Hematogenous Complications Research Articles

Central venous catheter-related bloodstream infections: Epidemiology and risk factors for hematogenous complications

BackgroundCentral catheter-related bloodstream infections (CRBIs) can lead to severe complications, including suppurative thrombophlebitis, endocarditis, and metastatic infections. While complications due to CRBIs caused by Staphylococcus aureus (SA) are well-known, there are limited data regarding CRBIs caused by other bacteria. MethodsThis 2-year retrospective single-center study of patients with CRBIs from a tertiary care hospital examined the hematogenous complications associated with CRBIs according to patient characteristics, central venous catheter (CVC) types, and causative bacteria. ResultsAll in all, 254 patients with confirmed CRBIs were included; 285 bacteria types were isolated, mainly Enterobacteriaceae (n = 94), coagulase-negative Staphylococci (CNS, n = 82), SA (n = 45), and non-fermenting Gram-negative bacteria (NGB, n = 45). Among the patients, 35 developed at least one hematogenous complication (14 %), including suppurative thrombophlebitis (n = 15), endocarditis (n = 7) and metastatic infections (n = 16). In multivariate analysis, hemodialysis, persistent bacteremia for at least 3 days, and CRBIs caused by SA were associated with increased risk for hematogenous complications, while previous curative anticoagulant treatment was associated with reduced risk. Diabetes, CVC maintenance, and hematogenous complications were associated with increased 3-month mortality. ConclusionA thorough investigation of hematogenous complications should be envisioned in patients with persistent bacteremia, particularly those with SA infections and those on hemodialysis.

Peripheral venous catheter-related bloodstream infection is associated with severe complications and potential death: a retrospective observational study

BackgroundThe purpose of this study was to identify the clinical characteristics and outcomes of peripheral vascular catheter-related bloodstream infections (PVC-BSIs) and determine the risk of severe complications or death.MethodsWe performed a retrospective observational study from June 2010 to April 2015 at two regional university-affiliated hospitals in Tokyo. We studied the clinical manifestations, underlying diseases, laboratory results, treatment methods, recurrence rates, and complications in 62 hospitalized patients diagnosed with PVC-BSIs by positive blood cultures.ResultsThe median time from admission to bacteremia was 17 days (range, 3–142 days) and that from catheter insertion to bacteremia diagnosis was 6 days (range, 2–15 days). Catheter insertion sites were in the arm in 48 (77.4%) patients, in the foot in 3 (4.8%) patients, and in an unrecorded location in 11 (17.7%) patients. Additionally, the causative pathogens were Gram-positive microorganisms in 58.0% of cases, Gram-negative microorganisms in 35.8% of cases, Candida spp. in 6.2% of cases, and polymicrobials in 25.8% of cases. Eight (12.9%) patients died within 30 days of their blood culture becoming positive. Patients who died of PVC-BSIs had a higher proportion of Staphylococcus aureus infection than patients who survived (odds ratio, 8.33; p = 0.004).ConclusionsPVC-BSIs are a significant cause of health care-associated infection. We observed cases of severe PVC-BSI requiring intensive and long-term care along with lengthy durations of antibiotic treatment due to hematogenous complications, and some patients died. For patients with PVC-BSIs, S. aureus bacteremia remains a major problem that may influence the prognosis.

High vancomycin MICs predict the development of infective endocarditis in patients with catheter-related bacteraemia due to methicillin-resistant Staphylococcus aureus.

It has been suggested that there is an increased risk of treatment failure in episodes of MRSA bloodstream infection (BSI) caused by strains with high vancomycin MICs. However, it is unknown if this phenomenon may also act as a risk factor for the development of infective endocarditis (IE). We analysed 207 episodes of catheter-related (CR)-BSI recruited from June 2008 to December 2009 within a prospective study on MRSA BSI in 21 Spanish hospitals. Vancomycin susceptibility was centrally tested. The impact of high vancomycin MIC values (≥1.5 mg/L by Etest) on the subsequent development of IE was investigated by Cox regression. High vancomycin MIC values were observed in 46.9% of the isolates. Initial therapy consisted of vancomycin [99 episodes (44.7%)], daptomycin [25 (12.1%)], linezolid [18 (8.7%)] and other antistaphylococcal agents [16 (7.7%)]. Haematogenous complications occurred in 41 patients (19.8%), including 10 episodes complicated by IE. Early (48 h) and late (30 day) all-cause mortality were 3.4% and 25.1%, respectively. High vancomycin MIC isolates were more common among patients that developed IE compared with those free from this complication [90.9% (9/10) versus 44.7% (88/197); P = 0.007]. This association remained significant after adjusting for multiple confounders (including initial antibiotic therapy and catheter removal) in different models (minimum hazard ratio: 9.18; 95% CI: 1.16-72.78; P = 0.036). There were no differences in mortality according to vancomycin MIC values. Decreased susceptibility to vancomycin acted as a predictor of the development of IE complicating MRSA CR-BSI.

Pediatric acute osteomyelitis in the postvaccine, methicillin-resistant Staphylococcus aureus era

ObjectiveWe sought to describe the causative organisms, bones involved, and complications in cases of pediatric osteomyelitis in the postvaccine age and in the era of increasing infection with community-associated methicillin-resistant Staphylococcus aureus (MRSA). MethodsWe reviewed the medical records of children 12 years and younger presenting to our pediatric emergency department between January 1, 2003, and December 31, 2012, with the diagnosis of osteomyelitis. We reviewed operative cultures, blood cultures, and imaging studies. We identified causative organisms, bone(s) involved, time to therapeutic antibiotic treatment, and local and hematogenous complications. ResultsThe most common organism identified was methicillin-sensitive S aureus (26/55), followed by MRSA (21/55). Seventy-three bone areas were affected in 67 subjects. The most common bone area was the femur (24/73). Forty-six subjects had 75 local complications. The most common organism in cases with local complications was MRSA (49%). Three subjects had hematogenous complications of deep venous thrombosis, septic pulmonary embolus, and endophthalmitis. Subjects with complications had shorter time to therapeutic antibiotic treatment. When an operative culture was done after therapeutic antibiotics were given, an organism was identified from the operative culture in 84% of cases. ConclusionTreatment of pediatric osteomyelitis should include antibiotic coverage for MRSA. Most cases of pediatric osteomyelitis occur in the long bones. Hematogenous complications may include deep venous thrombosis and may be related to treatment with a central venous catheter. Operative culture yield when antibiotics have already been given is high, and antibiotic treatment should not be delayed until operative cultures are obtained.

Production of an attenuated phenol-soluble modulin variant unique to the MRSA clonal complex 30 increases severity of bloodstream infection.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and death. Phenol-soluble modulins (PSMs) are recently-discovered toxins with a key impact on the development of Staphylococcus aureus infections. Allelic variants of PSMs and their potential impact on pathogen success during infection have not yet been described. Here we show that the clonal complex (CC) 30 lineage, a major cause of hospital-associated sepsis and hematogenous complications, expresses an allelic variant of the PSMα3 peptide. We found that this variant, PSMα3N22Y, is characteristic of CC30 strains and has significantly reduced cytolytic and pro-inflammatory potential. Notably, CC30 strains showed reduced cytolytic and chemotactic potential toward human neutrophils, and increased hematogenous seeding in a bacteremia model, compared to strains in which the genome was altered to express non-CC30 PSMα3. Our findings describe a molecular mechanism contributing to attenuated pro-inflammatory potential in a main MRSA lineage. They suggest that reduced pathogen recognition via PSMs allows the bacteria to evade elimination by innate host defenses during bloodstream infections. Furthermore, they underscore the role of point mutations in key S. aureus toxin genes in that adaptation and the pivotal importance PSMs have in defining key S. aureus immune evasion and virulence mechanisms.

Understanding the Molecular Pathogenesis of Methicillin-Resistant Staphylococcus aureus

Staphylococcus aureus has been referred to as the “persistent pathogen” [1, 2] owing to its high prevalence for decades, its cause of a significant burden of disease, and its ability to cause a wide spectrum of clinical infections at various sites, including skin and soft tissue, bone and joint, heart valves, blood stream, and cerebrospinal fluid. These organisms possess numerous toxins and virulence factors that may account for their virulence and ability to evade host defenses [3, 4]. The acquisition by S. aureus of the staphylococcal cassette chromosome containing the mecA gene (SCCmecA), which encodes for methicillin resistance, has added to its armamentarium and increased the difficulty in its eradication in human infections [5,6]. The epidemiology of methicillin-resistant S. aureus (MRSA) is closely intertwined with that of methicillin-susceptible S. aureus (MSSA), and has become more complex with the recognition of healthcare-associated, healthcare-associated community-onset, and community-associated (CA) MRSA strains [4, 7, 8]. With the advent of numerous molecular typing methods has come an enhanced understanding of the complex evolution and epidemiology of MRSA [5, 9, 10]. There is a predominance of multilocus sequence type ST5 or clonal complex (CC) 5, with pulsed-field gel electrophoresis (PFGE) type USA100 as the most common healthcare-associated strains and ST8 or CC8 PFGE USA300 as the most common among communityassociated strains [8, 9]. Many of the MRSA strains are thought to have originated from predominant MSSA strains that acquired SCCmecA [6, 11]. The genotype classifications, while critical in elucidating the evolution, transmission, and epidemiology of both MSSA and MRSA infections in populations at risk, have only recently been recognized as potential predictors of specific clinical infections. As examples, in a large international data set of MSSA isolates, isolates causing infective endocarditis were more likely to be CC33 and to contain various adhesins and enterotoxins [12]. Furthermore, an analysis of both MSSA and MRSA isolates from one US academic medical center demonstrated that CC5 and CC30 strains were responsible for hematogenous complications of infection [13]. A predominant Asian strain of MRSA, ST239, was recently responsible for a large intensive care unit outbreak in London, and was highly associated with vascular access device-related bacteremia [14]. A related predominant Brazilian clonal complex of MRSA has been demonstrated to have enhanced ability to produce biofilm and adhere to and invade airway epithelial cells, properties that may promote its nosocomial transmission and ability to cause pneumonia [15]. In a study of patients with S. aureus bacteremia, CC15 was associated with 30-day mortality, and CC22 with osteoarticular infections [16]. These and other findings suggest that clonal typing may be a potential predictor of specific clinical infections. Additional research is needed to analyze the specific features and characteristics of individual clonal types that could be responsible for their predilection to cause or associate with specific types of clinical infections. One very important area of future research is linking the profiles of S. aureus toxins and virulence factors to specific genotypes. Because of their physiologic functions, specific toxins and virulence factors are probably the key to and the best predictors of important infection [3]. One of the most commonly cited factors in MRSA infections has been the PantonValentine leukocidin (PVL), a toxin [4, 17] that is found in many strains of CAMRSA and is cytotoxic to human and rabbit monocytes and macrophages and to human polymorphonuclear leukocytes. Received 11 October 2013; accepted 15 October 2013; electronically published 26 October 2013. Correspondence: Kurt B. Stevenson, MD, MPH, Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Ohio State University, N-1122 Doan Hall, 410 West 10th Ave, Columbus, OH 43210 (kurt.stevenson@osumc.edu). The Journal of Infectious Diseases 2014;209:488–90 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jit557

Klebsiella pneumoniae liver abscesses

Klebsiella pneumoniae liver abscesses

An Association Between Bacterial Genotype Combined With a High-Vancomycin Minimum Inhibitory Concentration and Risk of Endocarditis in Methicillin-Resistant Staphylococcus aureus Bloodstream Infection

Antimicrobial resistance and bacterial virulence factors may increase the risk of hematogenous complications during methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). This study reports on the impact of increasing vancomycin minimum inhibitory concentrations (V-MICs) and MRSA clone type on risk of hematogenous complications from MRSA BSI during implementation of an effective MRSA control program. In sum, spa typing, staphylococcal cassette chromosome mec allotyping, and vancomycin and teicoplanin MICs were performed on 821 consecutive MRSA bloodstream isolates from 1999 to 2009. Prospectively collected data, including focus of infection, were available for 695 clinically significant cases. Logistic and multinomial logistic regression was used to determine the association between clone type, vancomycin MIC (V-MIC), and focus of infection. MRSA BSIs decreased by ∼90% during the 11 years. Typing placed isolates into 3 clonal complex (CC) groups that had different population median V-MICs (CC30, 0.5 μg/mL [n = 349]; CC22, 0.75 μg/mL [n = 272]; non-CC22/30, 1.5 μg/mL [n = 199]). There was a progressive increase in the proportion of isolates with a V-MIC above baseline median in each clonal group and a disproportionate fall in the clone group with lowest median V-MIC (CC30). In contrast, there were no increases in teicoplanin MICs. High V-MIC CC22 isolates (1.5-2 μg/mL) were strongly associated with endocarditis (odds ratio, 12; 95% confidence interval, 3.72-38.9) and with a septic metastasis after catheter-related BSI (odds ratio, 106; 95% confidence interval, 12.6-883) compared with other clone type/V-MIC combinations. An interaction between clone type and V-MIC can influence the risk of endocarditis associated with MRSA BSI, implying involvement of both therapeutic and host-pathogen factors.

Methicillin-Susceptible Staphylococcus aureus Endocarditis Isolates Are Associated With Clonal Complex 30 Genotype and a Distinct Repertoire of Enterotoxins and Adhesins

Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity. IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes. 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05 for all). MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study.

CT Appearance of Pyogenic Liver Abscesses Caused byKlebsiella pneumoniae

To retrospectively compare the computed tomographic (CT) features of liver abscesses caused by Klebsiella pneumoniae with those caused by other bacterial pathogens. This retrospective study was approved by the institutional review board, with waiver of informed consent. Hospital records of all patients with a diagnosis of liver abscess between July 2003 and July 2010 were retrieved from an electronic hospital database. One hundred and thirty-one consecutive patients with confirmed pyogenic liver abscesses were studied. Data on clinical presentation, comorbid conditions, septic hematogenous complications, hospitalization duration, and abscess-related mortality were obtained. CT characteristics of abscesses including number, distribution, unilocular or multilocular appearance, cystic or solid appearance, gas in cavity, pylephlebitis, thrombophlebitis, and pneumobilia were reviewed. Etiology was established by pus and/or blood culture. Patients were placed into a monomicrobial K pneumoniae liver abscess group and a comparison group. A comparison of the CT features and clinical findings between the two groups was performed. The χ(2) analysis or Fisher exact test was used for categorical variables, and Student t and log-rank tests were used for continuous variables. A P value of less than .05 was considered to indicate a significant difference. Monomicrobial K pneumoniae liver abscesses were present in 92 cases (70.2%). On CT images, characteristics more likely to be associated with monomicrobial K pneumoniae liver abscesses than other pyogenic liver abscesses were a single abscess (79.3% vs 56.4%, P = .01), unilobar involvement (82.6% vs 61.5%, P = .01), solid appearance (57.6% vs 35.9%, P = .03), multilocular (94.6% vs 71.8%, P = .01), association with thrombophlebitis (30.4% vs 5.1%, P < .01), and hematogenous complications (28.3% vs 7.7%, P < .01). Thrombophlebitis was associated with higher incidence of hematogenous septic complications (50.0% vs 13.9%, P < .001). Monomicrobial K pneumoniae liver abscesses were associated with significantly shorter duration of antibiotic treatment (P = .018) and hospital stay (P = .005), but there was no significant difference in incidence of septic shock and abscess-related mortality as compared with other pyogenic liver abscesses. Monomicrobial K pneumoniae liver abscesses appear as single, solid, or multiloculated liver abscesses and are associated with thrombophlebitis and septic hematogenous complications.

Potential Associations between Hematogenous Complications and Bacterial Genotype inStaphylococcus aureusInfection

The impact of bacterial clonality on infections caused by Staphylococcus aureus is unclear. Three hundred seventy-nine S. aureus isolates (125 methicillin-resistant S. aureus [MRSA] and 254 methicillin-susceptible S. aureus [MSSA]) were genotyped by spa typing and multilocus sequence typing. For MRSA isolates, the staphylococcal chromosomal cassette mec (SCCmec) element was also typed. Three clinical categories were identified: nasal carriage only (n=118), uncomplicated infection (n=104), and bacteremia with hematogenous complications (n=157). By use of eBURST, 18 clonal complexes (CCs) were found in 371 isolates. Eight CCs accounted for 89% of isolates and occurred in all clinical categories. CC5 (P=.0025) and CC30 (P=.0308) exhibited a significant trend toward more frequent hematogenous complications. Isolates within spa types 2 and 16 showed the same significant trend and grouped within CC5 and CC30, respectively. SCCmec II isolates also showed the same significant trend compared with SCCmec IV; 96% were CC5 or CC30. Although most S. aureus genotypes exhibited the capacity to cause invasive disease, strains within CC5 and CC30 exhibited a significant trend toward increasing levels of hematogenous complications. Isolates within these CCs were also implicated by use of spa and SCCmec typing. The genetic determinants underlying these findings remain to be demonstrated.

Increased mortality among elderly patients with meticillin-resistant Staphylococcus aureus bacteraemia

Despite the high prevalence of meticillin-resistant Staphylococcus aureus (MRSA) infections among the elderly, outcomes of nosocomial MRSA bloodstream infections (BSI) for this patient population have not been fully examined. We performed a case-control study to compare outcomes of hospital-acquired MRSA BSI among patients >/=65 years of age (cases) with those younger than 65 years of age (controls). In a 430-bed tertiary-care teaching hospital, 100 hospitalized patients >/=18 years of age with S. aureus BSI were included in the study. Measurements obtained were: comorbidities, severity of illness at presentation, antibiotic therapy, haematogenous complications and mortality. Overall mortality was significantly higher among cases than controls [36% vs 12%; odds ratio (OR) 4.1, 95% confidence interval (CI) 1.4-14, P<0.01]. A pulmonary source was identified more frequently among elderly patients compared with younger controls (34% vs 16%; OR 2.7, 95%CI 1.1-8.1, P=0.04). On logistic regression, the following variables were independently associated with MRSA BSI among elderly patients: admission to a medical ward (OR 3.1, 95%CI 1.3-7.6, P=0.02), non-central-venous-catheter-related BSI (OR 3, 95%CI 1.2-7.6, P=0.02) and death (OR 3.7, 95%CI 1.3-11, P=0.02). Among patients who received vancomycin, more cases were treated with a reduced dose of vancomycin due to renal insufficiency compared with controls (64% vs 31%; OR 4, 95%CI 2-9, P=0.01). These data suggest that MRSA BSI is associated with significant mortality among the elderly population. Preventing MRSA acquisition among this patient population is of paramount importance.

Risk Factors for Hematogenous Complications of Intravascular Catheter-Associated Staphylococcus aureus Bacteremia

Risk Factors for Hematogenous Complications of Intravascular Catheter-Associated Staphylococcus aureus Bacteremia

Risk Factors For Hematogenous Complications of Intravascular Catheter--Associated Staphylococcus aureus Bacteremia

The role of both host and pathogen characteristics in hematogenous seeding following Staphylococcus aureus bacteremia is incompletely understood. Consecutive patients with intravascular catheter-associated Staphylococcus aureus bacteremia were prospectively recruited over a 91-month period. The corresponding bloodstream isolates were examined for the presence of 35 putative virulence determinants. Patient and bacterial characteristics associated with the development of hematogenous complications (HCs) (i.e., septic arthritis, vertebral osteomyelitis, or endocarditis) were defined. HC occurred in 42 (13%) of 324 patients. Patient characteristics at diagnosis that were associated with HC included community onset (relative risk [RR], 2.25; 95% confidence interval [CI], 1.24-4.07; P=.007), increased symptom duration (odds ratio for each day, 1.14; 95% CI, 1.06-1.2; P<.001), presence of a long-term intravascular catheter or noncatheter prosthesis (RR, 4.02; 95% CI, 1.74-9.27; P<.001), hemodialysis dependence (RR, 3.84; 95% CI, 2.08-7.10; P<.001), and higher APACHE II score (P=.02). Bacterial characteristics included sea (RR, 2.03; 95% CI, 1.16-3.55; P=.011) and methicillin-resistant S. aureus (MRSA) (RR, 2.09; 95% CI, 1.19-3.67; P=.015). Subsequent failure to remove a catheter was also associated with HC (RR, 2.28; 95% CI, 1.22-4.27; P=.011). On multivariable analysis, symptom duration, hemodialysis dependence, presence of a long-term intravascular catheter or a noncatheter device, and infection with MRSA remained significantly associated with HC. This investigation identifies 4 host- and pathogen-related risk factors for hematogenous bacterial seeding and reaffirms the importance of prompt catheter removal.

Pediatric tuberculosis pyramid and its fate with and without chemotherapy/chemoprophylaxis

The latest available information on total and infectious cases of tuberculosis in the country and also large number of sputum positive cases being detected annually, particularly after the involvement of multipurpose workers in the primary health care programme for the control of tuberculosis, is presented. The consequences of the large pool of infectious cases in the population lead to spread of bacilli to children with development of primary infection in them. These children with primary infection, specially high risk group in infancy and early childhood, get serious complications of the disease. It may be emphasized that BCG vaccination cannot prevent the lodgement of tubercle bacilli in the lung but can only contain or restrict haematogenous spread. Inspite of increasing coverage of infants with BCG vaccination there are an increasing number of cases of intrathoracic tuberculosis, particularly various groups of mediastinal nodes. However, to a lesser extent haematogenous complications do occur in malnourished children, as BCG has a limited value in preventing serious complications in children with malnutrition. The clinical pattern of pediatric tuberculosis has also changed in vaccinated and partly or inadequately drug treated children. Hence, chemoprophylaxis/chemotherapy to prevent complications of primary infection has been tried. Even relatively privileged children in developed countries are reported to have complications of primary infection to an extent of 10 to 15%, as per the studies all over world. So preventive chemoprophylaxis, preferably with two bactericidal drugs, should be considered as the main strategy for controlling primary infection. Chemoprophylaxis with two drugs should be used as incidence of isoniazid resistant bacilli has increased. All concerned with child health should consider the strategy of treatment of primary infection in high risk children by chemoprophylaxis by starting a large multicentric trial both in urban and rural areas, as a part and parcel of primary health care intervention already in practice for cases of sputum positive pulmonary tuberculosis.

Hautkomplikationen nach Pockenschutzimpfung

The local, contact, haematogenous and allergic complications of smallpox vaccinations are reviewed and grouped under the headings of early and late postvaccinial eruptions. Three patients are reported who after primary vaccination developed on the 14th, 20th and 22nd day respectively skin lesions in which virus could not be demonstrated. The morphology of these eruptions was essentially varioliform but may range from erythema multiforme and erythema nosodum to severe, haemorrhagic exanthemata.

Tuberculosis in Children and Adolescents: A Five to Fifteen Year Follow-up of 105 Patients

SUMMARY 1. In the 10 year period between 1939 – 1948 inclusive, there were 110 admissions at the Pollak Hospital through the age of 15 years for tuberculosis. This study is based on 105 (95.4 per cent) patients in whom clinical information was available five to 15 years after their first entrance into the hospital. 2. These cases are classified. Of the group of 55 (52.3 per cent of the total) with primary infection (parenchymal and/or glandular components), 47 (85.4 per cent) are alive and well five to 15 years later. The remainder (14.6 per cent) died from hematogenous complications (miliary and meningeal) in the pre-antibiotic era. 3. Of the group of 47 (44.8 per cent) with re-infection pulmonary disease, 32 (68 per cent) are living five to 15 years later (up to January 1, 1954) and all but two are inactive. Fifteen (32 per cent) in this group died; 12 from progressive pulmonary tuberculosis and three from tuberculous meningitis. The re-admission rate was 40 per cent compared to 7.4 per cent for the first infection cases. 4. The remaining three (all living) had extra pulmonary tuberculous foci without roentgen evidence of thoracic disease. 5. Prognostic factors in the primary infection and therapeutic measures in the re-infection groups are discussed. The best results in the latter patients were obtained with the use of bed rest and artificial pneumothorax.