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Ofloxacin minimum inhibitory concentration versus disk diffusion zone diameter for Salmonella enterica serovar Typhi isolates: problems in the detection of ofloxacin resistance.

Using the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS), a total of 421 blood culture isolates of Salmonella enterica serovar Typhi obtained during 1991-2001 were tested for susceptibility to ofloxacin (OFX) by the disc diffusion method, and for the determination of minimum inhibitory concentration (MIC) values of OFX by the agar dilution method. Among 421 isolates, 248 were fully OFX-sensitive showing MICs of 0.0125-0.075 microg/ml and inhibitory zone diameters of > or =24 mm. The remaining 173 isolates (MICs of 0.5-1.5 microg/ml) that were treated with OFX did not respond to the therapy. However, 169 (97.69%) of the 173 isolates were determined to be susceptible (zone diameter > or =16 mm) by the disc diffusion method, whereas only 3 were intermediately susceptible (zone diameter 13-15 mm) and the final isolate showed OFX-resistance (zone diameter 12 mm). Thus, following the NCCLS guidelines, OFX-resistance in S. enterica serovar Typhi was not detected by the disc diffusion test. The present data suggest a revision of the NCCLS breakpoints in selecting OFX as the preferred treatment regimen for S. enterica serovar Typhi

Anti-Infective Agents↗

An evaluation of the necessity of 24-hour incubation for oxacillin minimum inhibitory concentrations.

Current standards of the National Committee for Clinical Laboratory Standards (NCCLS) for microtube dilution recommend 24-hour incubation of staphylococci when testing for oxacillin/methicillin resistance. This study was conducted to quantify the need for this requirement. Standard 16-hour readings were compared with subsequent 24-hour readings of 515 fresh clinical isolates (256 Staphylococcus aureus, 259 coagulase-negative staphylococci) that were susceptible to oxacillin (microtube dilution minimum inhibitory concentration [MIC] < or equal to 2 micrograms/mL) after 16 hours. Five hundred two of the susceptible isolates (97.5%) were still susceptible at 24 hours. The remaining 13 isolates were resistant (MIC > 2 micrograms/mL) at 24 hours. Duplicate retesting, alternative method testing (Kirby-Bauer, E-Test) and mec A gene analysis were performed on these 13 isolates. All 13 isolates possessed the mec A gene. Four isolates always tested resistant (including all 16-hour repeat microtube dilution readings), and one isolate always tested susceptible. The remaining eight isolates produced variable results suggestive of an MIC very close to the resistance/susceptible break point. Overall , conversion from susceptible to resistant was entirely dependent upon the 16-hour MIC. There were 53 isolates with 16-hour MICS of 2 micrograms/mL. All 13 converters came from this group. No isolate with an oxacillin MIC < 2 micrograms/mL at 16 hours was resistant at 24 hours. Based on these results, the authors instituted a selective reincubation of only those staphylococcal isolates with oxacillin readings of 2 micrograms/mL at 16 hours.

Coagulase↗

Comparison of fluconazole minimum inhibitory concentrations in three different formulations of RPMI-1640.

This study aimed to compare the susceptibilities of fluconazole, obtained in two laboratories, using three RPMI-1640 formulations (manufacturers') and inhibition standards (80%). A total of 39 selected Candida species (in vitro susceptible and resistant) and Cryptococcus neoformans isolates were tested in each medium by broth macro- and microdilution procedures following the National Committee for Clinical Laboratory Standards proposed reference method (M27-P). Macrodilution minimum inhibitory concentrations (MIC80%) were the lowest drug concentrations with turbidity (growth) less than or equal to that of the specific 80% inhibition standards (1:5 growth control). Microdilution MIC-2 were the lowest drug concentrations in which there was prominent decrease in growth. In general, the three formulations of RPMI-1640 medium provided similar MICs for most of the yeasts tested in both laboratories and by each test.

Candida↗

Global genomic and antimicrobial resistance profiling of Neisseria gonorrhoeae: Insights from whole genome sequencing and minimum inhibitory concentration analysis.

BACKGROUND: The rising antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a major global health concern that limits treatment options and complicates disease management. Efflux pump systems and resistance genes are key to bacteria's ability to evade antibiotics. This study examined the genetic and phenotypic resistance landscape using a large dataset of whole-genome sequences to identify key resistance mechanisms, assess efflux pump gene prevalence, and analyze regional variations in Minimum Inhibitory Concentration (MIC) values to inform treatment strategies and public health interventions. METHODS: A total of 38,585 whole-genome sequences of N. gonorrhoeae were analyzed to identify AMR determinants. This study focused on the presence and distribution of efflux pump genes (mtrC, farB, norM, and mtrA) and specific resistance genes, including tet(C) (tetracycline resistance) and aph(3')-Ia (aminoglycoside resistance). The MIC values were assessed for multiple antibiotics to evaluate resistance trends and regional variations, including penicillin, spectinomycin, zoliflodacin, gentamicin, and fluoroquinolones. RESULTS: This analysis revealed widespread resistance to multiple antibiotics. Efflux pump genes (mtrC, farB, norM, and mtrA) were found in nearly all isolates, highlighting their essential roles in resistance and adaptation. The presence of tet(C) and aph (3')-Ia varied across different Gene Presence Patterns, suggesting that regional or therapeutic factors may influence tetracycline and aminoglycoside resistance. High MIC values for penicillin were observed, likely because of blaTEM, a beta-lactamase gene responsible for beta-lactam resistance. Resistance to spectinomycin is also widespread, raising concerns about the diminishing efficacy of this antibiotic. In contrast, zoliflodacin, gentamicin, and fluoroquinolones exhibited relatively low MIC values, indicating their sustained effectiveness against N. gonorrhoeae. DISCUSSION: Efflux pump systems are key to N. gonorrhoeae resistance and adaptability. Regional MIC variations indicate that local antibiotic use shapes resistance patterns. The high resistance to penicillin and spectinomycin highlights the need for alternative treatments, whereas zoliflodacin and fluoroquinolones remain effective but require monitoring. This study emphasizes global AMR surveillance, novel therapies, and targeted antimicrobial stewardship to address multidrug-resistant infections.

Neisseria gonorrhoeae↗

Induction of pro-inflammatory cytokine release by human macrophages during exposure of Streptococcus pneumoniae to penicillin is influenced by minimum inhibitory concentration ratio.

beta-Lactam antibiotics cause release of pro-inflammatory bacterial cell wall structures. We determined the effect of penicillin treatment of Streptococcus pneumoniae on the induction of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) genes by human macrophages and the influence of antibiotic concentration and bacterial growth phase upon this induction. Gene expression was measured by real-time polymerase chain reaction (PCR) and protein was measured by enzyme-linked immunosorbent assay (ELISA). Treatment of lag phase S. pneumoniae with one-eighth minimum inhibitory concentration (MIC) penicillin resulted in enhanced expression of TNF-alpha messenger RNA (mRNA), but not TNF-alpha protein at 6h compared with untreated bacteria. IL-1beta mRNA and protein were not affected by these bacteria. MIC treatment of lag or early log phase bacteria induced both protein and mRNA for IL-1beta. Bacteria exposed to concentrations of penicillin that cause lysis (MIC) or no lysis with morphological changes (sub-MIC) induce differential patterns of pro-inflammatory cytokine expression by human macrophages.

Anti-Bacterial Agents↗

Microbiological features of vancomycin in the 21st century: minimum inhibitory concentration creep, bactericidal/static activity, and applied breakpoints to predict clinical outcomes or detect resistant strains.

The results of vancomycin susceptibility tests document that the drug continues to have activity against a wide variety of gram-positive pathogens. The subsequent emergence of vancomycin-resistant enterococci, the persistent failure of vancomycin therapy against strains tested as susceptible, and the more recent discoveries of vancomycin-intermediate or -resistant Staphylococcus aureus strains have compromised the use of vancomycin. Although analyses of surveillance studies fail to demonstrate "minimum inhibitory concentration creep" among populations of wild-type enterococci, streptococci, or staphylococci, enterococci with acquired resistance to vancomycin continue to evolve. The dominantly used automated commercial tests poorly recognize vancomycin-intermediate S. aureus, heteroresistant vancomycin-intermediate S. aureus, and vancomycin-resistant S. aureus isolates, which necessitates the use of expensive supplemental screening tests. Monitoring for appropriate serum levels of vancomycin and determinations of the bactericidal activity of vancomycin appear to best predict clinical outcome, thus creating additional diagnostic burdens for clinical laboratories. Improvements in current test methods with breakpoint criteria and expanded use of the vancomycin bactericidal assays to detect "tolerant" strains will be required to increase the value of vancomycin treatment or to refocus therapy toward the use of newer, alternative agents.

Anti-Bacterial Agents↗

Resistance pattern and assessment of phenicol agents' minimum inhibitory concentration in multiple drug resistant Chryseobacterium isolates from fish and aquatic habitats.

AIMS: To assess the susceptibility of Chryseobacterium isolates of fish and aquatic habitats to antimicrobial compounds. Special attention was paid to the resistance to chloramphenicol and florfenicol, a phenicol derivative recently licensed for use in veterinary medicine and fish farming. METHODS AND RESULTS: Sixty-seven Chryseobacterium spp. isolates and reference strains, originating mainly from different aquatic habitats, were tested using the disk-diffusion method. In addition, agar dilution was used for assessing minimum inhibitory concentration of chloramphenicol and florfenicol. In spite of (i) conditions that hampered properly standardized experiments and (ii) the heterogeneity of the isolates resulting in some aberrant values in diffusion, correlation between the two methods was confirmed. Most of the isolates exhibited considerable multiresistance to most antimicrobial drug families, and many were clearly resistant to phenicols. Molecular investigations conducted on 10 strains selected for high resistance to florfenicol did not establish the existence of floR or cmlA genes currently reported in the literature as responsible for florfenicol resistance. Nevertheless, when an efflux pump inhibitor, phenyl-arginin-beta-naphthylamide, was combined with diffusion tests, drug susceptibility to florfenicol was restored, suggesting that Chryseobacterium's resistance to this molecule is under the control of efflux mechanisms. CONCLUSIONS: Constitutive multiresistance to antibiotics is common in chryseobacteria isolated from the aquatic environment. Although no gene related to the floR family could be detected, efflux mechanisms could partly support the resistance to phenicols. SIGNIFICANCE AND IMPACT OF THE STUDY: These results explain the difficulty of treatment and clearly reflect the properties previously reported in Chryseobacterium isolates of human origin. Because several species have been involved in opportunistic infections in humans, the possible role of aquatic organisms as a source of infection should be considered.

Animals↗

Penicillin minimum inhibitory concentration drift in identical sequential Streptococcus pneumoniae isolates from colonized healthy infants.

We monitored the timing of acquisition of nasopharyngeal colonization of Streptococcus pneumoniae in 125 healthy infants during their first 2 years of life. S. pneumoniae was isolated at least once from 59 (47%) of 125 infants aged between 2 and 18 months. Twenty-four infants (19%) were colonized with penicillin-resistant S. pneumoniae at some time during the study. During the course of this investigation, we identified sequential pneumococcal isolates of the same serotype from 5 infants, in which the penicillin minimum inhibitory concentration (MIC) increased over time. For 4 of the 5 infants, sequential isolates were identical, as determined by pulsed-field gel electrophoresis. Sequential S. pneumoniae nasopharyngeal isolates from some healthy infants demonstrated drift in penicillin MIC values over time, from penicillin-susceptible to penicillin-resistant.

Child, Preschool↗

Standardization of a broth microdilution susceptibility testing method to determine minimum inhibitory concentrations of aquatic bacteria.

A multiple laboratory study was conducted in accordance with the standards established by the Clinical and Laboratory Standards Institute (CLSI), formerly the National Committee for Clinical Laboratory Standards (NCCLS), for the development of quality control (QC) ranges using dilution antimicrobial susceptibility testing methods for bacterial isolates from aquatic animal species. QC ranges were established for Escherichia coli ATCC 25922 and Aeromonas salmonicida subsp. salmonicida ATCC 33658 when testing at 22, 28 and 35 degrees C (E. coli only) for 10 different antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, flumequine, gentamicin, ormetoprim/sulfadimethoxine, oxolinic acid, oxytetracycline and trimethoprim/sulfamethoxazole). Minimum inhibitory concentration (MIC) QC ranges were determined using dry- and frozen-form 96-well plates and cation-adjusted Mueller-Hinton broth. These QC ranges were accepted by the CLSI/NCCLS Subcommittee on Veterinary Antimicrobial Susceptibility Testing in January 2004. This broth microdilution testing method represents the first standardized method for determining MICs of bacterial isolates whose preferred growth temperatures are below 35 degrees C. Methods and QC ranges defined in this study will enable aquatic animal disease researchers to reliably compare quantitative susceptibility testing data between laboratories, and will be used to ensure both precision and inter-laboratory harmonization.

Aeromonas salmonicida↗

Single and double drug susceptibility testing of Mycobacterium avium complex and mycobacteria other than the tubercle (MOTT) bacilli by a micro-dilution broth minimum inhibitory concentration (MIC) method.

SETTING: The incidence of Mycobacterioses is increasing annually, especially in patients with AIDS. There is no clear correlation between in vitro drug susceptibility testing of mycobacteria other than the tubercle (MOTT) bacilli and the in vivo response. Although in vitro, MOTT bacilli appear resistant, some patients respond to treatment possibly as a result of a synergistic action between the drugs being used. OBJECTIVE: To produce a simple method to determine which individual drugs or combinations of drugs will be effective in killing the causative organism. DESIGN: A broth microdilution method, using microtitre plates, was used to determine the minimum inhibitory concentration (MIC) of the drugs alone and then in combination. RESULTS: It was found that the MIC values of the test drugs varied between but were constant within each of the species. Mycobacterium xenopi, M. malmoense and M. kansasii showed a large amount of susceptibility while M. avium complex, M. fortuitum and M. chelonae were limited in their response. These results were reproducible. The test was also easy to perform. The drug combination studies showed that each strain of the M. avium complex tested exhibited synergy between different combinations of drugs. CONCLUSION: This method, therefore, can be used to indicate individual or combinations of drugs that will or will not act upon the Mycobacterium species isolated. The method was also very rapid, giving a result within 7 days.

Antibiotics, Antitubercular↗

Antimicrobial resistance and minimum inhibitory concentrations of bacteria isolated from bustards in the United Arab Emirates.

The resistance to 11 antimicrobial agents of bacteria isolated from clinical and postmortem cases of five species of bustards maintained in captivity in the United Arab Emirates (UAE) from 1995 to 1997 was determined by disc sensitivity. Of 226 isolates, 169 (74.8%) were gram-negative bacilli, with the majority identified as Escherichia coli (28.8%) and Pseudomonas aeruginosa (19%). The isolates of E. coli showed a high prevalence of resistance to amoxycillin (69%), tetracycline (66.7%), and sulphamethoxazole (43.3%). Moderate resistance to enrofloxacin was observed in E. coli (30%) and P. aeruginosa (19%) isolates. The minimum inhibitory concentrations (MICs) to seven antimicrobial agents were determined for 133 bacterial isolates from bustards during 1996 to 1997. Enrofloxacin (concentration required to inhibit 50% of the isolates [MIC50] < 0.5 microgram/ml) and gentamicin (MIC50 < or = 1.0 microgram/ml) exhibited good activity against both gram-negative bacilli and staphylococci isolated from bustards. Enrofloxacin (MIC50 < or = 1.5 micrograms/ml), gentamicin (MIC50 < or = 2.0 micrograms/ml), and piperacillin (MIC50 < or = 4.0 micrograms/ml) exhibited good activity against P. aeruginosa isolates. Amoxycillin/clavulanic acid showed good activity (concentration required to inhibit 90% of the isolates [MIC90] < or = 2.0 micrograms/ml) against gram-positive cocci and moderate activity (MIC50 < or = 3.0 micrograms/ml) against E. coli, Salmonella spp., and Klebsiella spp. Amoxycillin exhibited good activity (MIC50 < or = 0.5 microgram/ml) against gram-positive organisms and moderate activity (MIC50 < or = 1.0 microgram/ml) against Salmonella spp. These results provide information on the prevalence of resistant bacterial strains and the MICs of organisms derived from bustards in the UAE.

Amoxicillin↗

A comparison of the minimum inhibitory concentrations of sisomicin and of fourteen other antibiotics.

The activities of sisomicin and of fourteen other antibiotics have been compared for their inhibitory activity on all the different strains of bacteria isolated from a 3,000 bed hospital. The antibiotic sensitivity tests were performed in liquid medium and expressed as minimum inhibitory concentrations. The tests were performed over a period of four months. The results are discussed.

Anti-Bacterial Agents↗

Influence of an extended incubation period on values of minimum inhibitory concentrations of antibiotics in Stenotrophomonas maltophilia clinical strains.

In 106 Stenotrophomonas maltophilia clinical strains the susceptibility to 19 kinds of antibiotics was tested by the broth dilution micromethod at 24 h and 48 h incubation. Isolated strains demonstrated the lowest frequency of resistance to cotrimoxazole (7.5% of resistant strains at 24 h incubation and 18.9% at 48 h), ofloxacin (13.2% and 30.2%), ciprofloxacin (19.8% and 50.9%) and to cefoperazone/sulbactam (20.8% and 37.7%). The smallest growth of the number of resistant strains after extended incubation was recorded in gentamicin (by 10.4%), ceftazidime (by 11.3%) and cotrimoxazole (by 11.4%). On the contrary, the largest growth of resistance was demonstrated in cefoperazone and ciprofloxacin (by 31.1%). Average values of the growth of minimum inhibitory concentrations (MICs) were lowest in ciprofloxacin and ofloxacin (2.3 times) and highest in piperacillin/tazobactam (4.5 times) and piperacillin (5.0 times). As far as the stability of MIC is concerned, the largest occurrence of strains with the MIC growth doubled as a maximum was found in ceftazidime (78.4%), ofloxacin (76.1%) and ciprofloxacin (75.3%), the smallest in piperacillin/tazobactam (43.2%) and piperacillin (38.9%). The importance of incubation extended to 48 h during the testing of S. maltophilia strains was noted for correctly setting their susceptibility to antibiotics.

Anti-Bacterial Agents↗

Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia.

Our objective was to prospectively determine the factors influencing the probability of a good microbiological or clinical outcome in patients with nosocomial pneumonia treated with a fluoroquinolone. Levofloxacin was administered as an infusion of 500 mg/h for 1.5 h (total dose, 750 mg). For patients with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus, a second drug was added (ceftazidime or piperacillin/tazobactam for P. aeruginosa and vancomycin for methicillin-resistant S. aureus). Population pharmacokinetic studies of 58 patients demonstrated that this population handled the drug differently from populations of volunteers. Multivariate logistic regression analysis (n=47 patients) demonstrated that only the age of the patient and the achievement of an area under the curve: minimum inhibitory concentration ratio of > or =87 had a significant effect on eradication of the pathogen (P<.001). Achieving the breakpoint made the patient 4 times more likely to achieve eradication. The effect was greatest in patients > or =67 years old.

Adult↗

Minimum inhibitory concentration of various single agents and the effect of their combinations against Helicobacter pylori, as estimated by a fast and simple in vitro assay method.

OBJECTIVES: Fast and simple in vitro methods of accurately assaying anti-Helicobacter pylori (H. pylori) activity are needed to facilitate the selection of optimal drugs for the eradication of H. pylori. With that purpose in mind, we developed a broth microdilution technique that uses a 96-well flat-bottom microplate. METHODS: Clinical isolates of H. pylori were placed in 25-cm2 tissue culture flasks and were grown in an atmosphere of 5% CO2 in air at 37 degrees C and 100% humidity. Then they were inoculated in 96-well flat-bottom microplates. After 24 h, the bacterial growth was assessed by automatic measurement at A450 with a microplate reader. Minimum inhibitory concentrations (MICs) of 11 drugs against H. pylori and the effect of two-drug combinations were respectively evaluated by the broth microdilution technique and by calculating the fractional inhibitory concentration index according to the checkerboard titration method. RESULTS: The MICs of all drugs tested with this system roughly agreed with those of previous reports in which the agar dilution method was used. The MIC of lansoprazole, a proton pump inhibitor, was low (0.88 microg/ml) and surpassed that of metronidazole (3.15 microg/ml). The effect of the combination of macrolide antibiotics with tetracycline was favorable. The proton pump inhibitor demonstrated a strong additive effect with macrolide antibiotics and fostered the activity of ecabet sodium (mucosal protective agent). CONCLUSION: This system could estimate the MIC of individual drugs quickly and simply, and could accurately measure the efficacy of two-drug combinations in vitro.

Anti-Bacterial Agents↗

Evaluation of minimum inhibitory concentration of quinolones and third generation cephalosporins to Salmonella typhi isolates.

A total of 323 Salmonella typhi isolates (261 isolates obtained during 1995-99 from Ludhiana and 62 randomly selected isolates obtained between 1980-99 from Chandigarh) were analyzed for drug resistant pattern. S. typhi isolates prior to 1986 were sensitive to all the antimicrobials tested by disc diffusion method. Most common multidrug resistance pattern noticed was ACCo T i.e. resistance to ampicillin, Chloramphenicol, cotrimoxazole and tetracycline. This study has revealed that withdrawal of chloramphenicol due to high level of resistance during 1990-94, has led to re-emergence of 43-93 percent chloramphenicol sensitive mutants during 1995-99. Two S. typhi isolates in 1995 and one in 1999 from Ludhiana depicted resistance to ciprofloxacin. Susceptibility of S. typhi isolates to third generation cephalosporins ranged between 87 to 100 per cent. There was a gradual increase with time period in mean minimum inhibitory concentration (MIC) of ciprofloxacin as it increased from 0.066 ug/ml for 1980-83 S. typhi isolates to 0.13 ug/ml for the 1996-99 isolates. Similarly, cefotaxime mean MIC for 1980-83 isolate was 0.172 ug/ml which further increased up to 0.32 ug/ml for S. typhi isolates encountered between 1996-99. In contrast, mean MIC value of 0.62 ug/ml of Ceftriaxone remained unchanged irrespective of the year of isolation of S. typhi isolates.

Anti-Bacterial Agents↗

Reduced minimum inhibitory concentration of chloramphenicol for Salmonella enterica serovar typhi.

BACKGROUND: Ciprofloxacin replaced chloramphenicol (C), the best choice of antibiotic in the treatment of enteric fever, when C-resistant enteric fever emerged and caused outbreaks in different parts of the world. C-sensitive S. enterica serovar Typhi emerged again due to withdrawal of the antibiotic pressure. AIMS: To assess the in vitro efficacy of C against Salmonella enterica serovar Typhi isolates (1991-2003). MATERIAL AND METHODS: A total of 464 blood culture isolates of S. enterica serovar Typhi were subjected to C susceptibility by disc diffusion and agar dilution methods using Mueller-Hinton agar. The antibiotic susceptibility of S. enterica serovar Typhi isolates obtained in the year 2002 and 2003 was determined using ampicillin, cotrimoxazole, ciprofloxacin, nalidixic acid, ceftriaxone and cefotaxime, in addition to C. Escherichia coli strain ATCC 25922 was used as the control. Changes in C sensitivity of the isolates were analyzed using chi2 test with Yates correction. RESULTS AND CONCLUSIONS: All the isolates of 1991 were C-resistant with minimum inhibitory concentration values (MICs) of 2000-5000 mg/ml. In the following years decrease in frequency of C resistance was noticed: 1992 (50%), 1993 (32%), 1994 (27%) and 1995 (05%). The isolates of 1996-99 and 2001 were 100% C-sensitive. In 2000, sensitivity was also high (79%). The strains isolated in the year 2002 and 2003, showing reduced susceptibility of ciprofloxacin, were nalidixic acid resistant, but sensitive to the third-generation cephalosporins (ceftriaxone and cefotaxime). The MICs for C-sensitive isolates (1991-2003) ranged 0.1-5 mg/ml. Results suggest the necessity for re-evaluation of C therapy in typhoid fever.

Anti-Bacterial Agents↗

Minimum inhibitory concentration breakpoints and disk diffusion inhibitory zone interpretive criteria for tilmicosin susceptibility testing against Pasteurella multocida and Actinobacillus pleuropneumoniae associated with porcine respiratory disease.

Tilmicosin is a novel macrolide antibiotic developed for exclusive use in veterinary medicine. Tilmicosin has been approved as a feed premix to control porcine respiratory disease associated with Pasteurella multocida and Actinobacillus pleuropneumoniae. The development of antimicrobial susceptibility testing guidelines for tilmicosin was predicated on the relationship of clinical efficacy studies that demonstrated a favorable therapeutic outcome, on pharmacokinetic data, and on in vitro test data, as recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The approved breakpoints for the minimum inhibitory concentration dilution testing for both species are resistant, > or = 32 microg/ml, and susceptible, < or = 16 microg/ml. The zone of inhibition interpretive criteria for disk diffusion testing with a 15-microg tilmicosin disk are resistant, < or = 10 mm, and susceptible, > or = 11 mm.

Actinobacillus Infections↗