Causes of mortality of kiwi (Apteryx spp.) in New Zealand: a retrospective analysis of post-mortem records, 2010-2020.

AIMS: To examine and assess causes of mortality of kiwi (Apteryx spp.) submitted to Massey University between 2010 and 2020 across the five recognised species according to location, age group and captivity status in New Zealand. METHODS: Post-mortem reports were obtained from the Massey University/Te Kunenga ki Purehuroa School of Veterinary Science/Wildbase Pathology Register. Inclusion criteria were all species of kiwi with a date of post-mortem examination between August 2010 and August 2020. Data from each report was exported, categorised and compared using Microsoft Excel. RESULTS: Of a total of 1,005 post-mortem reports, there were 766 North Island brown kiwi (NIBK; A. mantelli), 83 tokoeka (A. australis), 73 rowi (A. rowi), 49 great spotted kiwi (A. haastii), and 34 little spotted kiwi (A. owenii). This comprised 19 eggs/embryos, 125 neonatal, 473 juvenile, 153 subadult, and 235 adult kiwi. There were 615 kiwi from wild populations, 148 from sanctuary populations, 238 from captivity, and four from unspecified locations. The leading cause of death was trauma, affecting 322 (32.0 (95% CI = 29.2-35.0)%) kiwi including 289 (37.3 (95% CI = 26.0-31.7)%) NIBK. Nearly half of these died from predation by mustelids, with losses recorded from neonates to adults and clustered in the central to southern North Island. Predation by dogs was the second most common cause of death, killing 84 (8.4 (95% CI = 6.7-10.2)%) kiwi, of which 65.5% came from the northern districts of the North Island. Non-infectious disease killed 214 (21 (95% CI = 18.8-24.0)%) kiwi, and included developmental deformities, gastrointestinal foreign bodies and predator trap injuries. Infectious disease killed 181 (18.0 (95% CI = 15.7-20.5)%) kiwi and the proportion decreased with age, with common diagnoses including coccidiosis, bacterial septicaemia, avian malaria, and fungal respiratory disease. Starvation affected 42 (4.2 (95% CI = 3.0-5.6)%) kiwi, comprised of mainly neonatal or juvenile individuals from wild or sanctuary populations, with a higher percentage seen in tokoeka (11/83; 13.3%) compared to other species (min 0%, max 5.9%). The cause of death was undetermined in 246 (24.5 (95% CI = 21.8-27.3)%) cases, which was most often due to poor preservation of remains. This included 33/73 (46%) rowi and 32/83 (39%) tokoeka, and affected mainly birds from sanctuary and wild populations. CONCLUSIONS: This study enhances our understanding of causes of mortality in captive, wild and sanctuary populations of all kiwi species and age groups within contemporary New Zealand.

Vaccination practices for Leptospira spp. on New Zealand dairy farms.

AIMS: To describe leptospiral vaccination practices in dairy herds in New Zealand and evaluate conformity with best practice guidelines issued by the New Zealand Veterinary Association using data from a questionnaire administered by participating veterinary practices. METHODS: A cross-sectional study of 200 randomly selected dairy farms stratified by herd size and region throughout New Zealand was conducted from January to April 2016 to investigate leptospiral vaccination practices in dairy herds in New Zealand. Using a pre-tested questionnaire administered during a face-to-face interview, vaccination practice details such as vaccine types, time, and age of vaccination and whether vaccines were administered by veterinary or farm staff, were collected. RESULTS: Leptospiral vaccination programmes had been implemented on 199/200 (99.5 (95% CI = 97.2-99.9)%) farms, and on 178 (89.4%) of those, programmes had been running for ≥5 years. Most farmers used bivalent vaccines containing antigens for leptospiral serovars Pomona and Hardjo (144/179 (80.4%) in calves, 112/167 (60.7%) in heifers, and 112/163 (68.7%) in cows), rather than trivalent vaccines which also include antigens for L. interrogans serovar Copenhageni. In total, 123/200 (61.5%) of farmers purchased only vaccinated animals but 51/199 (25.6%) were unsure of the vaccination status of purchased cattle. Sixty-one percent (105/172) of farmers had other livestock on their farms and of them, 78/186 (42%) vaccinated some or all for Leptospira spp. Leptospiral vaccines were administered always or sometimes with other animal remedies on 30/190 (15.8%) and 91/190 (47.9%) of farms, respectively. Most farmers had not made changes to their vaccination programme in the previous 5 years. Timing of first vaccination of calves ranged from 2 weeks to 10 months of age, with 112/189 (59.3%) vaccinating by 4 months of age. Approximately half of the farms followed the best practice guideline for the timing of vaccinations for calves (high-risk farms; 67/162; 41.4%) heifers (72/165, 43.6%), and cows (171/184; 92.9%). CONCLUSIONS: The results of this survey suggest that there is almost universal adoption of leptospiral vaccination for dairy cattle in New Zealand. However, there remain areas for improvement regarding the proportion of farmers following best practice guidelines and refinement of vaccination programmes, particularly with respect to timing of vaccination in calves.

On-farm risk factors associated with Leptospira shedding in New Zealand dairy cattle.

This study aimed to evaluate risk factors associated with shedding of pathogenic Leptospira species in urine at animal and herd levels. In total, 200 dairy farms were randomly selected from the DairyNZ database. Urine samples were taken from 20 lactating, clinically normal cows in each herd between January and April 2016 and tested by real-time polymerase chain reaction (PCR) using gyrB as the target gene. Overall, 26.5% of 200 farms had at least one PCR positive cow and 2.4% of 4000 cows were shedding Leptospira in the urine. Using a questionnaire, information about risk factors at cow and farm level was collected via face-to-face interviews with farm owners and managers. Animals on all but one farm had been vaccinated against Hardjo and Pomona and cows on 54 of 200 (27%) farms had also been vaccinated against Copenhageni in at least one age group (calves, heifers and cows). Associations found to be statistically significant in univariate analysis (at P < 0.2) were assessed by multivariable logistic regression. Factors associated with shedding included cattle age (Odds ratio (OR) 0.82, 95% CI 0.71-0.95), keeping sheep (OR 5.57, 95% confidence interval (CI) 1.46-21.25) or dogs (OR 1.45, 95% CI 1.07-1.97) and managing milking cows in a single as opposed to multiple groups (OR 0.45, 95% CI 0.20-0.99). We conclude that younger cattle were more likely to be shedding Leptospira than older cattle and that the presence of sheep and dogs was associated with an increased risk of shedding in cows. Larger herds were at higher risk of having Leptospira shedders. However, none of the environmental risk factors that were assessed (e.g. access to standing water, drinking-water source), or wildlife abundance on-farm, or pasture were associated with shedding, possibly due to low statistical power, given the low overall shedding rate.

Emerging Leptospira strain poses public health risk for dairy farmers in New Zealand.

Leptospira infection in dairy cattle and leptospirosis in dairy farm workers were common in New Zealand prior to the introduction of dairy cattle vaccination in the 1980s. Despite widespread vaccination within the dairy industry, the long-term effectiveness of vaccination and current Leptospira exposure status remained unknown. A cross-sectional study was conducted from January-April 2016 to investigate the prevalence of pathogenic Leptospira spp. DNA in urine at cow and herd level, and its relationship to five Leptospira serovars known to be endemic. Two hundred dairy farms were randomly selected from the national database. Twenty paired blood and urine samples were collected on each farm from adult cows (n = 4000). Sera were tested using the Microscopic Agglutination Test against serovars Hardjobovis (termed Hardjo), Pomona, Copenhageni, Ballum and Tarassovi with titres ≥48 being considered positive. Urine was tested using quantitative real-time PCR (qPCR) that amplifies the gryB gene. All but one herd had been vaccinated with a bivalent Hardjo/Pomona or trivalent vaccine incorporating Copenhageni. In total, 2.4% of cows were urine qPCR positive and 27% of farms had at least one urine qPCR positive cow. Overall 63% of cows were seropositive to one or more serovars: 44% for Hardjo, 28% for Pomona, 15% for Copenhageni (in vaccinated herds), and for unvaccinated cows: 1% for Copenhageni, and 3% for Ballum and 17% for Tarassovi. Of the 94 qPCR urine-positive cows, 51 were seropositive to Tarassovi, 3 to Ballum, 3 to Copenhageni, 24 to Hardjo, and 17 to Pomona, the latter two presumably reflecting vaccination titres. A strong association was found between shedding and serology for Tarassovi. While there was no evidence that current vaccination programmes were ineffective in protecting against their target serovars, serovar Tarassovi has apparently emerged in NZ dairy cattle. As Tarassovi is currently not included in vaccines and is prevalent in notified leptospirosis cases in dairy workers, we concluded that this serovar poses a public health risk.

Thyroid incidentalomas on 18FDG-PET/CT: a metabolico-pathological correlation.

BACKGROUND: Thyroid incidentaloma is defined as an unsuspected thyroid lesion found on imaging study or while performing a surgery non-related to the thyroid gland. Most recent scientific literature tends to demonstrate a detection rate of 0.1-4.3% for incidental findings of thyroid focal uptake identified by 18F-fluorodeoxyglugose Positron Emission Tomography with computed tomography (18FDG-PET/CT) initially prescribed for nonthyroid disease. From 10.3 to 80.0% of patients who underwent further evaluation are diagnosed with malignant lesions. Our first objective is to determine the risk of malignancy confined in thyroid incidentalomas(IT) detected on 18FDG-PET/CT in patients treated in a tertiary care center (Centre Hospitalier Universitaire de Sherbrooke). Second, we want to identify a cut-off value for SUVmax in order to distinguish benign from malignant IT. Third, we look for predictive criterion that can be outlined to help in their management. METHODS: We retrospectively reviewed 40 914 charts of patients who had a 18FDG-PET/CT done in a tertiary center from 2004 to 2014. For each patient where a thyroid incidentaloma has been identified, Maximum Standardized Uptake Value (SUVmax), ultrasound report, cytology and histopathological results as well as oncologic outcomes were compiled and analyzed. RESULTS: In this study, the incidence for thyroid incidentaloma detected with 18FDG-PET/CT is 0.74%. The rate of malignancy present in IT is 8.2% based on histopathological results. Of the patients who underwent surgery, thyroid malignancy was identified in 54.3% of them. Cytoponction showed a strong correlation with final histopathological results (p = 0.009). CONCLUSION: Thyroid incidentalomas detected with 18FDG-PET/CT are relatively infrequent, but the potential risk of malignancy remains elevated. Fine needle aspiration biopsy is the investigation of choice to rule out a malignant incidentaloma when there is no other element in the clinical portrait to preclude such additional work up.

Factors associated with fetal losses in ewe lambs on a New Zealand sheep farm.

CASE HISTORY: As part of a production study of ewe lambs on a large farm in the Waikato region of New Zealand in 2011, pregnancy diagnosis was undertaken twice by trans-abdominal ultrasonography at 68-103 and 97-132 days of gestation. At the second pregnancy diagnosis 257/3,790 (6.8%) ewe lambs had evidence of non-viable fetuses or absence of a pregnancy that was present at the previous pregnancy diagnosis (fetal loss). LABORATORY FINDINGS: Serum antibody titres for Leptospira interrogans serovar Pomona appeared generally higher in 10 ewe lambs with fetal loss compared with 10 that were still pregnant. Histopathological investigation was not able to confirm that fetal loss was associated with leptospial infection. EPIDEMIOLOGICAL INVESTIGATION: In the 2012-born cohort of ewe lambs 443 were vaccinated with a bivalent leptospirosis vaccine and 882 unvaccinated. Serum was collected from 124 non-vaccinated ewe lambs between January and December 2013 for measurement of antibodies to Leptospira serovar Pomona and L. borgpetersenii serovar Hardjo-bovis using a microscopic agglutination test (MAT). Less than 5% of these ewe lambs were seropositive until May, but by August 85% and 48% of animals were seropositive to Leptospira serovars Hardjo-bovis and Pomona, respectively. Fetal loss in non-vaccinated ewe lambs was 78/882 (9%) compared with 23/443 (5%) in vaccinated ewe lambs. Combined data from the 2011- and 2012-born ewe lambs (n=5,115) were analysed using a logistic regression model and fetal loss as the dependent variable. In the final model fetal loss was associated with pre-mating bodyweight (p=0.003), weight change from pre-mating to initial pregnancy diagnosis (p<0.001), year born and leptospirosis vaccination status (p=0.013). Amongst the serologically monitored ewe lambs, there were associations between fetal loss and being seropositive to Leptospira serovar Pomona using titre cut-points of 1:48 and 1:768 (p<0.001). CLINICAL RELEVANCE: Low pre-mating weight and/or low weight gain from mating to pregnancy diagnosis was associated with increased fetal loss, emphasising the importance of ewe lambs achieving target pre-mating weights and liveweight gains during pregnancy. Infection with Leptospira serovar Pomona was associated with fetal loss in the 2012-born cohort and the possibility of infection with this serovar should be considered when investigating cases of fetal loss.

Serological patterns, antibody half-life and shedding in urine of Leptospira spp. in naturally exposed sheep.

AIMS: To determine within-farm prevalence, longitudinal pattern of exposure measured by serology, antibody titre longevity and point prevalence of shedding in urine of Leptospira borgpetersenii serovar Hardjo and L. interrogans serovar Pomona in naturally infected sheep on a sample of commercial farms in New Zealand. METHODS: On eight commercial sheep farms, between September 2011 and January 2014, blood samples were collected from 115-217 ewe lambs on each farm, at intervals of 2-11 months. They were analysed by microscopic agglutination test (MAT) for antibodies to L. borgpetersenii serovar Hardjo and L. interrogans serovar Pomona, using a titre cut-point of 48. Urine from 98 animals was tested by quantitative PCR (qPCR). The half-life of antibodies was estimated in 185 sheep for serovar Hardjo and 21 for Pomona, and the seroprevalence and mean titre of animals lost to follow-up was compared with those remaining in the study. RESULTS: Within-flock seroprevalence for serovar Hardjo reached a maximum at 17-22 months of age, ranging from 79 to 100%. Seroprevalence for serovar Pomona rose above 10% on three farms and increased to 21-54% by 4-14 months. Seroconversions occurred mainly from late autumn to early summer at 7-15 months of age. Seroprevalences ranging from 3 to 76% for serovar Hardjo and 0.5 to 15% for serovar Pomona were observed up to 3 months of age, likely due to maternally derived immunity. The half-life of antibody in response to infection was estimated to be 6.7 (95% CI=5.8-7.9) months for serovar Hardjo and 6.3 (95% CI=4.8-9.0) months for Pomona. The prevalence of sheep with urine positive for leptospires on qPCR on each farm ranged from 11 to 88%. All but one of the qPCR-positive animals were seropositive for serovar Hardjo. On two farms where Pomona exposure was observed, animals that were lost to follow-up had a higher geometric mean titre for serovar Pomona than those remaining in the study. CONCLUSIONS: This study demonstrated seasonal exposure from autumn to early summer in young sheep, a wide range of within-flock serological and shedding prevalence, and gives an estimation of the half-life of MAT titres in sheep. More extensive data are needed to fully understand the epidemiology of leptospirosis in sheep flocks across New Zealand and, along with economic analysis, to justify and design cost-effective and efficient control measures to protect human and animal health.

[Community- and non-community-acquired bacteremia: correlation between empiric antimicrobial therapy and susceptibility of micro-organisms isolated during 2007 in the Ile-de-France microbiologists network]. / Anti-infectieux empiriques dans les 24-48 premières heures des bactériémies des patients hospitalisés dans les hôpitaux du groupe des microbiologistes d'Ile-de-France en 2007.

AIM OF THE STUDY: To estimate the percentage of empirical treatments adapted in the bloodstream infections of community and not community origin and to determine the main circumstances in which this initial treatment is not adapted. PATIENTS AND METHODS: Surveillance of bloodstream infections from the laboratories of microbiology of the eight hospitals of the Ile-de-France network, during year 2007. The study concerned the patients hospitalised in medicine, surgery, obstetrics, intensive care, following care and rehabilitation, day hospitalisation, hospitalisation at home, who presented one or several episodes of bloodstream infections. RESULTS: During year 2007, 2013 bloodstream infections were analysed. Only 63.9% of bloodstream infections had an adapted initial antibiotic treatment. Among this proportion of bloodstream infections, an adapted empirical treatment concerned mainly the community episodes, the urinary tract, the pulmonary tract, or maternal-foetal episodes and the maternity ward and pediatrics. The percentage of adapted treatments was superior in the bloodstream infections where were isolated an Enterobacteriaceae, Streptococcus pneumoniae or other streptococci. On the contrary, only a quarter of bloodstream infections due to an Enterobacteriaceae producing BLSE or to a MRSA had received an adapted empirical treatment. CONCLUSION: Only two-thirds of the patients developing a bloodstream infection received an adapted initial antibiotic treatment. This proportion was even lower when it was not about a community origin, in spite of the frequent administration of several anti-infectious molecules or with wide spectrum.

Relationship between capsular type, penicillin susceptibility, and virulence of human Streptococcus pneumoniae isolates in mice.

We examined the relationship between penicillin susceptibility, peritoneal virulence in Swiss mice, and capsular type in a selection of 122 clinical Streptococcus pneumoniae isolates belonging to 24 serotypes. Regardless of the serotype, all 32 virulent strains were susceptible to penicillin, and all 41 strains with diminished susceptibility or resistance to penicillin were avirulent. The remaining 49 strains were both susceptible to penicillin and avirulent, irrespective of the serotype. On the basis of their capsular type and pathogenic behavior, strains fell into one of four groups. In the group consisting of serotypes 1, 3, and 4 (n = 16), strains were predominantly virulent (81.3%), and all were penicillin susceptible. In the serotype 6 group (n = 32), the frequency of virulence was significantly lower (34.4 versus 81.3%, P = 0.002), and strains were predominantly penicillin susceptible (71.9%). In the group composed of serotypes 9, 14, 19, and 23 (n = 50), all strains were avirulent, and 56% had decreased susceptibility (n = 12) or resistance to (n = 16) penicillin. The fourth group was heterogenous, as it pooled 24 strains of 15 different serotypes; in this group the frequency of virulence was 33.3%, and strains were predominantly penicillin susceptible (83.3%). These data point to a complex relationship between penicillin susceptibility and virulence in mice but do not entirely separate these characteristics from the role of the capsular type. The possibility that the mechanisms conferring penicillin resistance are related to those leading to a loss of virulence is supported by these findings.

Pharmacodynamic activities of ciprofloxacin and sparfloxacin in a murine pneumococcal pneumonia model: relevance for drug efficacy.

We looked for associations between pharmacokinetic (Pk) and pharmacodynamic (Pd) parameters of ciprofloxacin (CPFX) and sparfloxacin (SPFX) and the in vivo efficacy of these antimicrobials in an immunocompetent mouse model of severe Streptococcus pneumoniae pneumonia. Bacterial killing curves recorded in the lungs during the 24 h after single subcutaneous injections of the fluoroquinolones (FQs) in doses ranging from 6.25 to 200 mg/kg were compared with mean Pk/Pd parameters in the serum of the same mice. The impact of the dosing interval on the antimicrobial dose response was evaluated based on the survival of mice treated for 3 days with CPFX (25-200 mg/kg) or SPFX (6.25-50 mg/kg) administered at various intervals from 3 to 24 h. Bacterial killing curves showed that the maximal bacterial decrease achieved in the lungs was correlated, similarly for both FQs, with the area under the curve (AUC) above the minimal inhibitory concentration (MIC) (overall correlation: r = 0.968, P < 10(-4)). CPX attained higher maximal bactericidal effect values, a steeper killing slope and a shorter time to maximal bactericidal effect in comparison with SPX for the highest doses tested. The lower MIC of SPFX compared with CPFX (0.25 vs. 0.75 microgram/ml) and its higher AUC/dose ratio (resulting from a lower serum peak but a longer half-life) translated into a greater area under the bactericidal curve. In the dose fractionation experiments, the Pk/Pd parameter most closely correlated with the survival rate for both FQs was the daily AUC/MIC ratio (r = 0.976, P < 10(-4)). When the AUC/MIC ratio was greater than 160, the probability of a clinical cure was 100%, independently of the dosage schedule.

Pasteurella caballi infection following a horse bite.

The isolation of Pasteurella caballi from an horse-bite wound in a 56-year-old man is reported. Biochemical characteristics are described and compared with the other species representing the genus Pasteurella. This strain probably represents the first human isolate of P. caballi in France.

Correlation between in vitro and in vivo activity of amoxicillin against Streptococcus pneumoniae in a murine pneumonia model.

We studied the relationship between in vitro bacteriological parameters [minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and killing rate, defined as the reduction in the inoculum within 1, 3 or 6 hr] and in vivo activity of amoxicillin against 12 strains of Streptococcus pneumoniae, with penicillin MICs of < 0.01 to 16 micrograms/ml, in a cyclophosphamide-induced neutropenic murine pneumonia model. Dose-response curves were determined for amoxicillin against each strain, and three quantitative parameters of in vivo amoxicillin activity were defined, i.e., maximal attainable antimicrobial effect attributable to the drug [i.e., reduction in log colony-forming units (CFU) per lung, compared with untreated controls], dose required to reach 50% of maximal effect and dose required to achieve a reduction of 1 log CFU/lung. We demonstrated a highly significant correlation between the dose required to reach 50% of maximal effect and MIC (Spearman r = 0.98, P < .0001) or MBC (Spearman r = 0.95, P < .0001) for amoxicillin against strains of S. pneumoniae with a wide range of amoxicillin MICs (0.01-8 micrograms/ml). Significant correlations between the dose required to achieve a reduction of 1 log CFU/lung and MIC (Spearman r = 0.98, P < .0001) or MBC (Spearman r = 0.95, P < .0001) were also observed. In contrast, there were no significant correlations between the maximal attainable antimicrobial effect attributable to the drug and MIC, MBC or killing rate or between killing rate and the dose required to reach 50% of maximal effect or the dose required to achieve a reduction of 1 log CFU/lung. We conclude that in vitro susceptibility test results (MICs and MBCs) correlated well with in vivo amoxicillin activity against pneumococcal strains, including highly penicillin-resistant strains, in this animal model. Furthermore, these data suggest that the estimated MIC breakpoints for amoxicillin against S. pneumoniae would be 2 micrograms/ml for intermediate-resistant and 4 micrograms/ml for resistant, although this remains to be confirmed in clinical studies.

Western blot analysis of antibody response to pneumococcal protein antigens in a murine model of pneumonia.

To detect new antigen candidates for serological tests, we studied the antibody response to pneumococcal protein antigens in mice infected intratracheally with various Streptococcus pneumoniae strains. Sera were tested by Western blotting against whole-cell protein extracts. Mice developed a detectable immunoglobulin G-type response against a small number of polypeptides. The antibody response was strain dependent: sera from individuals infected with the same strain gave similar banding patterns on immunoblots. The banding patterns varied with the strain used for infection. However, a band at 36 to 38 kDa was recognized by all reactive sera. This band appeared to correspond to a polypeptide that was antigenically well conserved among the different S. pneumoniae serotypes. An antibody response to this antigen developed in mice irrespective of the capsular type, the virulence, and the susceptibility to penicillin G of the infecting strain. Thus, this 36- to 38-kDa protein antigen may be of value for the development of a serological test for humans.

Synergy between amoxicillin and gentamicin in combination against a highly penicillin-resistant and -tolerant strain of Streptococcus pneumoniae in a mouse pneumonia model.

In vivo synergy with beta-lactam antibiotics and aminoglycosides has been studied only with penicillin-susceptible Streptococcus pneumoniae strains. We evaluated the interaction between amoxicillin (AMX) and gentamicin (GEN) on the basis of in vitro checkerboard and time-kill curves and of findings in a mouse model of acute bacteremic pneumonia due to a highly penicillin-resistant and -tolerant S. pneumoniae strain of serotype 19 (penicillin and AMX MICs of 4 micrograms/ml; gentamicin MIC of 16 micrograms/ml). Checkerboard results at 18 h of incubation showed indifference. With regard to AMX alone, in vitro time-kill curves demonstrated synergy between AMX (1 microgram/ml) and GEN (16 micrograms/ml) at 5 and 8 h of incubation and for AMX (16 micrograms/ml) in combination with GEN (16 micrograms/ml) at 3, 5, and 8 h of incubation. In leukopenic mice, pulmonary killing curves after a single drug injection demonstrated that AMX (100 mg/kg of body weight) with GEN (16 mg/kg) was more effective than AMX alone (P = 10(-4). With repeated-dose treatment, a synergy was apparent at 8 h after four injections with AMX (100 mg/kg) in combination with GEN (8 or 16 mg/kg) (P < or = 0.05). The cumulative survival rate with AMX (100 mg/kg) every 8 h, combined with GEN (4 or 8 mg/kg) every 8, 12, or 24 h, was better than with AMX alone. Combined use of AMX and GEN may be a valuable therapeutic alternative for pneumococcal pneumonia due to highly penicillin-resistant S. pneumoniae strains.

Amoxicillin dose-effect relationship with Streptococcus pneumoniae in a mouse pneumonia model and roles of in vitro penicillin susceptibilities, autolysis, and tolerance properties of the strains.

We used a mouse model of pneumococcal pneumonia to assess the bactericidal effect of increasing doses of amoxicillin (AMX) against clinical strains with various susceptibilities to penicillin. Twelve strains that exhibited similar virulence in mice were selected. Three were penicillin susceptible (PS) (penicillin and AMX MICs = 0.01 to 0.03 microgram/ml), three were intermediately resistant (PIR) (penicillin and AMX MICs = 0.5 to 1 microgram/ml), and six were penicillin resistant (PR) (penicillin and AMX MICs = 1 to 8 micrograms/ml). Leukopenic Swiss mice were infected intratracheally with 10(7) CFU of each strain. Treatment was initiated 3 h after infection and consisted of a single subcutaneous injection of AMX at doses ranging from 2.5 to 10 mg/kg (PS strains), 5 to 100 (PIR strains), and 25 to 3,000 (PR strains). Bacterial killing kinetics were recorded in the lungs over 9 h. The maximal log CFU reduction (Emax) was observed 3 h postinjection. The relation between Emax and log10(dose/MIC) showed two populations. With seven strains (the three PS, the three PIR, and one of the six PR [MICs, penicillin/AMX = 4/1]) a good correlation was observed between Emax and log10(dose/MIC) (r = 0.772; P < 0.02). A bactericidal effect equal to 3.5 log10 CFU was observed at a log10(dose/MIC) = 2. At this ratio, with the five other PR strains, Emax varied from 0.4 to 1.6 log10 CFU. In brain heart infusion medium containing AMX at 50 times the relevant MIC, these five PR strains were tolerant in vitro. Treatment failure with AMX was found in vivo, with tolerant, highly resistant strains.

Diagnosis of tuberculosis by Amplicor Mycobacterium tuberculosis test: a multicenter study.

The Amplicor Mycobacterium tuberculosis test is a new PCR assay for the direct detection of Mycobacterium tuberculosis from clinical samples. A multicenter study that included six laboratories was done to evaluate the Amplicor test in comparison with direct microscopy and culture (solid or radiometric media), and the culture method was used as the "gold standard." A total of 2,073 specimens, i.e., 1,749 respiratory specimens and 324 other specimens, were tested. A total of 184 cultures yielded M. tuberculosis. Of these 184 cultures, 77 (42%) were smear negative and 23 (12.5%) concerned extrapulmonary specimens. The sensitivity of the Amplicor test for all of the specimens and for extrapulmonary, smear-positive, and smear-negative specimens was 86, 83, 94.5, and 74%, respectively. The sensitivity of direct microscopy in comparison with that of culture was 58%. A total of 95% of patients with culture-proven tuberculosis were diagnosed by the Amplicor test, whereas direct microscopy detected mycobacteria in only 72% of these patients. The Amplicor test exhibited a high degree of specificity (98%). The assay was very rapid and easy to perform.

[Mycobacterium gordonae infections in human immunodeficiency virus infection]. / Infections à Mycobacterium gordonae au cours de l'infection par le virus de l'immunodéficience humaine.

OBJECTIVES: Non-tuberculous mycobacteria infections are frequent in patients infected with the human immunodeficiency virus (HIV). Mycobacterium avium intracellulare is the most frequent organism isolated but several other mycobacteria are also seen. Mycobacterium gordonae is a saprophytic mycobacteria which is rarely pathogenic. It was observed in 9% (7 patients) of the mycobacterial infections observed in our unit over a period of 3 years. METHODS: In order to determine whether M. gordonae plays a pathogenic role in HIV-infected patients, we re-evaluated the 7 clinical files of patients with M. gordonae infection. The findings were compared with data in the literature. RESULTS: All seven of our patients had a poor general health status with fever and pulmonary infection. The chest X-ray was abnormal in 5 patients. M. gordonae was isolated from blood cultures in 2 patients and from sputum or gastric contents in 5. Outcome was favourable using anti-tuberculosis combinations. CONCLUSION: A pathogenic role for M. gordonae cannot be excluded in HIV-infected patients. However, since this mycobacterium is an ubiquitous organism, diagnosis should be based on a typical clinical presentation and certain laboratory identification from appropriate samples.

[Tuberculosis in Africans hospitalized in Paris. Impact of infection by the human immunodeficiency virus]. / Tuberculose chez des Africains hospitalisés à Paris. Impact de l'infection par le virus de l'immunodéficience humaine.

OBJECTIVES: Human immunodeficiency virus (HIV) infection has greatly modified the epidemiology and clinical course of tuberculosis. The aim of this study was to analyze the characteristics of tuberculosis in African patients hospitalized in Paris by comparing clinical features in patients with and without HIV infection. METHODS: Hospital records of 71 patients from Africa hospitalized between 1989 and 1992 in Paris with a certain or probable diagnosis of tuberculosis were studied retrospectively. RESULTS: There were 30 patients (42%) with HIV infection. In 12 of them (40%) HIV positivity was discovered at diagnosis of tuberculosis. Age, sex, and duration of residence in France before diagnosis were similar between HIV+ and HIV- patients. Pulmonary tuberculosis was found in 23 patients and extrapulmonary forms (mainly lymph node involvement) were seen in 34; both in 14 patients. There was no difference in localization between HIV+ and HIV- patients except for disseminated tuberculosis which was more frequent in HIV+ patients. Skin reactions to tuberculin were positive in 76% and 97% of the HIV- and HIV+ patients respectively (p < 0.02). Drug resistance was observed in 8 patients (6 HIV+): streptomycin (n = 6), pyrazinamide (n = 2), isoniazide (n = 2), ethambutol (n = 1) and rifampicin (n = 1). Drug therapy was successful in controlling the initial manifestations of tuberculosis in both HIV+ and HIV- patients. CONCLUSION: Extrapulmonary forms of tuberculosis, especially lymph node infection was more frequent in Africans hospitalized in Paris, whether the patients were HIV positive or negative. HIV infection was associated with disseminated tuberculosis, non-excavated pulmonary tuberculosis and undesirable side effects of antituberculosis drugs.

In vivo efficacy of a broad-spectrum cephalosporin, ceftriaxone, against penicillin-susceptible and -resistant strains of Streptococcus pneumoniae in a mouse pneumonia model.

The increasing emergence of penicillin-resistant (Pr) strains of Streptococcus pneumoniae could pose a therapeutic problem in the next few years. Ceftriaxone (CRO), a broad-spectrum cephalosporin, exhibits a smaller increase in MICs against Pr S. pneumoniae strains than amoxicillin (AMO) (usually referred as to the "gold standard" therapy for pneumococcal infections). Therefore, we compared their respective efficacies in a leukopenic Swiss mouse model of pneumococcal pneumonia. Infection was induced with two serotype 19 strains: a penicillin-susceptible (Ps) strain (MICs of < 0.01 for penicillin, 0.03 for AMO, and 0.03 for CRO) and a Pr strain (MICs of 4 for penicillin, 2 for AMO, and 0.5 for CRO). Untreated mice died within 2 or 3 days. Against the Ps strain, the minimal protective dose (two subcutaneous injections at 12-h intervals for 3 days) for both CRO and AMO was 5 mg/kg of body weight (87% survivors). Ten-fold-increased doses of CRO (50 mg/kg) gave similar protection (75% survivors) against the Pr strain, whereas 20- and 40-fold-increased doses of AMO protected 0 and 34% of the animals, respectively, against the Ps strain. CRO had a marked and prolonged antibacterial effect in the lungs (2.7-log-unit reduction of CFU in 24 h after a single 50-mg/kg injection) against the Pr strain in comparison with AMO. A standard dosage of 50 mg of CRO per kg in mice resulted in peak levels in serum and protein binding comparable to those observed with 1 g given intravenously in humans. This dosage remained effective against a highly Pr S. pneumoniae strain in this model. The microbiological activity and pharmacodynamic and pharmacokinetic properties of CRO (time during which concentrations exceed the MIC for the test pathogen [delta t MIC], > or less than 8 h; and peak/MIC ratio, >90 for free active drug) accounted for its efficacy relative to AMO (50 mg/kg: delta t MIC, <2; peak/MIC ratio, <25) against the highly Pr S. pneumoniae strain used in this study.