Interpreting culture and susceptibility data in critical care: perks and pitfalls

Problem – The need for immediate, effective antimicrobial therapy in the critical care patient must be tempered by approaches which simultaneously minimize emergence of antimicrobial resistance. Ideally, therapy will successfully resolve clinical signs of infection, while eradicating infecting pathogens such that the risk of resistance is avoided. Increasing limitations associated with empirical antimicrobial choices direct the need for culture and susceptibility data as a basis of therapy. Even so, such in vitro data should be utilized within its limitations. Objectives – To demonstrate the attributes and limitations of patient and population culture and susceptibility (pharmacodynamic) data in the selection of antimicrobial drugs and to demonstrate the design of individualized dosing regimens based on integration of pharmacodynamic (PD) and pharmacokinetic (PK) data. Diagnosis – Limitations in culture and susceptibility testing begin with sample collection and continue through drug selection and dose design. Among the challenges in interpretation is discrimination between pathogens and commensals. Properly collected samples are critical for generation of data relevant to the patient's infection. Data are presented as minimum inhibitory concentrations (MICs). The MIC facilitate selection of the most appropriate drug, particularly when considered in the context of antimicrobial concentrations achieved in the patient at a chosen dose. Integration of MIC data with key PK data yields the C_max:MIC important to efficacy of concentration‐dependent drugs and T>MIC, which guides use of time‐dependent drugs. These indices are then used to design dosing regimens that are more likely to kill all infecting pathogens. In the absence of patient MIC data, population data (eg, MIC₉₀) may serve as a reasonable surrogate. Conclusions – Properly collected, performed, and interpreted culture and susceptibility data are increasingly important in the selection of and design of dosing regimens for antimicrobial drugs. Integration of PK and PD data as modified by host and microbial factors supports a hit hard, exit fast approach to therapy that will facilitate efficacy while minimizing resistance.     

Antimicrobial susceptibility patterns and sensitivity to tulathromycin in goat respiratory bacterial isolates

Bacterial pneumonia is a common and often life-threatening respiratory problem in both meat and dairy goats. Options for approved antibiotic therapy in goats to combat these bacterial infections are severely limited and frequently drugs must be used in an extra-label manner. Tulathromycin, a triamilide macrolide antimicrobial drug shown to be effective against swine and cattle respiratory bacterial agents, has been identified as a potentially useful drug in caprines. The present study was conducted to determine the susceptibility of recognized bacterial respiratory pathogens to commonly prescribed antimicrobials, with a particular emphasis on the efficacy of tulathromycin against these agents. Minimum inhibitory concentration (MIC) testing using microbroth dilution was performed on a collection of 45 Mannheimia haemolytica, 11 Pasteurella multocida, and 11 Bibersteinia trehalosi isolates from the lungs of goats with clinical pneumonia. To further characterize efficacy of tulathromycin against these pathogens, minimum bactericidal concentration (MBC) testing and kinetic killing assays were conducted. Most isolates were susceptible to the antimicrobials tested; however, increased resistance as demonstrated by higher MIC values was seen in all species to penicillin, in P. multocida to sulfadimethoxine, and in B. trehalosi to the tetracyclines. All isolates were susceptible to tulathromycin, which demonstrated a high killing efficiency in both bactericidal assays. Results of this study indicate that most goat pneumonic bacterial pathogens remain susceptible to commonly prescribed antibiotics, although some evidence of resistance was seen to certain drugs; and that tulathromycin is highly effective against goat respiratory pathogens which could make it a valuable medication in this species.     

Antimicrobial Activity of Tulathromycin and 14 Other Antimicrobials Against Virulent Rhodococcus equi In Vitro

This study determined the antimicrobial activity of tulathromycin against Rhodococcus equi in vitro. Ninety-eight virulent isolates of R. equi from equine clinical cases were examined, of which 20 isolates were macrolide resistant. A custom 96-well antimicrobial susceptibility testing plate was used, allowing 14 additional antimicrobials to be tested against R. equi. Isolates were cultured with various concentrations of antimicrobials, and minimal inhibitory concentration (MIC) values were determined. Tulathromycin was found to have poor activity in vitro against R. equi isolates susceptible or resistant to macrolides, with MIC50 and MIC90 values >64 ug/mL for all isolates. MIC values for other macrolides tested were similar to previously published data.     

Pharmacokinetic/pharmacodynamic relationships of antimicrobial drugs used in veterinary medicine

The rise in incidence of antimicrobial resistance, consumer demands and improved understanding of antimicrobial action has encouraged international agencies to review the use of antimicrobial drugs. More detailed understanding of relationships between the pharmacokinetics (PK) of antimicrobial drugs in target animal species and their action on target pathogens [pharmacodynamics (PD)] has led to greater sophistication in design of dosage schedules which improve the activity and reduce the selection pressure for resistance in antimicrobial therapy. This, in turn, may be informative in the pharmaceutical development of antimicrobial drugs and in their selection and clinical utility. PK/PD relationships between area under the concentration time curve from zero to 24 h (AUC(0-24)) and minimum inhibitory concentration (MIC), maximum plasma concentration (C(max)) and MIC and time during which plasma concentrations exceed the MIC have been particularly useful in optimizing efficacy and minimizing resistance. Antimicrobial drugs have been classified as concentration-dependent where increasing concentrations at the locus of infection improve bacterial kill, or time-dependent where exceeding the MIC for a prolonged percentage of the inter-dosing interval correlates with improved efficacy. For the latter group increasing the absolute concentration obtained above a threshold does not improve efficacy. The PK/PD relationship for each group of antimicrobial drugs is 'bug and drug' specific, although ratios of 125 for AUC(0-24):MIC and 10 for C(max):MIC have been recommended to achieve high efficacy for concentration-dependent antimicrobial drugs, and exceeding MIC by 1-5 multiples for between 40 and 100% of the inter-dosing interval is appropriate for most time-dependent agents. Fluoroquinolones, aminoglycosides and metronidazole are concentration-dependent and beta-lactams, macrolides, lincosamides and glycopeptides are time-dependent. For drugs of other classes there is limited and conflicting information on their classification. Resistance selection may be reduced for concentration-dependent antimicrobials by achieving an AUC(0-24):MIC ratio of greater than 100 or a C(max):MIC ratio of greater than 8. The relationships between time greater than MIC and resistance selection for time-dependent antimicrobials have not been well characterized.     

In vitro evaluation of topical biocide and antimicrobial susceptibility of Staphylococcus pseudintermedius from dogs

Background – Staphylococcus pseudintermedius is an important canine pathogen, and the emergence and widespread dissemination of meticillin‐resistant strains (MRSP) is of significant concern. Multidrug‐resistant infections may require alternative approaches, such as the use of topical therapy. There is minimal information about the in vitro susceptibility of meticillin‐susceptible S. pseudintermedius (MSSP) and MRSP to biocides and topical antimicrobials. Hypothesis/Objectives – The hypothesis was that clinical isolates of MSSP and MRSP would not have universal susceptibility to topical biocides and antimicrobials. The goal of this study was to assess the susceptibility of a collection of S. pseudintermedius isolates to selected antimicrobials and biocides. Animals – The study was performed on clinical isolates of MSSP and MRSP from dogs with skin and soft tissue infections collected throughout North America between 2006 and 2008. Methods – The minimal inhibitory concentrations (MICs) of chlorhexidine digluconate, benzalkonium chloride, triclosan, accelerated hydrogen peroxide, geranium oil, tea tree oil and grapefruit seed extract were tested for 25 MRSP and 25 MSSP isolates from dogs using the agar dilution method. The MICs of fusidic acid, bacitracin and mupirocin were determined using Etests. Results – Triclosan demonstrated excellent activity against all bacterial isolates, with no growth at the lowest concentration evaluated (MIC ≤ 0.5 μg/mL). Conversely, grapefruit seed extract did not inhibit growth at the highest concentration tested (MIC > 3.84 μg/mL). All isolates were susceptible to mupirocin, fusidic acid and bacitracin. There were no significant differences noted in the range, MIC₅₀ or MIC₉₀ between MSSP and MRSP isolates. Conclusions and clinical importance – While isolates were susceptible to most of the tested compounds, universal susceptibility to all compounds with potential antimicrobial activity cannot be assumed, and specific testing is required.     

Antimicrobial susceptibility of Streptococcus suis isolated from clinically healthy swine in Brazil

Streptococcus suis is an important pathogen in the swine industry. This study is the first to report on the antimicrobial susceptibility of S. suis isolated from clinically healthy pigs in Brazil; the fourth major pork producer in the world. The antimicrobial susceptibility of 260 strains was determined by disc diffusion method. Strains were commonly susceptible to ceftiofur, cephalexin, chloramphenicol, and florfenicol, with more than 80% of the strains being susceptible to these antimicrobials. A high frequency of resistance to some of the antimicrobial agents was demonstrated, with resistance being most common to sulfa-trimethoprim (100%), tetracycline (97.69%), clindamycin (84.61%), norfloxacin (76.92%), and ciprofloxacin (61.15%). A high percentage of multidrug resistant strains (99.61%) were also found. The results of this study indicate that ceftiofur, cephalexin, and florfenicol are the antimicrobials of choice for empirical control of the infections caused by S. suis.     

鸡源A型产气荚膜梭菌致病性及药物疗效分析

本研究旨在调查规模化养鸡场内鸡源产气荚膜梭菌（Clostridium perfringens，CP）的致病性和耐药性，并评价阿维拉霉素和磷酸泰乐菌素预防CP感染鸡群发生坏死性肠炎（necrotizing enteritis，NE）的效果，为鸡NE的防治提供指导。在河北、山西两地选择有CP引起NE发病史的规模化养鸡场，随机采集新鲜粪便，分离CP，并通过多重PCR测定其毒素型。选定3个不同养殖场分离到的A型CP，以10⁹CFU·只^-1的剂量，连续5 d经灌胃的方式感染14日龄SPF鸡，观察肠道病变和NE发生情况，评价分离菌株的致病力。使用微量肉汤稀释法测定分离到的CP对阿维拉霉素、林可霉素和磷酸泰乐菌素的最小抑菌浓度（minimal inhibitory concentration，MIC）。根据MIC结果，选择药物敏感性较好的两种药物对因CP引起NE发病的鸡群中未出现临床症状的鸡进行预防试验，观察精神食欲、腹泻症状、肠道病变情况，统计CP检出率和NE发生率，评价两种药物预防效果。结果显示：自753份鸡粪便样品分离到91株CP，且毒素型全部为A型。攻毒试验结果显示：A、B、C组攻毒组NE病变发生率均显著高于未攻毒组D组（P<0.05），攻毒组肠道病变评分均显著高于未攻毒组（P<0.05）。与未攻毒组相比，攻毒组出现明显的腹泻症状和肠道病变，差异显著（P<0.05），3株CP都可以引起鸡NE。MIC结果表明：阿维拉霉素、林可霉素和磷酸泰乐菌素的MIC范围分别是0.25～4、0.125～128和0.25～32 μg·mL^-1。药物疗效试验结果表明：通过拌料连续21 d给予阿维拉霉素预混剂，给药期间及停药后1周可保护鸡群，防止出现NE症状或防止病变恶化，显著降低NE发生率、NE病变评分以及CP检出率（P<0.05）。通过拌料连续7 d给予磷酸泰乐菌素预混剂，效果与阿维拉霉素预混剂相当，但停药14 d后，6只鸡（6/11）又出现NE症状。目前，河北、山西省部分规模化鸡养殖场内流行的CP多为A型，并且可以引起NE，同时，A型CP对阿维拉霉素和磷酸泰乐菌素仍较敏感，其预混剂用于发病鸡群的预防效果较好。     

A survey of the fecal bacteria of bison (Bison bison) for potential pathogens and antimicrobial susceptibility of bison-origin E. coli

An observational study determined the normal fecal bacterial flora of clinically healthy bison, detected the presence of common potential zoonotic pathogens, and determined the antimicrobial susceptibility of isolated E. coli strains. Ninety-six fecal samples from 10 captive herds were cultured for aerobic, anaerobic, facultative, and microaerophillic bacteria. Nineteen major genera of gram-positive and 8 genera of gram-negative bacteria were identified. Salmonella spp. were not detected but some of the isolated bacteria are potential gastrointestinal pathogens. Minimum inhibitory concentrations (MIC) of 24 antimicrobials were determined for the E. coli isolated. Nearly all were susceptible to 23 of the 24 antimicrobials but there was a reduced susceptibility to sulphonamide. There were fewer resistant strains than were reported in recent studies of generic E. coli from cattle living in the same area.     

Antimicrobial use in the surgical patient.

Antimicrobials are often used in the surgical patient in an effort to prevent infection (prophylactic) or to treat established infection (therapeutic). To be effective, prophylactic antimicrobials at appropriate concentrations must be present in tissues at the surgical site at the time of contamination to prevent bacterial growth and subsequent infection. Therapeutic antimicrobials are used to treat established localized or systemic infection. Selection of antimicrobial agents for prophylactic or therapeutic use should be based on knowledge of expected flora, ability of the antimicrobial to reach the target tissue at appropriate concentrations, bacterial resistance patterns, drug pharmacokinetics, and culture and susceptibility testing results (therapeutic use). Failure of antimicrobial therapy to prevent or treat infection in the surgical patient may result from poor antimicrobial selection, inappropriate dosage or frequency, or inappropriate duration of therapy.     

Comparison of methods for antimicrobial susceptibility testing and MIC values for pleuromutilin drugs for Brachyspira hyodysenteriae isolated in Germany

In Germany treatment of swine dysentery is hampered by Brachyspira hyodysenteriae strains showing elevated MIC values to the few antibiotics licensed. Therefore, susceptibility testing of clinical isolates is an important service to the swine practitioner. This study compares the established agar dilution procedure for antimicrobial susceptibility testing of this fastidious anaerobe to the broth microdilution test newly developed [Anim. Health Res. 2 (2001) 59; Vet. Microbiol. 84 (2002) 123; J. Clin. Microbiol. 41 (2003) 2596]. A total of 221 isolates were examined twice with either test procedure using tiamulin and valnemulin as antibiotics. Both methods gave reproducible results, and the MIC values for the reference strains B. hyodysenteriae B204 and Staphylococcus aureus ATCC 29213 corresponded to previously published data. However, the results for individual strains differed significantly for both tests (P < 0.001) with MIC values being on average one dilution step lower in the broth dilution method. The 221 strains used for comparing test procedures were isolated between 1989 and 2001. An additional 102 strains isolated in 2002 were tested only with the broth dilution procedure. A significant rise in the average MIC value for both pleuromutilins could be demonstrated when comparing earlier isolates to those from 2000 to 2001 (P < 0.05), while in 2002 the average MIC significantly decreased when compared to the value in 2000 (P < 0.05). However, strains with MIC values for tiamulin as high as 8 microg/ml (broth dilution) could still be isolated.     

Antimicrobial susceptibility of Swedish, Norwegian and Danish isolates of Clostridium perfringens from poultry, and distribution of tetracycline resistance genes

This study was undertaken to determine the in vitro susceptibility of Clostridium perfringens, isolated from poultry to antimicrobials used in poultry production. The minimal inhibitory concentration (MIC) of eight antimicrobials, including the ionophoric coccidiostat narasin, was determined for 102 C. perfringens isolates, 58 from Sweden, 24 from Norway and 20 from Denmark. Susceptibility to each antimicrobial compound was determined by broth microdilution. The isolates were obtained from broilers (89), laying hens (9) and turkeys (4), affected by necrotic enteritis (NE) or by C. perfringens associated hepatitis (CPH), and from healthy broilers. All strains, regardless of origin, proved inherently susceptible to ampicillin, narasin, avilamycin, erythromycin and vancomycin. A low frequency of resistance to virginiamycin and bacitracin was also found. Resistance to tetracycline was found in strains isolated in all three countries; Sweden (76%), Denmark (10%) and Norway (29%). In 80% of the tetracycline-resistant isolates, the two resistance genes tetA(P) and tetB(P) were amplified by PCR whereas in 20% only the tetA(P) gene was detected. No tetM gene amplicon was obtained from any of the tetracycline-resistant isolates. The uniform susceptibility to narasin revealed in this study shows that the substance can still be used to control clostridiosis. In this study, C. perfringens also showed a low degree of resistance to most other antimicrobials tested. Despite the small amounts of tetracycline used in poultry, a considerable degree of resistance to tetracycline was found in C. perfringens isolates from Swedish broilers.     

Epidemiologic cutoff values for antimicrobial agents against Aeromonas salmonicida isolates determined by frequency distributions of minimal inhibitory concentration and diameter of zone of inhibition data

OBJECTIVE: To develop epidemiologic cutoff values by use of frequency distributions for susceptibility to 4 antimicrobial agents when tested against a representative population of a major aquaculture pathogen, Aeromonas salmonicida. SAMPLE POPULATION: 217 typical and atypical A salmonicida isolates obtained from 20 states and 12 countries. PROCEDURES: Species identification of A salmonicida isolates was confirmed by detection of specific nucleotide sequences by use of a PCR assay. Minimal inhibitory concentration (MIC) and diameter of the zone of inhibition for oxytetracycline, ormetoprim-sulfadimethoxine, oxolinic acid, and florfenicol were determined for each isolate in accordance with standardized antimicrobial susceptibility testing methods that have been approved by the Clinical and Laboratory Standards Institute for bacterial isolates from aquatic animals. Susceptibility data were tabulated in a scattergram and analyzed by use of error rate bounding. RESULTS: Susceptibility tests for oxytetracycline, ormetoprim-sulfadimethoxine, and oxolinic acid revealed 2 distinct populations of bacteria. Isolates tested against florfenicol clustered into a single population. Oxolinic acid susceptibility data revealed higher MICs in the non-United States A salmonicida isolates. Slow-growing (atypical) A salmonicida isolates were generally more susceptible than typical isolates for all antimicrobials, except oxolinic acid. CONCLUSIONS AND CLINICAL RELEVANCE: Use of frequency distributions of susceptibility results to develop epidemiologic cutoff values appears to be applicable to aquatic isolates. Frequency distributions of susceptibility results for A salmonicida revealed clear divisions between isolate susceptibilities. This type of data, considered in conjunction with pharmacokinetic and efficacy data, may be useful for developing clinical breakpoints for use in aquaculture.     

Repurposing Ionophores as novel antimicrobial agents for the treatment of bovine mastitis caused by Gram‐positive pathogens

Increasing reports of multidrug‐resistant bacterial infections in animals has created a need for novel antimicrobial agents that do not promote cross‐resistance to critically important antimicrobial classes used in human medicine. In response to the recent emergence of antimicrobial resistance in several bovine mastitis pathogens, in vitro antimicrobial susceptibility was determined for four polyether ionophores (lasalocid, monensin, narasin and salinomycin) against Staphylococcus spp. and Streptococcus spp. isolated from clinical cases. In addition, erythrocyte haemolysis and WST ‐1 cell proliferation assays were used to assess in vitro mammalian cell cytotoxicity and biofilm susceptibility testing was performed using the minimum biofilm eradication concentration (MBEC ?) biofilm assay. Lasalocid, monensin, narasin and salinomycin exhibited bacteriostatic antimicrobial activity against all pathogens tested, including methicillin‐resistant staphylococci, with MIC ₉₀ values <16 μg/ml. Narasin and monensin displayed the least toxicity against mammalian cell lines and all compounds significantly reduced viable cell numbers in a Staphylococcus aureus biofilm. Based on in vitro characterization, all four ionophores offer potentially novel treatments against bovine mastitis but in vivo studies will be essential to determine whether acceptable safety and efficacy is present following intramammary administration.     

In vitro antimicrobial inhibition profiles of Mycoplasma bovis isolates recovered from various regions of the United States from 2002 to 2003.

Antimicrobial therapy continues to be important in reducing losses due to pneumonic forms of Mycoplasma bovis disease in beef and dairy calves. Although M. bovis diseases have been documented as frequent and economically important in the United States, there are no published reports on the antimicrobial activity of approved compounds against US strains. In this study, the authors report on the activity of 9 different antimicrobials against 223 recently recovered isolates of M. bovis. These isolates represent accessions from 5 geographic regions of the United States and were grouped by 4 tissues of origin (milk, respiratory, joint, or ear and eye). A broth microdilution test was used to determine minimum inhibitory concentration (MIC) values by reading redox changes detected in broth with alamarBlue (resazurin) indicator. For each antimicrobial, the median, MIC50, MIC90, mode, and range were calculated, and the values used for comparisons. In the absence of accepted breakpoint values, published MIC cutoff values for animal mycoplasmas as well as Clinical Laboratory Standards Institute interpretive criteria were used as a reference to define in vitro activity. The MIC values from active antimicrobials were found to distribute independently of region of origin of the isolates or of tissue of origin. Enrofloxacin, florfenicol, and spectinomycin were found to be active compounds in vitro. Oxytetracycline and chlortetracycline were active against more than half of the isolates. Very few isolates were inhibited by tilmicosin and none by erythromycin, ampicillin, or ceftiofur. The antimicrobial profiles determined for these US strains were remarkably similar to those reported for European isolates. However, unlike in Europe, there appears to be no diversity of profiles when US isolates are grouped by region or tissue of origin.     

Antimicrobial resistance and genotypic characterization of coagulase-negative staphylococci over the dry period

Coagulase-negative staphylococci (CNS) have become the most frequently isolated organisms from bovine intramammary infections in recent years. While antimicrobial resistance (AR) is not considered a major problem among mastitis pathogens, concerns over emerging AR in general are increasing worldwide. Little information exists about the association between AR and one of the most common mastitis control measures, antibiotic dry cow therapy. The primary objective of the current study was to determine the prevalence of AR in CNS isolated before and after antimicrobial dry cow therapy. An additional objective was to genotypically characterize selected CNS isolates using pulsed-field gel electrophoresis (PFGE), to assess diversity and persistence of organisms over the dry period. Resistance against 10 antimicrobials was determined using a broth microdilution method and compared between CNS isolates collected at dry-off and at calving and from cows treated or not treated with intramammary antimicrobial products at dry-off (752 cows in total). Results suggested that increasing age of a cow and dry cow treatment when combined with high milk somatic cell count at dry-off and positive clinical mastitis history, were associated with increased AR to most beta-lactam antimicrobials and sulfadimethoxine. PFGE results suggested considerable diversity among the tested isolates as well as some clusters within cows and herds. PFGE would be useful in distinguishing between potentially persisting infections and cures and reinfections with different CNS strains.     

Overview of the use of antimicrobial drugs for the treatment of bacterial infections in horses

The use of antimicrobials in veterinary medicine is under great scrutiny with the emergence of antimicrobial resistance in the human population. Equine veterinarians rely on antimicrobials as an essential tool for the treatment of infections in horses, but there is much criticism of some use, particularly prophylaxis. While the appropriate use of antimicrobials can be justified in equine medicine, the misuse cannot. The definition of appropriate use is complex and involves the indication for therapy, antimicrobial selection, dosing regimen and timing and route of administration, duration of therapy and modification of therapy based on microbial susceptibility and clinical response. The aim of this article is to provide guidance on these factors to assist equine veterinarians in determining what constitutes appropriate antimicrobial use in horses.     

细菌对抗菌药物敏感性测定的新方法

防突变浓度指防止细菌的耐药突变株被选择性富集所需的最低药物浓度,作为一种细菌敏感性测定的新方法,防突变浓度可用于预测及评估抗菌药物的防突变能力,从而使临床用药更为合理。文章就防突变浓度的测定方法、意义及其与最小抑菌浓度(MIC)、药代动力学、药效动力学的关系进行了综述,为掌握抗菌药物敏感性测定的新方法及合理使用抗菌药提供参考。     

Infection of the subcutis and skin of cats with rapidly growing mycobacteria: a review of microbiological and clinical findings.

Mycobacteria were isolated and characterised from 49 cats with extensive infections of the subcutis and skin. Cats were generally between 3 and 10 years of age, and female cats were markedly over-represented. All isolates were rapid-growers and identified as either Mycobacteria smegmatis (40 strains) or M fortuitum (nine strains). On the basis of Etest for minimum inhibitory concentration and/or disc diffusion susceptibility testing, all strains of M smegmatis were susceptible to trimethoprim while all strains of M fortuitum were resistant. M smegmatis strains were typically susceptible to doxycycline, gentamicin and fluoroquinolones but not clarithromycin. All M fortuitum strains were susceptible to fluoroquinolones, and often also susceptible to gentamicin, doxycycline and clarithromycin. Generally, M smegmatis strains were more susceptible to antimicrobial agents than M fortuitum strains. Treatment of mycobacterial panniculitis involves long courses of antimicrobial agents, typically of 3-6 months, chosen on the basis of in vitro susceptibility testing and often combined with extensive surgical debridement and wound reconstruction. These therapies will result in effective cure of the disease. One or a combination of doxycycline, ciprofloxacin/enrofloxacin or clarithromycin are the drugs of choice for long-term oral therapy.     

Evaluation of changes in antimicrobial susceptibility patterns of Pasteurella multocida subsp multocida isolates from pigs in Spain in 1987-1988 and 2003-2004

OBJECTIVE: To determine the susceptibility of strains of Pasteurella multocida subsp multocida isolated from lung specimens of pigs with pneumonia to 20 antimicrobials and to evaluate the emergence of resistance to those antimicrobials in Spain during the past 2 decades. SAMPLE POPULATION: 63 isolates recovered from 1987 to 1988 and 132 isolates recovered from 2003 to 2004. PROCEDURE: A broth microdilution method was used to determine minimal inhibitory concentration (MIC) range and values for MIC50 and MIC90. Resistance of a strain to an antimicrobial agent was determined by use of the breakpoint value when available. RESULTS: Isolates were generally susceptible to penicillin, ampicillin, ceftiofur, gentamicin, apramycin, neomycin, spectinomycin, chlortetracycline, erythromycin, tilmicosin, enrofloxacin, and florfenicol, and most isolates were resistant to clindamycin, tylosin tartrate, and tiamulin regardless of the time period. A substantial increase in resistance to sulfa-chlorpiridazine, sulfadimethoxine, sulfathiazole, and trimethoprim-sulfamethoxazole was observed, and a minor increase in resistance to oxytetracycline was also detected. Several multiresistance patterns were observed, most frequently among isolates recovered in the 2003 to 2004 interval. CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur, florfenicol, and enrofloxacin are recommended for treatment of infections caused by P multocida subsp multocida in Spain. Increased frequency of resistance to oxytetracycline and sulfonamide drugs may be a contraindication for their use.