpoint (< or = 1 microg/ml) for piperacillin-tazobactam and a disclaimer comment that BLNAR H. influenzae should be considered resistant, which was adapted without presentation of data. In addition, fluoroquinolone-resistant H. influenzae isolates have recently been occasionally reported worldwide. To address these problems, we examined susceptibilities to beta-lactams, including piperacillin-tazobactam, and ciprofloxacin by microdilution and disk diffusion (only for piperacillin-tazobactam) methods, against a total of 400 recent H. influenzae clinical isolates, including 100 beta-lactamase-negative ampicillin-susceptible, beta-lactamase-positive ampicillin-resistant, BLNAR, and beta-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) isolates each. BLNAR and BLPACR isolates were tested by PCR using primers that amplify specific regions of the ftsI gene. We also detected mutations in quinolone resistance-determining regions (QRDRs) by direct sequencing of the PCR products of DNA fragments. Among beta-lactams, piperacillin-tazobactam exhibited potent activity against all isolates of H. influenzae, with all MICs at < or = 0.5 microg/ml (susceptible). A disk diffusion breakpoint for piperacillin-tazobactam of > or = 21 mm is proposed. We confirmed that all BLNAR and BLPACR isolates had amino acid substitutions in the ftsI gene and that the major pattern was group III-like (87.5%). One ciprofloxacin-resistant isolate (MIC, 16 microg/ml) and 31 ciprofloxacin-susceptible isolates (MICs, 0.06 to 0.5 microg/ml) had amino acid changes in their QRDRs. Piperacillin-tazobactam was the most potent beta-lactam tested against all classes of H. influenzae isolates. It is possible that fluoroquinolone-resistant H. influenzae will emerge since several clinical isolates carried mutations in their QRDRs.

Trailing end-point phenotype antibiotic-sensitive strains of Candida albicans produce different amounts of aspartyl peptidases

Candida albicans is an opportunistic fungal pathogen that causes severe systemic infections in immunosuppressed individuals. C. albicans resistance to antifungal drugs is a severe problem in patients receiving prolonged therapy. Moreover, trailing yeast growth, which is defined as a resistant MIC after 48 h of incubation with triazole antifungal agents but a susceptible MIC after 24 h, has been noted in tests of antifungal susceptibility against some C. albicans isolates. In this context, we recently noticed this phenomenon in our routine susceptibility tests with fluconazole/itraconazole and C. albicans clinical isolates. In the present study, we investigated the production of cell-associated and secreted aspartyl peptidases (Saps) in six trailing clinical isolates of C. albicans, since this class of hydrolytic enzymes is a well-known virulence factor expressed by this fungal pathogen. Sap2, which is the best-studied member of the Sap family, was detected by flow cytometry on the cell surface of yeasts and as a 43-kDa polypeptide in the culture supernatant, as demonstrated by Western blotting assay using an anti-Sap1-3 polyclonal antibody. Released aspartyl peptidase activity was measured with BSA hydrolysis and inhibited by pepstatin A, showing distinct amounts of proteolytic activity ranging from 5.7 (strain 44B) to 133.2 (strain 11) arbitrary units. Taken together, our results showed that trailing clinical isolates of C. albicans produced different amounts of both cellular and secreted aspartyl-type peptidases, suggesting that this phenotypic feature did not generate a regular pattern regarding the expression of Sap.

Comparison of 24-Hour and 48-Hour Voriconazole MICs as Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document) in Three Laboratories: Results Obtained with 2,162 Clinical Isolates of Candida spp. and Other Yeasts

We evaluated the performance of the 24-h broth microdilution voriconazole MIC by obtaining MICs for 2,162 clinical isolates of Candida spp. and other yeasts; the 24-h results were compared to 48-h reference MICs to assess essential, as well as categorical, agreement. Although the overall essential agreement was 88.6%, it ranged from 96.4 to 100% for 6 of the 11 species or groups of yeasts tested. The overall categorical agreement was 93.2%, and it was above 90% for eight species. However, unacceptable percentages of very major errors (false susceptibility) were observed for Candida albicans (2.7%), C. glabrata (4.1%), C. tropicalis (9.7%), and other less common yeast species (9.8%). Since it is essential to identify potentially resistant isolates and breakpoints are based on 48-h MICs, it appears that the 24-h MIC is not as clinically useful as the 48-h reference MIC. However, further characterization of these falsely susceptible MICs for three of the four common Candida spp. is needed to understand whether these errors are due to trailing misinterpretation or if the 48-h incubation is required to detect voriconazole resistance. Either in vivo versus in vitro correlations or the determination of resistance mechanisms should be investigated.

Twenty-five year epidemiology of invasive methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered at a burn center

Over the past two decades, an epidemiologic emergence of methicillin-resistant Staphylococcus aureus (MRSA) infections has occurred from that of primarily hospital-associated to community-associated. This emergence change has involved MRSA of different pulsed-field types (PFT), with different virulence genes and antimicrobial resistance patterns. In this study we, evaluate the changes in PFT and antimicrobial resistance epidemiology of invasive MRSA isolates over 25 years at a single burn unit. Isolates were tested by pulsed-field gel electrophoresis (PFGE), broth microdilution antimicrobial susceptibility testing, and PCR for the virulence factors Panton–Valentine leukocidin (PVL) and arginine catabolic mobile element (ACME), and the resistance marker staphylococcal chromosomal cassette mec (SCC mec). Forty isolates were screened, revealing stable vancomycin susceptibility MIC without changes over time but decreasing susceptibility to clindamycin and ciprofloxacin. The majority of PFGE types were MRSA USA800 carrying the SCC mec I element and USA100 carrying the SCC mec II element. No strains typically associated with community-associated MRSA, USA300 or USA400, were found. USA800 isolates were predominately found in the 1980s, USA600 isolates were primarily found in the 1990s, and USA100 isolates were found in the 2000s. The PVL gene was present in only one isolate, the sole USA500 isolate, from 1987. The virulence marker ACME was not detected in any of the isolates. Overall, a transition was found in hospital-associated MRSA isolates over the 25 years, but no introduction of community-associated MRSA isolates into this burn unit. Continued active surveillance and aggressive infection control strategies are recommended to prevent the spread of community-acquired MRSA to this burn unit.

Highly Susceptible Strains of Typhoid Bacilli Encountered in Jamaica

Background: Unlike reports of multidrug-resistant Salmonella enterica serovar typhi (S. typhi) in countries around the world, strains encountered in Jamaica have been uniformly susceptible to all the anti-typhoid drugs and also to other antibiotics by disc method. We have been maintaining these isolates on Dorset-egg medium over the years. In this report, we examine the MICs of 4 front-line antibiotics against 41 unduplicated isolates(one from a patient) encountered in consecutive 17 years between 1984 and 2000 at the University Hospital in Kingston, Jamaica. Methods: The MICs were determined by E test(AB Biodisk, Solna, Sweden) using E. coli ATCC 25922 as control. Manufacturers’ instructions in regard to media, inoculum density and incubation parameters were followed strictly. Our observation of extremely low MICs (see results below) made us to do the tests repeatedly and read the results independently by each of us (NCB and OH) and repeat again if we differed in reading by more than one E test dilution. Results: The MICs( g/ml) of the four antibiotics were Chloramphenicol MIC range 2—4, MIC50 3 and MIC90 3; Ampicillin MIC range 0.125—1, MIC50 0.25 and MIC90 0.5; Trimethprim/Sulpha MIC range 0.023—0.064, MIC50 0.032 and MIC90 0.047; Ceftriaxone MIC range 0.023—0.047, MIC50 0.032 and MIC90 0.047. All isolates were susceptible. MICs were extremely low, fell in a narrow range and far below the standard susceptible(CLSI) Breakpoint MICs of the antibiotics. We have not seen any report of such a highly susceptible strains of typhoid bacilli from anywhere in the world. Conclusion: Considering the growing increase of multidrug-resistant typhoid in countries around the world and reports of isolation of strains with MICs of front-line antibiotics of more than 256 g/ml(Hirose K et al Antimicrob Ag Chemother 45:956—958,2001), the highly susceptible nature of strains encountered in Jamaica is noteworthy. These unique strains which we call ‘Jamaica strains’ have been persisting in this island country throughout the years.

Correction of a Reference to Clinical Laboratory Standards Institute Interpretive Criteria

To the EditorIn the 15 February 2008 issue of Infectious Diseases, Anthony et al. [1] state, in the Methods section of their article, that the Clinical Laboratory Standards Institute interpretive criteria for Enterobacteriaceae were used for both Enterobacteriaceae and A. baumannii (susceptible MIC, ^2 /?g/mL; intermediate MIC, >2 or <8 jLtg/mL; resistant MIC, ^8 /?g/mL) (p. 567). The authors incorrectly cited the and Laboratory Standards Institute (CLSI) as the source for the interpretive criteria. There are no established CLSI interpretive criteria [2] for tigecycline, because the manufacturer has not requested that the CLSI establish and publish interpretive criteria for tigecycline in their laboratory standards.

Detecting hVISA

Rates of reduced vancomycin susceptibility (RVS) among isolates of methicillin-susceptible Staphylococcus aureus (MSSA), especially methicillin-resistant S. aureus (MRSA), have increased. Although vancomycin remains the therapeutic mainstay for MRSA, clinical response to vancomycin has been compromised by RVS among our hospital clones. Laboratories need simple procedures to detect these organisms. Whilst routine disc or MIC susceptibility testing is not reliable, some useful screening procedures are available.

Multiplex Asymmetric PCR-Based Oligonucleotide Microarray for Detection of Drug Resistance Genes Containing Single Mutations in Enterobacteriaceae

A multiplex asymmetric PCR (MAPCR)-based microarray method was developed for the detection of 10 known extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated AmpC beta-lactamase genes in gram-negative bacteria and for the typing of six important point mutations (amino acid positions 35, 43, 130, 179, 238, and 240) in the bla(SHV) gene. The MAPCR is based on a two-round reaction to promote the accumulation of the single-stranded amplicons amenable for microarray hybridization by employing multiple universal unrelated sequence-tagged primers and elevating the annealing temperature at the second round of amplification. A strategy to improve the discrimination efficiency of the microarray was constituted by introducing an artificial mismatch into some of the allele-specific oligonucleotide probes. The microarray assay correctly identified the resistance genes in both the reference strains and some 111 clinical isolates, and these results were also confirmed for some isolates by direct DNA sequence analysis. The resistance genotypes determined by the microarray correlated closely with phenotypic MIC susceptibility testing. This fast MAPCR-based microarray method should prove useful for undertaking important epidemiological studies concerning ESBLs and plasmid-mediated AmpC enzymes and could also prove invaluable as a preliminary screen to supplement phenotypic testing for clinical diagnostics.

Aluminium AA2024 T351 aeronautical alloy: Part 1. Microbial influenced corrosion analysis

The aim of this paper was to correlate the elemental distribution of alloying elements with the MIC attack morphology of the AA2024 T351 alloy by the fungus Hormoconis resinae. Anodic polarisation was applied up to the E p of the AA22024 alloy after different thermal treatments, especially T351, and to Al 99.999% as reference. The aqueous solutions were sterile Bushnell–Haas culture medium employed both as mineral nutrient for fungal growth and as support electrolyte. The variation in aggressiveness of cultures with time was also electrochemically analysed. The attack after different tests was evaluated using ESEM, SEM, EDX and optical microscopy. It was demonstrated the MIC susceptibility of the AA2024 T351 alloy to fungal cultures and the dangerous tunnelling morphology of the respective attack through grain boundaries.

Comparison of Etest, Vitek and agar dilution for susceptibility testing of colistin

In total, 172 isolates of Enterobacteriaceae, Acinetobacter spp., Pseudomonas aeruginosa and Stenotrophomonas maltophilia were tested for susceptibility to colistin by agar dilution, Etest and the Vitek 2 system. Isolates with a colistin MIC < or =2 mg/L were considered to be susceptible. Fifty-four (31%) Gram-negative isolates were resistant to colistin. Categorical agreement between agar dilution and Etest was 87%, and between agar dilution and Vitek 2 was 82%. Based on the data obtained, the Vitek 2 system was unreliable for detecting colistin resistance, and results obtained by Etest may require confirmation by a standard MIC susceptibility testing method.

P2035 In vitro activity of tigecycline and linezolid against nosocomial MRSA strains

The aim of this study was to determine the in vitro antimicrobial activity of recently licensed quinupristin/dalfopristin and linezolid which have not yet been in clinical use in Turkey against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains isolated from various clinical specimens by using the Etest. The results showed that all MRSA strains were fully susceptible to both the new compounds. All strains were inhibited by 1 mg/l quinupristin/dalfopristin (mode MIC 0.38 mg/l) and by 3 mg/l linezolid (mode MIC 1.5 mg/l). Four strains of Enterococcus faecium showed an increase of resistance of 2–3 mg/l to quinupristin/dalfopristin (susceptible mode MIC 0.38 mg/l). With linezolid, all strains except two fell within the range 0.75–2.0 mg/l.

R2261 Venous access ports. Prospective study to analyse use-related complications

Non-fermentative Gram-negative bacteria (Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia and Acinetobacter spp.) are intrinsically less susceptible to many antimicrobial agents. Two-drug combinations have been used to treat infections caused by less susceptible pathogens. In this study, the antibacterial activity of garenoxacin (GARX) with non-quinolones was examined. The non-quinolones evaluated were cefepime (CEPI), imipenem (IMIP), aztreonam (AZTR), piperacillin–tazobactam (PIPC/TZ), amikacin (AMK), ceftazidime (CTAZ), trimethoprim–sulphamethoxazole (TMP/SMX) and ticarcillin–clavulanate (TICC/CA). Synergism was determined by time-kill analysis using GARX (at 2× its MIC, not to exceed 4 mg/l) and the second drug (at 1× MIC, not to exceed its susceptible MIC breakpoint), and is defined as ≥2 log10 enhanced killing at 24 h with the combination. Partial synergy is defined as ≥1.5 log10 but <2 log10 enhanced killing with the drug combination. Synergy/partial synergy was observed most often with GARX plus: CEPI, AZTR, PIPC/TZ, IMIP (five strains each) or AMK (four strains) vs. eight P. aeruginosa; CTAZ, AZTR (five strains each) vs. six B. cepacia; TICC/CA (six strains), CEPI, CTAZ or AMK (five strains each) vs. eight S. maltophilia; and CEPI, AMK (three strains each) or CTAZ, TICC/CA (two strains each) vs. four Acinetobacter spp. In conclusion, synergistic killing was observed frequently with GARX plus a non-quinolone bactericidal agents against non-fermentative Gram-negative bacteria, including strains intermediately susceptible/resistant to one or both agents.

Effects of Phenotype and Genotype on Methods for Detection of Extended-Spectrum-β-Lactamase-Producing Clinical Isolates ofEscherichia coliandKlebsiella pneumoniaein Norway

Consecutive clinical isolates of Escherichia coli (n = 87) and Klebsiella pneumoniae (n = 25) with reduced susceptibilities to oxyimino-cephalosporins (MICs > 1 mg/liter) from 18 Norwegian laboratories during March through October 2003 were examined for bla(TEM/SHV/CTX-M) extended-spectrum-beta-lactamase (ESBL) genes, oxyimino-cephalosporin MIC profiles, ESBL phenotypes (determined by the ESBL Etest and the combined disk and double-disk synergy [DDS] methods), and susceptibility to non-beta-lactam antibiotics. Multidrug-resistant CTX-M-15-like (n = 23) and CTX-M-9-like (n = 15) ESBLs dominated among the 50 ESBL-positive E. coli isolates. SHV-5-like (n = 9) and SHV-2-like (n = 4) ESBLs were the most prevalent in 19 ESBL-positive K. pneumoniae isolates. Discrepant ESBL phenotype test results were observed for one major (CTX-M-9) and several minor (TEM-128 and SHV-2/-28) ESBL groups and in SHV-1/-11-hyperproducing isolates. Negative or borderline ESBL results were observed when low-MIC oxyimino-cephalosporin substrates were used to detect clavulanic acid (CLA) synergy. CLA synergy was detected by the ESBL Etest and the DDS method but not by the combined disk method in SHV-1/-11-hyperproducing strains. The DDS method revealed unexplained CLA synergy in combination with aztreonam and cefpirome in three E. coli strains. The relatively high proportion of ESBL-producing E. coli organisms with a low ceftazidime MIC in Norway emphasizes that cefpodoxime alone or both cefotaxime and ceftazidime should be used as substrates for ESBL detection.

Evaluation of the susceptibility of Aeromonas salmonicida to oxytetracycline and tetracycline using antimicrobial disk diffusion and dilution susceptibility tests

The development of resistance to antibiotics commonly used in animal production is an increasing concern for agriculture industries and public health. This study examined the utilisation of proposed standard methods for antimicrobial susceptibility testing as described by Alderman and Smith [Alderman, D.J., Smith, P. 2001. Development of draft protocols of standard reference methods for antimicrobial agent susceptibility testing of bacteria associated with fish diseases. Aquaculture. 196, 211–243.] for oxytetracycline (OTC) and tetracycline (TET). Fifty strains of Aeromonas salmonicida subsp. salmonicida were tested using disk diffusion and MIC techniques, with comparison of incubation periods of 24 and 48 h. The relationship between the MIC and the disk diffusion data was also used to evaluate possible breakpoints for the isolates utilised in this experiment. Susceptible and non-susceptible MIC breakpoints of ≤1 μg/ml and >16 μg/ml, and ≤1 μg/ml and >4 μg/ml fit the datasets for OTC and TET respectively. The calculation of the inhibition zone breakpoints using best-fit line equations yielded values of 15 and 26 mm for OTC and 21 and 28 mm for TET, for the non-susceptible and susceptible breakpoints respectively. The apparent differences in the inhibition zone distributions of the two tetracycline derivatives presented in this study argue for further investigation of breakpoints, with the inclusion of more bacterial strains of intermediate resistance as well as methodology development of susceptibility testing for both oxytetracycline and tetracycline.

TREATMENT OF ENTERIC FEVER IN CHILDREN ON THE BASIS OF CURRENT TRENDS OF ANTIMICROBIAL SUSCEPTIBILITY OF SALMONELLA ENTERICASEROVAR TYPHI AND PARATYPHI A

Purpose: Recent reports indicate decreased susceptibility of S. typhi to fluoroquinolones, especially ciprofloxacin. Chloramphenicol has been suggested as first line therapy of enteric fever in many studies. This is a prospective study that describes the trends of antimicrobial susceptibility of S. typhi and S. paratyphi A causing bacteraemia in children and reports therapeutic failure to ciprofloxacin and evaluates the possible use of chloramphenicol, ampicillin, ciprofloxacin and third generation cephalosporins as first line therapy in the treatment of enteric fever in children. Methods: The present study was conducted from April 2004 to March 2005 in a superspeciality children hospital at New Delhi. A total of 56 S. typhi and five S. paratyphi A isolates were obtained among the 673 blood cultures performed. Antimicrobial testing was done using disk diffusion technique (NCCLS method) for 13 antimicrobials and MICs were calculated for ampicillin, ciprofloxacin, chloramphenicol and cefotaxime. Analysis of data was done using WHONET software. Results: All 56 isolates of S. typhi were sensitive to amoxycillin+clavulanate, gentamicin, cefixime, cefotaxime and ceftazidime. Multidrug resistance (MDR, resistance to three drugs) was seen in 22 cases (39%) and resistance to five drugs was seen in 12 cases (21%). Only two isolates were resistant to chloramphenicol (3%). MIC90 for ampicillin, chloramphenicol, ciprofloxacin and cefotaxime were 1.0 μg/ml, 4.0 μg/ml, 64 μg/ml and 0.125 μg/ml respectively. All S. paratyphi A isolates were sensitive to ampicillin and chloramphenicol and resistant to nalidixic acid.MIC distribution data for chloramphenicol revealed elevated MIC but still in susceptible range. Conclusions: There is an urgent need for further clinical studies to evaluate response to chloramphenicol in such cases. Antimicrobial susceptibility data and MIC distribution favour use of ampicillin as a drug of choice for the treatment of enteric fever. Third generation cephalosporins are also useful but their use should be restricted for complicated cases.