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Ruxolitinib has been approved for the treatment of adults and pediatric patients ≥12 years with steroid refractory graft-versus-host disease (GvHD). However, real-life studies are needed to confirm the results of clinical trials and further assess its efficacy in special populations. We performed a descriptive, retrospective, multi-center study of 352 adults and 42 pediatric patients treated with ruxolitinib for steroid-refractory acute or chronic GvHD. Among 119 and 233 adult patients with acute and chronic GvHD, overall response rate (ORR) was 58.8% (CR 33.6%) and 65.7% (CR 18.5%), respectively. Corticosteroids were withdrawn in 59.2% and 40.1%, and ruxolitinib in 47.2% and 34.8% in the acute and chronic groups of responders. Among 29 and 13 pediatric patients with acute and chronic GvHD, ORR was 82.7% (CR 51.7%) and 100% (CR 23%), respectively. Among responder patients, corticosteroids were withdrawn in 72.7% and 50%, and ruxolitinib in 75% and 30.7% in both groups respectively. Ruxolitinib in the real world setting, showed similar results as compared to clinical trials. Its efficacy is maintained in subsequent lines of treatment. In the pediatric population, the data are more favorable. In the long-term follow-up, corticosteroids, ruxolitinib and other inmunosuppressive drugs could be eliminated in a remarkably proportion of patients., Competing Interests: Competing interests: The study was funded by Novartis Company. VGG and GETH-TC received support from Novartis Company. The rest of the authors declare no competing financial interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

A Chlamydia trachomatis variant that contains a 377 bp deletion in the cryptic plasmid was recently reported in Sweden. This deletion includes the targets for Cobas Amplicor, Cobas TaqMan48, and Abbott m2000. We examined the proportion and characteristics of this variant in Orebro county, Sweden and developed an effective diagnostic solution. In total, 2,401 consecutive C. trachomatis culture samples and 536 PCR samples from symptomatic and asymptomatic patients and screened females were included. Culture, Cobas Amplicor, and LightMix 480HT were used for diagnosis. A mutant-specific PCR, plasmid sequencing, omp1 sequencing and multilocus sequence typing (MLST) were used to identify and characterise mutants. In total, 162 (6.7%) of the cultured samples were positive for C. trachomatis. However, 61 (38%) of those were negative when using Cobas Amplicor, and 60 of these were subsequently confirmed as the new variant. 13 of these mutant isolates were further characterised genetically, and all were of identical genotype E and the unique MLST sequence type: 21, 19, 1, 2, 1. Of all culture-positive samples, 161 of 162 were positive in the LightMix 480HT assay. The single negative sample was only weakly positive in culture, and negative in all PCRs. Of the 536 PCR samples, 37 were positive in both Cobas Amplicor and LightMix 480HT, 13 were only positive in LightMix 480HT (mutants), and two were only positive in Cobas Amplicor. Mutated C. trachomatis were prevalent in Orebro county in the period from October 2006 to February 2007, and it appeared to be a single clone. LightMix 480HT seemed sensitive, specific, and enabled high throughput diagnostics. However, rare low positive samples may be false-negative. Frequent surveillance and evaluations of diagnostic methods worldwide are crucial.

Invasive disease caused by antibiotic resistant pneumococci is a worldwide problem. All invasive pneumococcal strains in an area of south-west Sweden with 1.7 million inhabitants were collected prospectively during 1998-2001. Minimum inhibitory concentrations (MICs) were determined by E-test and correlated to serotypes and clinical characteristics. Of 827 strains, 744 (90%) were susceptible (S) to all agents tested and 83 (10%) were indeterminate (I) or resistant (R) to at least 1 agent. 22 isolates (2.7%) were I to penicillin (MIC >0.06 to < or = 1.0 mg/l), but none were R (MIC >1.0 mg/l). Numbers and proportions of decreased susceptibility against other agents tested were as follows: erythromycin R: 30 (3.6%), clindamycin R: 6 (0.7%), tetracycline R: 16 (1.9%), moxifloxacin R: 1 (0.1%), cotrimoxazole I: 17 (2%) and R: 31(4%). Non-susceptibility to at least 1 agent was not correlated with age, clinical manifestation, underlying diseases and outcome. The serotype distribution differed between non-susceptible and susceptible strains. The serotypes in the 7-valent pneumococcal conjugate vaccine covered 42% of all infections and 73% of those caused by non-susceptible strains. In conclusion, the impact of antibiotic resistance in invasive pneumococcal disease remains limited in south-west Sweden.

The aim of this study was to determine the frequency and persistence of Staphylococcus aureus carriage in the throat in relation to anterior naris carriage. By use of a sensitive enrichment broth, S. aureus was cultured from the two sites from 259 patients upon admission to an orthopedic ward and from 87 staff members of the same ward. The throat was the most common carriage site in both groups. Forty percent of the patients and 54% of the staff were positive for S. aureus in the throat, compared to 31% and 36%, respectively, in the anterior nares. To determine the persistence of carriage, 67 individuals were repeatedly sampled from the anterior nares and the throat over 2 years (5 to 10 sampling occasions; mean, 7.8). The majority, 58% (39/67), were defined as persistent carriers of S. aureus, considering culture results from both sites. Of the 39 persistent carriers, 15 individuals were culture positive from only the throat on more than half of the sampling occasions (these are called preferential throat carriers) while only 5% (two individuals) were preferential anterior naris carriers by use of the same definition. Typing of the collected S. aureus isolates by pulsed-field gel electrophoresis revealed that the same strain of S. aureus was present, over time, in the throat of an individual at least to the same extent as in the anterior nares. Throat carriage was at least as persistent as carriage in the anterior nares.

Pneumococci isolated from blood and cerebrospinal fluid from 1998 to 2001 in 2 counties in south-west Sweden were serotyped with the capsular reaction test. Of the 836 strains, 353 (42%), 598 (72%) and 789 (94%) belonged to serotypes included in the 7- and 11-valent pneumococcal conjugate vaccines and in the 23-valent polysaccharide vaccine, respectively. The most common serotype was type 1 (119 isolates) followed in descending frequency by serotypes 7F, 9V, 14, 4 and 12F (90-49 isolates per serotype). The coverage rates of the 7- and 11-valent conjugate vaccines among 58 strains isolated from children and adolescents 0-19 y of age were 46% and 93%, respectively. A comparison of clinical characteristics of infections caused by different serotypes showed that types 1 and 7F were less commonly associated with severe underlying diseases, that patients infected with these serotypes were younger than the average and, thus, had a lower case-fatality rate.

Based on clinical and laboratory surveillance data, trends in the incidence rates of genital Chlamydia trachomatis infections in Sweden between 1991 and 1999 were analysed according to age group and sex. The influence of changes in laboratory methods on the reported infections was assessed. After a decrease in the incidence rate of infection of 36% between 1991 and 1994, followed by a period of stability, a 20% increase was observed between 1997 and 1999 (from 157 to 189/100,000). Between 1991 and 1999 the female:male ratio decreased from 1.7 to 1.4. Incidence rates started to increase in 1994 in the 15-19 y age group for both sexes. Crude Chlamydia positivity increased from 4.1% (352,050 people tested) in 1994 to 5.4% (305,946 people tested) in 1999. This increase in Chlamydia positivity was seen both in laboratories that had changed to more sensitive methods and in those that had not. Changes in laboratory methods can therefore only partially explain the increase in notified cases. Increased screening of men may have contributed to the increase, but rising incidence rates in all young age groups of both sexes suggest a true increase in prevalence.

Objective: To assess whether routinely collected data from partner notification for HIV infection could be used to study HIV epidemiology. The issues addressed were measures of contact patterns and behaviour change, variables influencing transmission risks, and indications of HIV incidence., Design: We collected anonymous questionnaire data from all partner notifications performed from seropositive patients diagnosed in Sweden between 1 January 1989 and 30 June 1990., Method: A structured questionnaire was completed by the physician or counsellor interviewing newly diagnosed seropositive patients and counselling their reported partners. The questions focused on temporal and behavioural aspects of all contacts between index patients and partners., Results: Questionnaires were completed for 365 of the 403 (91%) index patients diagnosed during the study period, for 350 of the 390 (90%) located partners, and for 274 of the 297 (92%) relationships where results of HIV testing were known for index patient and partner. Seropositive individuals diagnosed in 1989 or later reported less risk behaviour than those diagnosed earlier. Risk of transmission in sexual contact increased when the infectious partner developed symptoms of HIV infection. Anal intercourse was found to be approximately twice as infectious as vaginal, and transmission risk from a seropositive insertive partner approximately twice as high as from a receptive. The total HIV incidence in Sweden appears to be declining, as does the number of newly diagnosed infected homosexual men., Conclusion: Carefully collected data acquired from a partner notification programme are well suited to describe and follow the epidemiology of HIV infection.

Over a period of 19 months, Bacillus species, most frequently B. cereus, were isolated from postoperative and post-traumatic wounds in 24 patients on orthopaedic wards in a Swedish hospital. Clinical signs of infection were found in all but 3 patients: in 9 patients, mild signs with increased secretion from the wounds; in 10 patients, moderate signs with fever and/or significant local reaction around the wounds; and in 2 patients, severe signs with necrotic infections. Bacillus spp. were isolated from one-fourth of all patients with wound complications following total hip arthroplasty. Their hospitalization was significantly prolonged, compared with a control group (p = 0.0042). Isolates of B. cereus from wounds should not be dismissed as contaminants or as non-pathogenic, but must be assessed in the light of the clinical situation.

Sexually transmitted diseases (STD), whether old or new, impose a heavy economic burden on the public health service. Behavioural changes that could reduce the incidence of STD in the general population take time to make their effects felt. Common and treatable diseases such as genital chlamydial infections can and should be tackled by the old familiar strategy for combatting STD, viz. case finding, diagnosis, contact tracing and treatment, parallel with counselling in sexual behaviour. The incidence of infection is largely dependent on the number of asymptomatic individuals with a chlamydial infection in the population. Case finding programs devised chiefly for young, sexually active people will thus directly influence the natural life of Chlamydia trachomatis in our society. One such program, involving the sampling of women below the age of 30 when they come to the family planning clinic (FPC) for contraceptive advice, when applying for legal abortion, or when receiving prenatal care has been running in Halmstad, with increasing effect, since 1982. Contact tracing is an important part of the program. The prevalence of infected women has been halved since 1984 in the age interval 15-29 years. 10% of infected females, 15-24 years old, evidence repeated infection during 1 year. This program, carried out at a FPC, has proved cost-effective, achieving a 44% reduction in calculated expenditure. Chlamydial infections in Sweden are changing in character from being an untreated hyperendemic disease up to the late 1970s, to become a treated hyperendemic disease, until at last a declining prevalence can now be discerned.

Erythromycin-resistant group A streptococci (ERGAS) are considered rare in Sweden. In the county of Halland (240,000 inhabitants) in southern Sweden, we had 294 isolates of ERGAS between January 1984 and June 1985. Almost all strains were of T-type 12 and only resistant to erythromycin (MIC values approximately 8 g/l). Seven child day care centres (DCC) were involved in the outbreaks and on average 49% of all children were infected in each outbreak. Employees were seldom infected (8%), but parents and siblings more often (23% and 36%). One course of phenoxymethylpenicillin succeeded in eradicating ERGAS from 75% of those infected. The ERGAS strains are now established in southern Sweden and account for about 2% of all group A streptococcal infections in the county of Halland.

Microcalorimetry was used to study the kinetics of the actions of various tetracyclines on a strain of Escherichia coli. Differences in the capacity to suppress the metabolism of this bacterium were observed. When the antibiotic was present from the start of the experiment, a heat production of 2.0 muW/ml was registered after 12.5 h using minocycline; the corresponding figures for doxycycline, oxytetracycline, and tetracycline were 7.3, 6.6, and 4.5 h, respectively. In these experiments, equal concentrations, i.e., half the minimum inhibitory concentration (MIC), of each drug were used. The MIC for all the tetracyclines tested, determined by the broth dilution technique, was 0.8 mug/ml. In other experiments, the antibiotic (concentration, 1.6 mug/ml = 2x MIC) was introduced into the growth vessel during the logarithmic growth phase of the organism. The extent and duration of the inhibitory effect on the metabolism, as judged from the decrease in heat production, varied with the different tetracyclines. Immediately after introduction, minocycline, doxycycline, oxytetracycline, and tetracycline decreased the heat production in decreasing order of potency. With tetracycline, the heat production rose after about 1 h, and with minocycline it rose after about 9 h. The heat production remained at a low level for at least 19 h when using doxycycline and oxytetracycline. The results indicate that microcalorimetry offers a means for studies of the kinetics of the antibacterial actions of antibiotics and provides information that cannot be obtained by conventional bacteriological techniques. This information may be of use, in conjunction with pharmacokinetic data, in establishing optimum doses and dose intervals in antibiotic therapy.

We examined the prevalence of Chlamydia trachomatis in the cervix and the fallopian tubes of patients with acute salpingitis. Cycloheximide-treated McCoy cells were used as the growth medium. For purposes of comparison, women with infections confined to the lower genital tract and women without signs of genital infections were also studied. C. trachomatis was isolated from the cervix in 19 of 53 patients with acute salpingitis, in one of 18 lower-genital-tract infections and in none of 12 without signs of genital infection. C. trachomatis was recovered from six of the 20 valid specimens from the fallopian tubes of the patients with acute salpingitis. Our results indicate that chlamydia is a common etiologic agent in acute salpingitis.

Brushes (Cytobrush, Medscand) are superior to swabs for the collection of endocervical cells for cytologic examination. In the present randomized study, Cytobrush was compared with ENT-swabs and with white, cotton-tipped swabs to obtain samples for the diagnosis of chlamydial cervicitis. The women were examined for the presence of mucopurulent cervicitis (MPC). The subjects comprised 126 women, most of whom had been referred because of asymptomatic chlamydial infection. Specimens obtained with brushes were culture-positive in 83 women and positive in a direct fluorescent antibody test (FA-test) in 78 women. The corresponding figures for samples obtained with swabs were 80 and 74, respectively. The mean number of inclusions was significantly higher in samples obtained with brushes (4,999), compared with swabs (3,155), as was the mean number of elementary bodies (3,000 vs 2,481). MPC was detected in 65% of the women with asymptomatic chlamydial cervicitis, and in 93% of those with symptomatic infection. The corresponding figures for a pathologic wet smear were 62% and 80%, respectively. The specificity and predictive values of a positive and negative MPC-test was 21%, 39%, and 86%, respectively, and for a pathologic wet smear 53%, 44%, and 85%, respectively. We conclude that brushes are superior to swabs for sampling material, both for culture and for direct FA-tests. The MPC and the wet smear tests could be of value in the diagnosis of chlamydial cervicitis, providing confirmatory laboratory tests are used.

The kinetics of the antibacterial actions of cephalexin and cephaloridin against a strain of Escherichia coli and a strain of Staphylococcus aureus were studied by a flow microcalorimeter. The heat production was related to the number of viable organisms (CFU ml-1), the pH, the optical density of the culture medium (OD540), and the morphology of the antibiotic-exposed bacteria. No heat effects could be registered when the number of CFU was below 10(4) ml-1. The addition of cephalexin, 2.5 microgram ml-1 (5 x MIC), to cultures of S. aureus caused a decrease in the heat production which was only roughly correlated with the number of CFU ml-1. This was also the case when 9.0 microgram ml-1 (2 x MIC) of this drug were added to cultures of E. coli. Two to three hours after the drugs had been added, no heat effects could be registered for the following 6--8 hours, after which an increase in the heat production again occurred. The MIC and MBC of the organisms isolated during this late heat increase were 8--40 times higher than those of the parent test organisms. A direct relation between drug concentration and response, i.e. heat effects produced, was found when increasing concentrations of cephalexin, i.e. 1.0 up to 50 micrograms ml-1 (2--100 x MIC) were added in the logarithmic growth phase to cultures of S. aureus. In ampoule calorimetric experiments, E. coli was cultured in a non-aerated, sealed growth vessel in the presence of cephalexin or cephaloridin in concentrations corresponding to 1/2 x MIC. The thermograms did not differ in shape, although the heat effects occurred somewhat later in the culture containing cephaloridin.

16 patients with the anginose type of infectious mononucleosis were treated with metronidazole, and another 3 patients were given clindamycin. Most of the patients had been given penicillin or erythromycin before admittance to hospital. Treatment with metronidazole had a favourable effect on the course of the disease; the body temperature was normalized, signs of tonsillitis disappeared and cervical lymph nodes decreased in size within 3 days in 10 patients and in the remaining 6 within 4 or 5 days. Difficulty in mastication and swallowing was usually relieved within 1 to 2 days of treatment. The period before normalization was significantly shorter than in 10 controls. Two of the 3 patients who were given clindamycin developed exanthems, but otherwise a similar favourable effect as in the metronidazole-treated patients was observed.

Chlamydia trachomatis was isolated from the epipharynx of a 10-week-old baby girl taken ill with pneumonia but without signs of conjunctivitis. The infant developed specific antibodies to the organism. The course of the pneumonia was protracted, with cough and tachypnea. The baby, who was afebrile, improved on antibiotic therapy but pulmonary infiltrates persisted for several months. To our knowledge, this is the first case of pneumonia in an infant associated with C. trachomatis infection reported elsewhere than North America.

Recurrent urinary tract infections are known to occur among 5 per cent of all females. These women frequently have episodes of symptoms of lower urinary tract infection even between periods of bacteriuria. In the present study, 25 women with a history of recurrent urinary tract infections, found to lack signs of obstructive uropathy, were subjected to an extensive urological and microbiological survey. The investigation showed that (i) "pyuria" was common (9/12) but usually of urethral origin, (ii) introital and/or urethral colonization with Enterobacteriaceae often (11/25) occurred, (iii) apart from Escherichia coli found in three patients, a Bacteroides species was isolated in two and ureaplasmas in one patient from suprapubically aspirated urine, and (iv) chlamydia, gonococci, and trichomonads were not found. The patients were given methenaminehippurate for 1 week and then reexamined. The treatment did not seem to influence the indigenous flora of the lower urogenital tract.

The risk of infection for mother and baby after spontaneous rupture of the membranes was evaluated in a prospective study of 24 patients with ruptured membranes before the 36th week of pregnancy. The mean length of pregnancy after rupture was 10 days and 2 hours. Only patients harboring Group B streptococci or E. coli in the urogenital tract were treated with antibiotics (during delivery). With the exception of 1 woman, all patients harbored one or more pathogens in the urogenital tract. Four mothers were infected but all recovered. One of 26 infants died from infection. The study did not confirm any association between prolonged rupture of the membranes and the frequency of idiopathic respiratory distress syndrome, nor did it contradict attempts to actively prolong pregnancy after rupture of the membranes.

The heat effects produced by a strain of Escherichia coli in the presence of doxycycline and tetracycline were determined by calorimetric measurements using batch and flow microcalorimeters of the heat-conduction type. There was a clear difference in the capacity of the two tetracyclines to suppress the metabolism of the test bacterium as indicated by the heat production registered. In the presence of doxycycline or tetracycline in a concentration of 0.4 mug/ml (half the minimum inhibitory concentration, MIC), the time interval between the start of the experiment and a heat production of 2 muW/ml was 4.5 h for tetracycline and 7.3 h for doxycycline. When the antibiotics, in a concentration of 1.6 mug/ml (2 X MIC), were added to the culture during the logarithmic growth phase, tetracycline depressed heat production much less than doxycycline. Almost immediately after the addition of the two tetracyclines studied, heat production decreased sharply. The heat production rose again 1 h after tetracycline had been added, but remained at a low level for at least 16 h after doxycycline.--The results suggest that there are differences in the kinetics of the antibacterial action of doxycycline and tetracycline. Microcalorimetric studies provide new information for determining antibacterial activities of antibiotics, information that cannot be obtained by means of conventional bacteriological techniques. Such studies might be of value for the establishment of optimal dose regimens.