Effects of quantitative trait loci and the myostatin locus on trace and macro elements (minerals) in bovine liver, muscle and kidney.

A quantitative trait locus (QTL) study of the concentrations of 14 trace and macro elements (minerals) in tissues of beef cattle was conducted in New Zealand. Back-cross calves with Jersey and Limousin ancestry (202 heifers and 211 steers) were generated using first-cross sires. This paper reports on testing for effects of QTL on the concentrations of minerals in liver, kidney and muscle in cattle at slaughter, following a growth phase during which rearing and finishing stages were on pasture. Fifteen QTL were identified (P < 0.05) on a genome-wide basis in combined-sire and within-sire analyses. In addition, the possible effect of the Limousin myostatin F94L allele was tested by fitting each calf's myostatin genotype, and 16 QTL were identified. Twelve were in common with those QTL identified previously, comprising six affecting the liver (copper and zinc, on two chromosomes each; plus iron and molybdenum), three affecting the kidney (calcium, copper and iron), and three affecting muscle (iron, strontium and zinc).

Potential of in-plant intramuscular fat predictions to enable sheep breeders to incorporate consumer preferences in breeding programmes.

The inclusion of eating quality traits in sheep genetic improvement programmes is desirable. Intramuscular fat (IMF) plays a key role in ensuring consumer satisfaction when eating lamb, but genetic progress for IMF is constrained by a lack of routine data collection. This study investigated the potential for IMF predictor traits to substitute for measured IMF in genetic improvement programmes. Carcass and predicted IMF (near-infrared estimated IMF and marbling score) data were available on 10,113 New Zealand lambs, 1678 of which also had measured chemical IMF on a slice of M. longissimus lumborum on which the predictions of IMF had been made. Genetic antagonisms were observed between carcass lean traits and IMF. The genetic correlation between the predictors and measured IMF approached one, indicating that predictors of IMF can be used in genetic improvement programmes. Through using selection indexes, simultaneous increases in IMF and the existing terminal selection index are possible, provided all traits are measured. This study highlights the importance and potential of predicted IMF to achieve genetic improvement in traits of importance to consumers.

Can we have our steak and eat it: The impact of breeding for lowered environmental impact on yield and meat quality in sheep.

Global agreements in place to reduce methane emissions in livestock are a potential threat to food security. Successful but independent breeding strategies for improved production and lower methane are in place. The unanswered questions are whether these strategies can be combined and how they impact one another, physically and economically. The New Zealand economy is largely dependent on pastoral agriculture from grazing ruminants. The sheep industry produces ∼20 million lamb carcasses for export each year primarily from grass. Methane emitted from the fermentation of forage by grazing ruminants accounts for one-third of all New Zealand's greenhouse gas emissions. Here, we use sheep selection lines bred for divergent methane production and large numbers of their relatives to determine the genetic and phenotypic correlations between enteric methane emissions, carcass yield, and meat quality. The primary objectives were to determine whether previously shown physiological differences between methane selection lines (differing by ∼12% in methane) result in a negative impact on meat production and quality by measuring close relatives. The results show no negative effects of breeding for lowered methane on meat and carcass quality. Gross methane emissions were highly correlated with liveweight and measures of carcass weight and negatively correlated with dressing-out percentage and fat yield (GR). Trends were similar but not significant for methane yield (g CH4/kg DMI). Preliminary evidence, to date, shows that breeding for low methane may result in animals with higher lean yields that are economically favorable even before carbon costs and environmental benefits are taken into account. These benefits were seen in animals measured for methane on fixed intakes and require validation on intakes that are allowed to vary.

Genetic mapping of quantitative trait loci for meat quality and muscle metabolic traits in cattle.

A whole-genome scan was carried out in New Zealand and Australia to detect quantitative trait loci (QTL) for live animal and carcass composition traits and meat quality attributes in cattle. Backcross calves (385 heifers and 398 steers) were generated, with Jersey and Limousin backgrounds. The New Zealand cattle were reared and finished on pasture, whilst Australian cattle were reared on grass and finished on grain for at least 180 days. This paper reports on meat quality traits (tenderness measured as shear force at 4-5 ages on two muscles as well as associated traits of meat colour, pH and cooking loss) and a number of metabolic traits. For meat quality traits, 18 significant QTL (P < 0.05), located in nine linkage groups, were detected on a genome-wise basis, in combined-sire (seven QTL) or within-sire analyses (11 QTL). For metabolic traits, 11 significant QTL (P < 0.05), located in eight linkage groups, were detected on a genome-wise basis, in combined-sire (five QTL) or within-sire analyses (six QTL). BTA2 and BTA3 had QTL for both metabolic traits and meat quality traits. Six significant QTL for meat quality and metabolic traits were found at the proximal end of chromosome 2. BTA2 and BTA29 were the most common chromosomes harbouring QTL for meat quality traits; QTL for improved tenderness were associated with Limousin-derived and Jersey-derived alleles on these two chromosomes, respectively.

ENSO feedback drives variations in dieback at a marginal mangrove site.

Ocean-atmosphere climatic interactions, such as those resulting from El Niño Southern Oscillation (ENSO) are known to influence sea level, sea surface temperature, air temperature, and rainfall in the western Pacific region, through to the north-west Australian Ningaloo coast. Mangroves are ecologically important refuges for biodiversity and a rich store of blue carbon. Locations such as the study site (Mangrove Bay, a World Heritage Site within Ningaloo Marine Park and Cape Range National Park) are at the aridity range-limit which means trees are small in stature, forests small in area, and are potentially susceptible to climate variability such as ENSO that brings lower sea level and higher temperature. Here we explore the relationship between mangrove dieback, and canopy condition with climatic variables and the Southern Oscillation Index (SOI)-a measure of ENSO intensity, through remote sensing classification of Landsat satellite missions across a 29 year period at a north-west Australian site. We find that the SOI, and seasonal mean minimum temperature are strongly correlated to mangrove green canopy (as indicator of live canopy) area. This understanding of climate variations and mangrove temporal heterogeneity (patterns of abundance and condition) highlights the sensitivity and dynamics of this mangrove forest and recommends further research in other arid and semi-arid tropical regions at mangrove range-limits to ascertain the extent of this relationship.

Quantitative trait loci for organ weights and adipose fat composition in Jersey and Limousin back-cross cattle finished on pasture or feedlot.

A QTL study of live animal and carcass traits in beef cattle was carried out in New Zealand and Australia. Back-cross calves (385 heifers and 398 steers) were generated, with Jersey and Limousin backgrounds. This paper reports on weights of eight organs (heart, liver, lungs, kidneys, spleen, gastro-intestinal tract, fat, and rumen contents) and 12 fat composition traits (fatty acid (FA) percentages, saturated and monounsaturated FA subtotals, and fat melting point). The New Zealand cattle were reared and finished on pasture, whilst Australian cattle were reared on grass and finished on grain for at least 180 days. For organ weights and fat composition traits, 10 and 12 significant QTL locations (P<0.05), respectively, were detected on a genome-wide basis, in combined-sire or within-sire analyses. Seven QTL significant for organ weights were found at the proximal end of chromosome 2. This chromosome carries a variant myostatin allele (F94L), segregating from the Limousin ancestry, and this is a positional candidate for the QTL. Ten significant QTL for fat composition were found on chromosomes 19 and 26. Fatty acid synthase and stearoyl-CoA desaturase (SCD1), respectively, are positional candidate genes for these QTL. Two FA QTL found to be common to sire groups in both populations were for percentages of C14:0 and C14:1 (relative to all FAs) on chromosome 26, near the SCD1 candidate gene.

Quantitative trait loci for live animal and carcass composition traits in Jersey and Limousin back-cross cattle finished on pasture or feedlot.

A quantitative trait locus (QTL) study was carried out in two countries, recording live animal and carcass composition traits. Back-cross calves (385 heifers and 398 steers) were generated, with Jersey and Limousin breed backgrounds. The New Zealand cattle were reared on pasture to carcass weights averaging 229 kg, whilst the Australian cattle were reared on grass and finished on grain (for at least 180 days) to carcass weights averaging 335 kg. From 11 live animal traits and 31 carcass composition traits respectively, 5 and 22 QTL were detected in combined-sire analyses, which were significant (P < 0.05) on a genome-wise basis. Fourteen significant traits for carcass composition QTL were on chromosome 2 and these were traits associated with muscling and fatness. This chromosome carried a variant myostatin allele (F94L), segregating from the Limousin ancestry. Despite very different cattle management systems between the two countries, the two populations had a large number of QTL in common. Of the 18 traits which were common to both countries, and which had significant QTL at the genome-wise level, eight were significant in both countries.

Heritability of ram mating success in multi-sire breeding situations.

Multi-sire mating of a mob of ewes is commonly used in commercial sheep production systems. However, ram mating success (defined as the number of lambs sired by an individual) can vary between rams in the mating group. If this trait was repeatable and heritable, selection of rams capable of siring larger numbers of lambs could reduce the number of rams required for mating and ultimately lead to increased genetic gain. However, genetic correlations with other productive traits, such as growth and female fertility, could influence the potential for ram mating success to be used as a selection trait. In order to investigate this trait, parentage records (including accuracy of sire assignment) from 15 commercial ram breeding flocks of various breeds were utilised to examine the repeatability and heritability of ram mating success in multi-sire mating groups. In addition, genetic and phenotypic correlations with growth and female fertility traits were estimated using ASReml. The final model used for the ram mating success traits included age of the ram and mating group as fixed effects. Older rams (3+years old) had 15% to 20% greater mating success than younger rams (1 or 2 years of age). Increasing the stringency of the criteria for inclusion of both an individual lamb, based on accuracy of sire assignment, or a whole mating group, based on how many lambs had an assigned sire, increased repeatability and heritability estimates of the ram mating success traits examined. With the most stringent criteria employed, where assignment of sire accuracy was >0.95 and the total number of lambs in the progeny group that failed to have a sire assigned was<0.05, repeatability and heritability for loge(number of lambs) was 0.40±0.09 and 0.26±0.12, respectively. For proportion of lambs sired, repeatability and heritability were both 0.30±0.09. The two ram mating traits (loge(nlamb) and proportion) were highly correlated, both phenotypically and genetically (0.88±0.01 and 0.94±0.06, respectively). Both phenotypic and genetic correlations between ram mating success and growth and other female fertility traits were low and non-significant. In conclusion, there is scope to select rams capable of producing high numbers of progeny and thus increase selection pressure on rams to increase genetic gain.

Genetic factors affecting antibody responses to four species of nematode parasite in Romney ewe lambs.

Serum levels of antibodies (Ab) and immunoglobulin G1 (IgG1) to the larval (L3) stage of the internal parasites Cooperia curticei and Trichostrongylus colubriformis and levels of Ab to the L3 stages of Haemonchus contortus and Ostertagia circumcincta were determined in 1432 Romney ewe lambs which were born on one farm in 1990 and 1991 and were the progeny of 63 rams. The objectives were to estimate heritabilities of, and genetic correlations among, the serum concentrations in newly weaned lambs under commercial conditions and to estimate genetic correlations of Ab and IgG1 with production traits. Lambs were exposed to a natural parasite challenge on pasture, following an anthelmintic drench at weaning. Blood and faecal samples from 4- to 6-month-old lambs were then taken when the mean faecal nematode egg count of a monitor group reached 800-1500 eggs g-1. Heritabilities for the serum levels of the four Abs ranged from 0.25 +/- 0.05 to 0.37 +/- 0.06. Heritabilities for the level of IgG1 developed against C. curticei was 0.19 +/- 0.04 and against T. colubriformis, 0.18 +/- 0.05. Genetic correlations between Abs for the 4 species were high, averaging 0.84, and between the two IgG1s it was 0.82. The genetic correlations between Ab or IgG1 levels and weight or gain traits were negative (for the 6 significant values out of 18), with yearling fleece weight positive (for the 2 significant values out of 6), whilst those with loge faecal egg count were all negative (average -0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal fluid values in the term neonate.

BACKGROUND: Cerebrospinal fluid (CSF) values in the noninfected neonate are not well-delineated. Studies analyzing these values are inconsistent in the criteria used to define the noninfected population. The purpose of our study was to examine CSF values in neonates in the first 30 days of life in whom infection was more thoroughly excluded than in previous reports. Stringent inclusion criteria defined the noninfected population, and the recently available polymerase chain reaction (PCR) for enteroviruses was used in addition to cultures to help exclude viral disease. Results were also stratified by age in weeks to evaluate for any variability that occurs in CSF values during the first month of life. METHODS: Neonates were selected from subjects enrolled in two studies on aseptic meningitis. Noninfected infants were identified by the following criteria: (1) atraumatic lumbar puncture (< or = 1000 red blood cells/mm3); (2) no antibiotic therapy before lumbar puncture; (3) sterile blood, CSF and urine bacterial cultures; (4) negative CSF viral culture; and (5) negative CSF PCR for enteroviruses. RESULTS: The mean +/- SD total CSF white blood cell count for 108 noninfected neonates was 7.3 +/- 14/mm3 (95% confidence interval 6.6 to 8.0/mm3) with a median of 4/mm3 and a range of 0 to 130/mm3. There were no significant differences in the mean CSF white blood cell counts among age categories. CONCLUSIONS: The application of stringent inclusion criteria and the use of the PCR yielded a population of infants that better represents the noninfected neonate than earlier reports. These values can be used for reference in evaluating the febrile or ill neonate.

Escherichia coli septicemia in nonperforated appendicitis.

OBJECTIVE: To determine the association between nonperforated appendicitis and Escherichia coli septicemia, and the frequency with which blood cultures are obtained in the clinical setting of appendicitis. DESIGN: Three case reports of E coli septicemia and nonperforated appendicitis and a retrospective survey. SETTING: Children's Medical Center, Dallas, Tex, a primary care and tertiary referral center. PATIENTS: All children admitted in a 2-year period with a diagnosis of appendicitis. INTERVENTIONS: None. RESULTS: Preoperative blood cultures were obtained in 20 (21%) of 96 patients with histologic evidence of appendicitis. Fifty percent of the patients had gross or microscopic evidence of appendiceal perforation. Twelve (25%) of the 48 patients with perforated appendicitis had blood cultures obtained before the initiation of antimicrobial therapy, and in two of these patients (17%) the results were positive. Blood cultures were drawn before antibiotic therapy in four (8%) of the 48 patients with nonperforated appendicitis, and in two of these the results were positive. The blood culture isolates (coagulase-negative Staphylococcus and E coli) were the same in both groups. CONCLUSIONS: Nonperforated appendicitis and septicemia may be more common than formerly appreciated. Only a prospective study can determine the true incidence of septicemia in children with perforated or nonperforated appendicitis.

What every pediatrician should know about infectious mononucleosis in adolescents.

Infectious mononucleosis (IM) is one of the most common diseases occurring during adolescence. Appreciation of IM's varied clinical presentations, its differential diagnosis, and the difficulties involved in making the laboratory diagnosis will enable clinicians to treat teenagers more effectively in their office practices.

Heritability estimates of methane emissions from sheep.

The objective of this study was to determine the genetic parameters of methane (CH4) emissions and their genetic correlations with key production traits. The trial measured the CH4 emissions, at 5-min intervals, from 1225 sheep placed in respiration chambers for 2 days, with repeat measurements 2 weeks later for another 2 days. They were fed in the chambers, based on live weight, a pelleted lucerne ration at 2.0 times estimated maintenance requirements. Methane outputs were calculated for g CH4/day and g CH4/kg dry matter intake (DMI) for each of the 4 days. Single trait models were used to obtain estimates of heritability and repeatability. Heritability of g CH4/day was 0.29 ± 0.05, and for g CH4/kg DMI 0.13 ± 0.03. Repeatability between measurements 14 days apart were 0.55 ± 0.02 and 0.26 ± 0.02, for the two traits. The genetic and phenotypic correlations of CH4 outputs with various production traits (weaning weight, live weight at 8 months of age, dag score, muscle depth and fleece weight at 12 months of age) measured in the first year of life, were estimated using bivariate models. With the exception of fleece weight, correlations were weak and not significantly different from zero for the g CH4/kg DMI trait. For fleece weight the phenotypic and genetic correlation estimates were -0.08 ± 0.03 and -0.32 ± 0.11 suggesting a low economically favourable relationship. These results indicate that there is genetic variation between animals for CH4 emission traits even after adjustment for feed intake and that these traits are repeatable. Current work includes the establishment of selection lines from these animals to investigate the physiological, microbial and anatomical changes, coupled with investigations into shorter and alternative CH4 emission measurement and breeding value estimation techniques; including genomic selection.

Responses of prolactin and hair growth to selection for age at puberty in Angus cattle.

A trial was carried out over a 7-year period (1999 to 2005 calf crops) to compare indicators of seasonality in Angus cattle, which were part of a long-term genetic selection experiment. Divergent selection was applied for early ('AGE-') or late ('AGE+') age at puberty (AP) in heifers, and selection lines differed over the 7-year period by 62 days (15% of the mean). The primary measures of seasonality studied in 629 heifer progeny (59 sire groups) were serum concentration of prolactin (PRL), and winter and summer hair growth. Serial samples were obtained for PRL from 11 to 18 months of age, and data were analysed with adjustment for cortisol concentration. Using restricted maximum likelihood procedures with an animal model, heritability estimates were: AP, 0.26 ± 0.03; log(e)PRL concentration, 0.23 ± 0.07; log(e)cortisol concentration, 0.22 ± 0.07; hair weight, 0.21 ± 0.04; and hair length, 0.09 ± 0.05. Corresponding repeatability estimates for the last four traits were 0.49 ± 0.03, 0.38 ± 0.03, 0.21 ± 0.04, and 0.64 ± 0.02, respectively. The genetic correlation between AP and log(e)PRL concentration was estimated at -0.29 ± 0.13 (P < 0.05). PRL concentration in the AGE- line after passing through puberty was 11 ± 5% lower than in the AGE+ line (P < 0.05). Line effects were not significant for hair weight or hair length. It was concluded that divergent selection for AP changed PRL concentration, which may partly reflect sensitivity to changing day length.

The effect of Johne's disease on production traits in Romney, Merino and Merino x Romney-cross ewes.

AIM: To quantify the effects of clinical Johne's disease on the performance of Romney, Merino and Merino x Romney-cross ewes. METHODS: The performance of ewes was compared using eight birth cohorts (1971-1978). Merino and Merino-cross genotypes included New Zealand Merino and Australian Superfine Merino sources. Intensive monitoring of Johne's disease was undertaken over the production years 1975-1982. Positive diagnostic evidence of Johne's disease was established post mortem from lesions of granulomatous enteritis associated with high numbers of acid-fast bacilli. Over years, data on a total of 2,341 Romney ewes and 1,292 Merino and Merino x Romney-cross ewes were recorded, consisting of annual records of liveweight (LWT), greasy fleece weight (FWT), number of lambs born per ewe per year (NLB), and lifetime productivity of ewes. RESULTS: A total of 82 (3.5%) Romney ewes and 62 (4.8%) Merino and Merino x Romney-cross ewes were diagnosed with clinical Johne's disease over the 8-year monitoring period, equivalent to 0.9% and 1.2% annual cases for these breeds, respectively, of the ewes present at mating. The percentage of clinical cases (p<0.04) and the age at death from Johne's disease (p<0.02) were lower for Romneys than for Superfine Merinos. The mean age of death from Johne's disease was 3.41 (standard error (SE) 0.06) years, lower than the mean disposal age from the flock of 5.03 (SE 0.02) years for clinically normal ewes (p<0.001). In their final year of production, ewes with clinical Johne's disease had lower LWT by 5.3 kg (10.5% of the mean; p<0.001), lower annual FWT by 0.54 (SE 0.10) kg (14.2%; p<0.001), fewer NLB by 0.15 (SE 0.07) lambs (13%; p<0.05), and lower litter weaning weights by 3.6 (SE 1.3) kg (15%; p<0.01) compared with clinically normal ewes. The size of the production losses associated with Johne's disease depended on the age to which ewes survived. Considering all production years of ewes (up to 8 years), the total weight of lambs weaned by ewes with clinical Johne's disease was 30.9 (SE 3.4) kg lower (46%; p<0.001) than the total from clinically normal ewes. CONCLUSIONS: Clinical Johne's disease led to significant losses in LWT, FWT, NLB, and in the lifetime production of ewes, amounting overall to a 46% reduction in productivity (p<0.001). CLINICAL RELEVANCE: Productivity losses from clinical cases of Johne's disease would be of considerable economic importance in flocks with a high incidence of the disease. The lack of good diagnostic tests for Johne's disease in the live animal, and the lack of active surveillance programmes, has made it difficult to establish the true prevalence of Johne's disease in sheep flocks in New Zealand, and its economic consequences.

Genotypic effects of calpain 1 and calpastatin on the tenderness of cooked M. longissimus dorsi steaks from Jersey x Limousin, Angus and Hereford-cross cattle.

Single nucleotide polymorphisms (SNPs) in the calpain 1 (CAPN1) and calpastatin (CAST) genes were studied to determine their effects on meat tenderness in Bos taurus cattle. Strip loins (M. longissimus dorsi) were removed from cattle in four resource populations after slaughter (n = 1042), aged under controlled conditions until fixed times after rigor mortis, cooked and measured using a tenderometer. Animals were genotyped for the CAPN1 SNP c.947C>G (p.Ala316Gly; AF252504) and for the CAST SNP c.2959A>G (AF159246). Frequencies of CAPN1 C alleles ranged from 23% to 68%, and CAST A alleles from 84% to 99.5%. From all data combined, the CAPN1 CC genotype (compared with the GG genotype) was associated with a 20.1 +/- 1.7% reduced average shear force at intermediate stages of ageing (P < 0.001) and with a 9.5 +/- 1.3% reduction near ultimate tenderness (P < 0.001). The heterozygote was intermediate. For CAST, corresponding values for AA compared with AG genotypes were reductions of 8.6 +/- 2.0% and 5.1 +/- 1.6% respectively (both P < 0.001), but there were too few GG genotypes for comparison. There were small interactions between the CAPN1 and CAST genotypes. For the CAPN1 and CAST genotypes combined, the maximal genotype effect in average shear force was 25.7 +/- 5.5% (P < 0.001) at intermediate stages and 15.2 +/- 4.8% near ultimate tenderness (P < 0.01).

Relationship between sporidesmin-induced liver injury and serum activity of gamma-glutamyltransferase in Romney lambs sired by facial eczema-resistant or control rams.

AIM: To test whether long-term selection for resistance to facial eczema (FE) influences the relationship between liver injury score (LIS) and serum activity of gamma-glutamyltransferase (GGT) in sporidesmin-dosed sheep. METHODS: Two groups of Romney lambs were generated for this study in 1999, out of an unselected group of ewes and sired by either selected FE-resistant (R) line (n=74 lambs) or unselected Control (C) line (n=119 lambs) rams from the Ruakura Research Centre long-term FE-selection experiment. The lambs were given a single oral dose of sporidesmin, sampled for determination of serum GGT activity 3 weeks later, and lambs that had serum GGT activity >55 IU/l (reactors) were humanely killed and assessed for LIS post mortem, 6 weeks after dosing. A second round of dosing was applied to the nonreactors, followed as above by analysis of serum GGT activity and assessment of LIS post mortem (both reactors and nonreactors). RESULTS: There was a significant linear relationship between LIS and logeGGT, which did not differ between the 2 sire lines (LIS= -2.96 (SE 0.38) + 0.89 (SE 0.07) x loge GGT, R2=0.54, p<0.001). CONCLUSIONS: Serum GGT is a valid indicator of LIS in lambs by sires selected for different levels of susceptibility to FE. The logeGGT-LIS relationship has not changed as a result of genetic selection for resistance to FE.

Clindamycin therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

Although penicillin resistance among Streptococcus pneumoniae strains is increasing in many areas, resistance to clindamycin remains low. In our well-characterized rabbit meningitis model, we conducted experiments to evaluate the bacteriologic efficacy of clindamycin after a penicillin- and cephalosporin-resistant S. pneumoniae strain was intracisternally inoculated. Animals received a loading intravenous dose of 30 mg of clindamycin per kg of body weight and then two doses of 20 mg/kg given 5 h apart. In addition to clindamycin, some animals received dexamethasone (DXM) with or without ceftriaxone. The concentrations of clindamycin in cerebrospinal fluid were from 8.9 to 12.8% of the concomitant concentrations in serum and were unaffected by DXM administration. Mean changes in CFU (log10 per milliliter) at 10 and 24 h were -3.7 and -6.1, respectively, for clindamycin-treated rabbits, -3.6 and -6.3 for clindamycin-DXM-treated rabbits, -3.9 and -5.8, respectively, for clindamycin-ceftriaxone-treated rabbits, and -5.0 and -6.7, respectively, for clindamycin-ceftriaxone-DXM-treated rabbits. By 24 h all but one of the cultures of cerebrospinal fluid (that from a clindamycin-DXM-treated rabbit) were sterile. Because of the potential risk for clindamycin-treated rabbits to develop macrolide-lincosamide resistance, we attempted, unsuccessfully, to induce clindamycin resistance in vitro in two S. pneumoniae strains. Although clindamycin therapy might be effective in selected patients with multiple-drug-resistant pneumococcal meningitis who have failed conventional treatments, clinical experience is necessary before it can be recommended.

Evaluation of CP-99,219, a new fluoroquinolone, for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.

CP-99,219 is a new fluoroquinolone that has excellent activity against gram-positive organisms including penicillin- and cephalosporin-resistant Streptococcus pneumoniae strains. In our well-established rabbit model of meningitis, we conducted experiments to determine the concentrations of CP-99,219 in cerebrospinal fluid (CSF) after intravenous administration and its ability to eradicate two penicillin-resistant pneumococcal isolates. The peak and trough concentrations of CP-99,219 in the CSF were from 19 to 25% of the concentrations simultaneously obtained in serum and were unaffected by concomitant dexamethasone administration. Compared with untreated (control) animals, three doses of CP-99,219 given 5 h apart significantly reduced the bacterial count in CSF by 5 to 6 log10 CFU at 10 h. Although 47% of the dexamethasone-treated animals and 18% of those not given the steroid had positive cultures at 24 h (14 h after administration of the last antibiotic dose), the mean bacterial counts did not change from those observed at 10 h. Additionally, only results for animals infected with one of the two pneumococcal strains appeared to be affected by concomitant dexamethasone therapy.