Oral amoxicillin plus gentamicin regimens may be superior to the procaine-penicillin plus gentamicin regimens for treatment of young infants with possible serious bacterial infection when referral is not feasible: Pooled analysis from three trials in Africa and Asia.

Background: Hospital referral and admission in many- low and middle-income countries are not feasible for many young infants with sepsis/possible serious bacterial infection (PSBI). The effectiveness of simplified antibiotic regimens when referral to a hospital was not feasible has been shown before. We analysed the pooled data from the previous trials to compare the risk of poor clinical outcome for young infants with PSBI with the two regimens containing injectable procaine penicillin and gentamicin with the oral amoxicillin plus gentamicin regimen currently recommended by the World Health Organization (WHO) when referral is not feasible. Methods: Infant records from three individually randomised trials conducted in Africa and Asia were collated in a standard format. All trials enrolled young infants aged 0-59 days with any sign of PSBI (fever, hypothermia, stopped feeding well, movement only when stimulated, or severe chest indrawing). Eligible young infants whose caretakers refused hospital admission and consented were enrolled and randomised to a trial reference arm (arm A: procaine benzylpenicillin and gentamicin) or two experimental arms (arm B: oral amoxicillin and gentamicin or arm C: procaine benzylpenicillin and gentamicin initially, followed by oral amoxicillin). We compared the rate of poor clinical outcomes by day 15 (deaths till day 15, treatment failure by day 8, and relapse between day 9 and 15) in reference arm A with experimental arms and present risk differences with 95% confidence interval (CI), adjusted for trial. Results: A total of 7617 young infants, randomised to arm A, arm B, or arm C in the three trials, were included in this analysis. Most were 7-59 days old (71%) and predominately males (56%). Slightly over one-fifth of young infants had more than one sign of PSBI at the time of enrolment. Severe chest indrawing (45%), fever (43%), and feeding problems (25%) were the most common signs. Overall, those who received arm B had a lower risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -2.1%, 95% CI = -3.8%, -0.4%; P = 0.016) and intention-to-treat (risk difference = -1.8%, 95% CI = -3.5%, -0.2%; P = 0.031) analyses. Those who received arm C did not have an increased risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -1.1%, 95% CI = -2.8%, 0.6%) and intention-to-treat (risk difference = -0.8%, 95% CI = -2.5%, 0.9%) analyses. Overall, those who received arm B had a lower risk of poor clinical outcome compared to the combined arms A and C for both per-protocol (risk difference = -1.6%, 95% CI = -3.5%, -0.1%; P = 0.035) and intention-to-treat (risk difference = -1.4%, 95% CI = -2.8%, -0.1%; P = 0.049) analyses. Conclusions: Analysis of pooled individual patient-level data from three large trials in Africa and Asia showed that the WHO-recommended simplified antibiotic regimen B (oral amoxicillin and injection gentamicin) was superior to regimen A (injection procaine penicillin and injection gentamicin) and combined arms A and C (injection procaine penicillin and injection gentamicin, followed by oral amoxicillin) in terms of poor clinical outcome for the outpatient treatment of young infants with PSBI when inpatient treatment was not feasible. Registration: AFRINEST study [9] is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12610000286044. SATT Bangladesh study [10] is registered with ClinicalTrials.gov: NCT00844337. SATT Pakistan study [11] is registered at ClinicalTrials.gov: NCT01027429.

An atypical Bacillus anthracis infection in a bull-A potential occupational health hazard.

Bacillus anthracis infecting cattle is usually identified based on the typical symptom: sudden death. Bacillus anthracis causing atypical symptoms may remain undiagnosed and represent a potential occupational health hazard for, that is veterinarians and producers, butchers and tanners. In the year 2004, one case of sudden death in a dairy farm in southern Finland was diagnosed as bovine anthrax. Four years later 2008, an atypical case of anthrax was diagnosed in the same holding. The bull was taken to the Production Animal Hospital of the Faculty of Veterinary Medicine, University of Helsinki because of fever, loss of appetite and a symmetrically swollen scrotal sac. Penicillin treatment cured the fever but not the swollen scrotum. Before the intended therapeutic castration, a punctuate consisting of 10 ml fluid collected into a syringe from the scrotal sac was cultivated on blood agar at 37°C. After 24 hr, an almost pure culture of a completely non-hemolytic Bacillus cereus-like bacteria was obtained. The strain was identified as B. anthracis using Ba-specific primers by the Finnish Food Safety Authority (RUOKAVIRASTO). After the diagnosis, the bull was euthanized and destroyed, the personnel were treated with prophylactic antibiotics and the clinic was disinfected. In this particular case, treatment with water, Virkon S and lime seemed to be effective to eliminate endospores and vegetative cells since no relapses of anthrax have occurred in 10 years. This case is the last reported anthrax case in Finland.

Antibiotic treatment for newborns with congenital syphilis.

BACKGROUND: Congenital syphilis continues to be a substantial public health problem in many parts of the world. Since the first use of penicillin for the treatment of syphilis in 1943, which was a notable early success, it has remained the preferred and standard treatment including for congenital syphilis. However, the treatment of congenital syphilis is largely based on clinical experience and there is extremely limited evidence on the optimal dose or duration of administration of penicillin or the use of other antibiotics. OBJECTIVES: To assess the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable and possible congenital syphilis. SEARCH METHODS: We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 23 May 2018. We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotic treatment (any concentration, frequency, duration and route) with no intervention or any other antibiotic treatment for neonates with confirmed, highly probable or possible congenital syphilis. DATA COLLECTION AND ANALYSIS: All review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Two RCTs (191 participants) met our inclusion criteria and none of these trials was funded by the industry. One trial (22 participants) compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low-quality evidence suggested that benzathine penicillin administration may not have decreased the rate of neonatal death due to any cause (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.06 to 11.70), and showed a possible reduction into the proportion of neonates with clinical manifestations of congenital syphilis (RR 0.12, 95% CI 0.01 to 2.09). Penicillin administration increased the serological cure at the third month (RR 2.13, 95% CI 1.06 to 4.27). These results should be taken with caution, because the trial was stopped early because there were four cases with clinical congenital syphilis in the no treatment group and none in the treatment group. Interim analysis suggested this difference was significant. This study did not report neonatal death due to congenital syphilis or the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of imprecision and risk of bias.One trial (169 participants) compared benzathine penicillin versus procaine benzylpenicillin. High- and moderate-quality evidence suggested that there were probably no differences between benzathine penicillin and procaine benzylpenicillin for the outcomes: absence of clinical manifestations of congenital syphilis (RR 1.00, 95% CI 0.97 to 1.03) and serological cure (RR 1.00, 95% CI 0.97 to 1.03). There were no cases of neonatal death due congenital syphilis; all 152 babies who followed up survived. This study did not report on the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of serious risk of bias. AUTHORS' CONCLUSIONS: At present, the evidence on the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable or possible congenital syphilis is sparse, implying that we are uncertain about the estimated effect. One trial compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low-quality evidence suggested penicillin administration possibly reduce the proportion of neonates with clinical manifestations of congenital syphilis, penicillin administration increased the serological cure at the third month. These findings support the clinical use of penicillin in neonates with confirmed, highly probable or possible congenital syphilis. High- and moderate-quality evidence suggests that there are probably no differences between benzathine penicillin and procaine benzylpenicillin administration for the outcomes of absence of clinical manifestations of syphilis or serological cure.

Comparative therapeutic efficacy of Phyllanthus emblica (Amla) fruit extract and procaine penicillin in the treatment of subclinical mastitis in dairy buffaloes.

To investigate the comparative therapeutic efficacy of Phyllanthus emblica (Amla) fruit extract and procaine penicillin in the treatment of subclinical mastitis, a total of 30 subclinical mastitis positive buffaloes out of 194 lactating buffaloes were divided into 3 equal groups viz. A, B and C. Group A was treated with procaine penicillin, group B was treated with Phyllanthus emblica fruit extract and group C was served as control for 5 days respectively. The collected milk samples were subjected to the treatment trials before and after the treatment at day 0, 7th and 14th day aseptically. The evaluation parameters were bacteriological cure rate, milk pH, milk yield. The percentage cure rate of sub-clinically mastitic quarters in group A, B and C were 80.95%, 64.7% and 22.22% at day 14 respectively. The quarter based bacteriological cure rate was highest in group A (80.95%) followed by group B (64.7%) and group C (22.22%). The pH was significant (P > .05) in group A, B and C at day 0, 7 and 14. It is concluded that Phyllanthus emblica fruit extract is an inexpensive source in the treatment of subclinical mastitis in dairy buffaloes and can be used as an alternative to antibiotic therapy as for procaine penicillin.

Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

BACKGROUND: Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. METHODS: We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. FINDINGS: Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference -1·9, 95% CI -5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, -2·3 to 4·5). INTERPRETATION: Two simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital. FUNDING: The Saving Newborn Lives initiative of Save the Children, through support from the Bill & Melinda Gates, and by WHO and USAID.

Clinical Manifestations and Outcome of Syphilitic Uveitis.

PURPOSE: To analyze visual outcome, effectiveness of various modes of antibiotic treatment, and prognostic factors in patients with serologically proven syphilitic uveitis. METHODS: The clinical records of 85 patients (139 eyes) diagnosed with syphilitic uveitis between 1984 and 2013 at tertiary centers in The Netherlands were retrospectively analyzed. RESULTS: Mean age was 47 years (range, 27-73 years), 82.4% were male. HIV positivity was found in 28 (35.9%) patients; 13 were newly diagnosed. Most patients had pan (45.9%) or posterior (31.8%) uveitis. On average, logMAR visual acuity (VA) improved significantly from 0.55 at the start of syphilis treatment to 0.34 at 1 month and to 0.27 at 6 months follow-up. Most patients (86.7%) reached disease remission. No differences in efficacy between the various treatment regimens were found. A high logMAR VA at the start of syphilis treatment and a treatment delay of more than 12 weeks were prognostic for a high logMAR VA at 6 months follow-up. Chronicity was not related to any form of treatment, HIV status, or Venereal Disease Research Laboratory test outcome. CONCLUSIONS: In this large cohort of 85 patients with syphilitic uveitis, visual outcomes were favorable in the majority of cases. Visual outcome was dependent on VA at the start of syphilis treatment and treatment delay.

Symptomatic Early Congenital Syphilis: A Common but Forgotten Disease.

Congenital syphilis is a severe, disabling infection often with grave consequences seen in infants. It occurs due to the transmission of the disease from an infected mother to the unborn infant through the placenta. Congenital syphilis can involve any organ system and present with various symptoms. However, early diagnosis of congenital syphilis is difficult because more than half of the affected infants are asymptomatic, and the signs in symptomatic infants may be subtle and nonspecific. The continuing prevalence of this disease reveals the failure of control measures established for its prevention. Here we report a case of a one-month infant who presented with skin rash. The report stresses upon the importance of implementing the World Health Organization's recommendation that all pregnant women should be screened for syphilis in the first antenatal visit in the first trimester and again in the late pregnancy.

T-CELL LYMPHOCYTIC LEUKEMIA IN A FALLOW DEER (DAMA DAMA).

A 17-yr-old female fallow deer presented with ataxia, inappetence, decreased fecal output, and decreased mentation. A complete blood count demonstrated leukocytosis (24.1×10(3)/µl, n=1.16-7.38×10(3)/µl), characterized by lymphocytosis (22.89×10(3)/µl, n=0.18-3.65×10(3)/µl), anemia (packed cell volume 20%, n=29.0-55.8%), decreased red blood cell count (4.1×10(3)/µl, n=6.86-14.72×10(3)/µl), and decreased hemoglobin (7.5 g/dl, n=9.4-19.2 g/dl). Numerous mature, well-differentiated lymphocytes were noted on the blood film. Despite treatment and clinical improvement, the decision was made to euthanize the deer. Histopathology identified a monomorphic population of CD3 positive, CD79a negative small lymphocytes replacing most of the hematopoietic tissue in the bone marrow without evidence of tissue invasion. Results of viral screening were negative.

Simplified antibiotic regimens compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with clinical signs of possible serious bacterial infection when referral is not possible: a randomised, open-label, equivalence trial.

BACKGROUND: WHO recommends hospital-based treatment for young infants aged 0-59 days with clinical signs of possible serious bacterial infection, but most families in resource-poor settings cannot accept referral. We aimed to assess whether use of simplified antibiotic regimens to treat young infants with clinical signs of severe infection was as efficacious as an injectable procaine benzylpenicillin-gentamicin combination for 7 days for situations in which hospital referral was not possible. METHODS: In a multisite open-label equivalence trial in DR Congo, Kenya, and Nigeria, community health workers visited all newborn babies at home, identifying and referring unwell young infants to a study nurse. We stratified young infants with clinical signs of severe infection whose parents did not accept referral to hospital by age (0-6 days and 7-59 days), and randomly assigned each individual within these strata to receive one of the four treatment regimens. Randomisation was stratified by age group of infants. An age-stratified randomisation scheme with block size of eight was computer-generated off-site at WHO. The outcome assessor was masked. We randomly allocated infants to receive injectable procaine benzylpenicillin-gentamicin for 7 days (group A, reference group); injectable gentamicin and oral amoxicillin for 7 days (group B); injectable procaine benzylpenicillin-gentamicin for 2 days, then oral amoxicillin for 5 days (group C); or injectable gentamicin for 2 days and oral amoxicillin for 7 days (group D). Trained health professionals gave daily injections and the first dose of oral amoxicillin. Our primary outcome was treatment failure by day 8 after enrolment, defined as clinical deterioration, development of a serious adverse event (including death), no improvement by day 4, or not cured by day 8. Independent outcome assessors, who did not know the infant's treatment regimen, assessed study outcomes on days 4, 8, 11, and 15. Primary analysis was per protocol. We used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000286044. FINDINGS: In Kenya and Nigeria, we started enrolment on April 4, 2011, and we enrolled the necessary number of young infants aged 7 days or older from Oct 17, 2011, to April 30, 2012. At these sites, we continued to enrol infants younger than 7 days until March 29, 2013. In DR Congo, we started enrolment on Sept 17, 2012, and continued until June 28, 2013. We randomly assigned 3564 young infants to either group A (n=894), group B (n=884), group C (n=896), or group D (n=890). We excluded 200 randomly assigned infants, who did not fulfil the predefined criteria of adherence to treatment and adequate follow-up. In the per-protocol analysis, 828 infants were included in group A, 826 in group B, 862 in group C, and 848 in group D. 67 (8%) infants failed treatment in group A compared with 51 (6%) infants in group B (risk difference -1·9%, 95% CI -4·4 to 0·1), 65 (8%) in group C (-0·6%, -3·1 to 2·0), and 46 (5%) in group D (-2·7%, -5·1 to 0·3). Treatment failure in groups B, C, and D was within the similarity margin compared with group A. During the 15 days after random allocation, 12 (1%) infants died in group A, compared with ten (1%) infants in group B, 20 (2%) infants in group C, and 11 (1%) infants in group D. An infant in group A had a serious adverse event other than death (injection abscess). INTERPRETATION: The three simplified regimens were as effective as injectable procaine benzylpenicillin-gentamicin for 7 days on an outpatient basis in young infants with clinical signs of severe infection, without signs of critical illness, and whose caregivers did not accept referral for hospital admission. FUNDING: Bill & Melinda Gates Foundation grant to WHO.

Comminuted fracture of the accessory carpal bone removed via an arthroscopic-assisted arthrotomy.

A 16-year-old American paint horse gelding was presented for evaluation of a left forelimb lameness grade III/V. Radiographs and computed tomography revealed a comminuted fracture of the accessory carpal bone involving the entire articulation with the distal radius and the proximal aspect of the articulation with the ulnar carpal bone. Multiple fragments were present in the palmar pouch of the antebrachiocarpal joint. An arthroscopic-assisted open approach was necessary to remove all fractured fragments. Subsequently the horse was re-admitted for lameness and was treated successfully with antibiotics and long-term supportive bandaging.

Fracture comminutive de l'os du carpe accessoire enlevé à l'aide d'une arthrotomie assistée par arthroscopie. Un cheval American Paint Horse âgé de 16 ans a été présenté pour l'évaluation d'une boiterie de la jambe avant gauche de grade III/V. Les radiographies et la tomodensitométrie ont révélé une fracture comminutive de l'os du carpe accessoire touchant toute l'articulation avec le radius distal et l'aspect proximal de l'articulation avec l'os du carpe cubital. Des fragments multiples étaient présents dans la poche palmaire de l'articulation antébrachio-carpienne. Une approche ouverte assistée par arthroscopie a été nécessaire pour retirer tous les fragments fracturés. Le cheval a ensuite été réadmis pour boiterie et a été traité avec succès à l'aide d'antibiotiques et de pansements de soutien à long terme.(Traduit par Isabelle Vallières).

Successful medical management of intra-abdominal abscesses in 4 adult horses.

Four adult horses with large intra-abdominal abscesses, suspected to be complications of strangles, were treated with systemic antibiotics alone and made a full recovery. The 100% survival rate is significantly better than other reported survival rates. The median duration of treatment (35 days) was shorter than in most previous reports. This study suggests that penicillin G can be used for successful treatment of strangles associated intra-abdominal abscesses in horses.

Gestion médicale réussie d'abcès intra-abdominaux chez 4 chevaux adultes. Quatre chevaux adultes avec des abcès intra-abdominaux de grande taille, suspectés d'être des complications de la gourme, ont été traités seulement à l'aide d'antibiotiques systémiques et se sont rétablis complètement. Le taux de survie de 100 % est significativement meilleur que les autres taux de survie signalés. La durée médiane du traitement (35 jours) a été plus courte que celle indiquée dans la plupart des rapports antérieurs. Cette étude suggère que la pénicilline G peut être utilisée avec succès pour le traitement des abcès intra-abdominaux associés à la gourme chez les chevaux.(Traduit par Isabelle Vallières).

Maternal mortality in a rural Tanzanian hospital: fatal Jarisch-Herxheimer reaction in a case of relapsing fever in pregnancy.

Relapsing fever is a disease caused by one of the species of Borrelia. It is often misdiagnosed as malaria and can have fatal complications such as the Jarisch-Herxheimer reaction (JHR) after the commencement of treatment with antibiotics. A 19-year-old Tanzanian woman was admitted after a term home delivery that day. She presented with a 2 day history of fever, headache, general body malaise and vomiting. She was misdiagnosed as having severe malaria and was treated with quinine. The blood slide showed Borrelia duttoni. The patient continued treatment with procaine penicillin fortified for relapsing fever. Several hours later the woman died, probably due to JHR. This case of a patient with relapsing fever who died from a JHR stresses the importance of adequate diagnosis and treatment which should include careful monitoring, especially for the first hours after starting antibiotics.

Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: II. Cow health and performance in early lactation.

The objective of this randomized noninferiority clinical trial was to compare the effect of treatment with 3 different dry cow therapy formulations at dry-off on cow-level health and production parameters in the first 100 d in milk (DIM) in the subsequent lactation, including 305-d mature-equivalent (305 ME) milk production, linear score (LS), risk for the cow experiencing a clinical mastitis event, risk for culling or death, and risk for pregnancy by 100 DIM. A total of 1,091 cows from 6 commercial dairy herds in 4 states (California, Iowa, Minnesota, and Wisconsin) were randomly assigned at dry-off to receive treatment with 1 of 3 commercial products: Quartermaster (QT; Zoetis Animal Health, Madison, NJ), Spectramast DC (SP; Zoetis Animal Health) or ToMorrow Dry Cow (TM; Boehringer Ingelheim Vetmedica Inc., St Joseph, MO). All clinical mastitis, pregnancy, culling, and death events occurring in the first 100 DIM were recorded by farm staff using an on-farm electronic record-keeping system. Dairy Herd Improvement Association test-day records of milk production and milk component testing were retrieved electronically. Mixed linear regression analysis was used to describe the effect of treatment on 305ME milk production and LS recorded on the last Dairy Herd Improvement Association test day before 100 DIM. Cox proportional hazards regression analysis was used to describe the effect of treatment on risk for experiencing a case of clinical mastitis, risk for leaving the herd, and risk for pregnancy between calving and 100 DIM. Results showed no effect of treatment on adjusted mean 305 ME milk production (QT=11,759 kg, SP=11,574 kg, and TM=11,761 kg) or adjusted mean LS (QT=1.8, SP=1.9, and TM=1.6) on the last test day before 100 DIM. Similarly, no effect of treatment was observed on risk for a clinical mastitis event (QT=14.8%, SP=12.7%, and TM=15.0%), risk for leaving the herd (QT=7.5%, SP=9.2%, and TM=10.3%), or risk for pregnancy (QT=31.5%, SP=26.1%, and TM=26.9%) between calving and 100 DIM.