Silvio Pitlik

Nontyphoid Salmonella Bacteremia: Age-Related Differences in Clinical Presentation, Bacteriology, and Outcome

In a retrospective study, 80 episodes of nontyphoid salmonella (NTS) bacteremia in children were compared with 55 episodes in adults over a 10-year period. The study disclosed major differences in the predisposition, clinical presentation, and outcome as well as the microbiology of NTS bacteremia in relation to age. Adults were more likely than children to have predisposing diseases (95% vs. 15%, respectively; P < .0001) and to receive prior medications (95% vs. 23%, respectively; P < .0001), particularly immunosuppressive agents (58% vs. 5%, respectively; P < .0001). In most adults (67%), NTS infection presented as a primary bacteremia and was associated with a high incidence of extraintestinal organ involvement (34%) and a high mortality rate (33%). In children, NTS bacteremia was usually secondary to gastroenteritis (75%) and caused no fatalities. Although group D Salmonella (78%) and the serovar Salmonella enteritidis were the predominant isolates from adults, the emergence of infections due to group C Salmonella (46%) and the serovar Salmonella virchow in children was noted.

Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials

Objectives To determine and quantify differences in efficacy between treatment regimens for brucellosis. Design Systematic review and meta-analysis of randomised controlled trials assessing different antibiotic regimens and durations of treatment for human brucellosis. Data sources PubMed, CENTRAL, Lilacs, conference proceedings, and bibliographies with no restrictions on language, study year, or publication status. Review methods Search, application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality independently performed in duplicate. Primary outcomes were relapse and overall failure resulting from primary failure or relapse. Relative risks with 95% confidence intervals were calculated and pooled with a fixed effect model. Results 30 trials and 77 treatment arms were included. Overall failure was significantly higher with doxycycline-rifampicin compared to doxycycline-streptomycin, mainly due to a higher rate of relapse (relative risk 2.80, 95% confidence interval 1.81 to 4.36; 13 trials, without heterogeneity). Results were consistent among patients with bacteraemia and complicated brucellosis. Doxycycline-streptomycin resulted in a significantly higher rate of failure than doxycycline-rifampicin-aminoglycoside (triple drug regimen) (2.50, 1.26 to 5.00; two trials). Gentamicin was not inferior to streptomycin (1.45, 0.52 to 4.00 for failure; two trials). Quinolones combined with rifampicin were significantly less effective than doxycycline combined with rifampicin or streptomycin (1.83, 1.11 to 3.02, for failure; five trials). Monotherapy was associated with a higher risk of failure than combined treatment when administered for a similar duration (2.56, 1.55 to 4.23; five trials). Treatment for six weeks or more offered an advantage over shorter treatment durations. Conclusions There are significant differences in effectiveness between currently recommended treatment regimens for brucellosis. The preferred treatment should be with dual or triple regimens including an aminoglycoside.

Relationship between Helicobacter pylori CagA status and colorectal cancer

OBJECTIVES:Infection with Helicobacter pylori, particularly with strains positive for CagA protein, increases the risk of gastric adenocarcinoma. Few studies have explored the possible association between H. pylori infection and colorectal cancer. This study evaluated whether the seroprevalence of CagA in H. pylori-infected patients affected risk for colorectal cancer independently of H. pylori status.METHODS:In this study, we tested serum IgG antibodies against H. pylori (ELISA) and CagA protein (Western blot assay) in 67 patients with colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). Colonic cancer and gastric cancer patients with H. pylori infection were compared to each control group and to the pooled controls using simple and adjusted analyses.RESULTS:H. pylori infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls, and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons between cases and controls). In the adjusted analysis, infection with H. pylori CagA+ compared to H. pylori CagA− was associated with increased risk for colorectal adenocarcinoma (odds ratio = 10.6; 95% CI = 2.7–41.3; p = 0.001) and gastric adenocarcinoma (odds ratio = 88.1; 95% CI = 6.3–1229.2; p = 0.001).CONCLUSIONS:Among patients infected with H. pylori, CagA+ seropositivity is associated with increased risk for both gastric and colonic cancer. This finding should stimulate additional research into the role of cagA+ H. pylori infection in the development of colorectal cancer.

Long-Term Outcome of Infective Endocarditis: The Impact of Early Surgical Intervention

To determine the impact of early surgical intervention on long-term survival in patients with infective endocarditis (IE), charts of all patients who had IE from January 1987 through December 1996 were reviewed. A total of 252 patients with definite or possible IE were included. Forty-four patients (17.5%) had early surgery on median hospital day 2 (range, 0-30 days), and 208 patients (82.5%) received medical treatment alone. On multivariate analysis, several variables, including early surgical intervention, improved long-term survival rates (hazard ratio, 1.5; P=.03), mainly in patients with Staphylococcus aureus etiology (P=.04). When patients with prosthetic devices were excluded, the median duration of survival for patients who had early surgery was >150 months, compared with 61.5 months for patients in the medical group (P=.1). Early surgical intervention compared with medical therapy alone is associated with increased short- and long-term survival rates in patients with IE, primarily when IE is caused by S. aureus.

Bacteremia in Adult Diabetic Patients

objective To compare the microbiology, sources, complications, and outcome of bacteremia in diabetic and nondiabetic patients. Research Design and Methods A prospective study was conducted of all episodes of bacteremia in hospitalized diabetic and nondiabetic patients. The study consisted of patients ≥ 18 yr of age with bacteremia detected within a 19-mo interval. Results We compared 124 episodes of bacteremia in 119 diabetic patients to 508 episodes in 480 nondiabetic patients. Diabetic patients were older than nondiabetic patients (median age 74 vs. 68 yr, P = 0.0001). In patients with an indwelling urinary catheter and bacteremic urinary tract infection, the percentage of Klebsiella in diabetic patients was 60% (6 of 10) and in nondiabetic patients was 17% (4 of 23, P = 0.04). In patients without an obvious source of bacteremia, the percentage of staphylococcal isolates in diabetic patients was 29% (10 of 35) and in nondiabetic patients was 14% (24 of 176, P = 0.04). Staphylococci were a common cause of bacteremic infections of the extremities in diabetic patients (12 of 19, 63%) and nondiabetic patients (20 of 50, 40%). Septic shock was the only complication that was more common in diabetic patients. The mortality in diabetic and nondiabetic patients was 28 and 29%, respectively. Conclusions Our results represent elderly patients with non-insulin-dependent diabetes mellitus. In this group, empirical treatment for suspected bacteremic urinary tract infection in patients with a urinary catheter should include coverage for Klebsiella. Empiric treatment for suspected bacteremia of unknown origin or caused by infection of the extremities should include an antistaphylococcal drug. The prognosis of bacteremia in diabetic and nondiabetic patients was similar.

Blood invasiveness of Salmonella enterica as a function of age and serotype

We explored the dual influence of the patients age and the infecting serotype on the blood invasiveness patterns of non-Typhi Salmonella enterica (NTS). Blood invasiveness ratio (BIR) was calculated as the ratio between the number of blood and blood + stool isolates. Analysis of 14,951 NTS isolates showed that the BIR increased drastically above the age of 60 years, reaching levels 3.5-7 times higher compared to age group < 2 years. Different patterns of age-related invasiveness were observed for the five most common NTS serotypes (Enteritidis, Typhimurium, Virchow, Hadar, Infantis). Among children < 2 years, the BIR was highest for serotype Virchow and lowest for serotype Hadar, while in persons > or = 60 years it was highest for serotypes Enteritidis and lowest for serotype Infantis. The tendency of NTS serotypes to invade the bloodstream was significantly influenced by the patients age, however the impact of age differed for various NTS serotypes.

Predicting Clostridium difficile toxin in hospitalized patients with antibiotic-associated diarrhea.

OBJECTIVE Clostridium difficile infection is implicated in 20%-30% of cases of antibiotic-associated diarrhea. Studying hospitalized patients who received antibiotic therapy and developed diarrhea, our objective was to compare the clinical characteristics of patients who developed C. difficile-associated diarrhea (CDAD) with those of patients with a negative result of a stool assay for C. difficile toxin. METHODS A prospective study was done with a cohort of 217 hospitalized patients who had received antibiotics and developed diarrhea. Patients with CDAD were defined as patients who had diarrhea and a positive result for C. difficile toxin A/B by an enzyme immunoassay of stool. The variables that yielded a significant difference on univariate analysis between patients with a positive assay result and patients with a negative assay result were entered into a logistic regression model for prediction of C. difficile toxin.Setting. A 900-bed tertiary care medical center. RESULTS Of 217 patients, 52 (24%) had a positive result of assay for C. difficile toxin A/B in their stool. The logistic regression model included impaired functional capacity, watery diarrhea, use of a proton pump inhibitor, use of a histamine receptor blocker, leukocytosis, and hypoalbuminemia. The area under the receiver operating characteristic curve for the model as a predictor of a positive result for the stool toxin assay was 0.896 (95% confidence interval, 0.661-1.000; P<.001), with 95% specificity and 68% sensitivity. CONCLUSIONS Our results may help clinicians to predict the risk of CDAD in hospitalized patients with antibiotic-associated diarrhea, to guide careful, specific empirical therapy, and to direct early attention to infection control issues.

A Large Q Fever Outbreak in an Urban School in Central Israel

BACKGROUND. On 28 June 2005, numerous cases of febrile illness were reported among 322 students and employees of a boarding high school located in an urban area in central Israel. Subsequent investigation identified a large outbreak of Q fever which started 2 weeks earlier. We describe the investigation of this outbreak and its possible implications. METHODS. We conducted a case-control study to identify risk factors for Q fever disease. Environmental sampling was conducted to identify the source and the mode of transmission of Coxiella burnetii, the infectious agent. RESULTS. Of 303 individuals, 187 (62%) reported being ill between 15 June and 13 July 2005. Serological evidence for C. burnetii infection was evident in 144 (88%) of the 164 tested individuals. Being a student, dining regularly at the school dining room, and boarding at school during a June religious holiday and the preceding weekend were all significant risk factors for contracting Q fever. C. burnetii DNA was detected using polymerase chain reaction on samples from the school dining rooms air conditioning system, supporting contribution of the air conditioning system to the aerosol transmission of the infectious agent. CONCLUSIONS. We report a large outbreak of Q fever in an urban school, possibly transmitted through an air conditioning system. A high level of suspicion for C. burnetii infection should be maintained when investigating point source outbreaks of influenza-like disease, especially outside the influenza season.

HYPERSENSITIVITY REACTION TO CHLORBUTOL-PRESERVED HEPARIN

Further blood cultures were taken. Gram-stained smears of the blood at 36 h showed scanty gram-negative (GN) rods, in four out of six bottles, which failed to grow on subculture. A generalised toxic erythematous rash compatible with penicillin hypersensitivity had also developed. Treatment was changed to cefuroxime I 5 g 8-hourly and amikacin 500 mg 8-hourly. Although the initial presumptive diagnosis was that this organism might be an aerobic opportunistic GN bacillus, the possibility that it could be an anaerobic GN rod was also considered, so GLC was done on 2 ml of blood from each of the blood culture bottles, from control uninoculated, and from inoculated blood culture bottles with no growth after 48 h using standard methods for the detection of short chain fatty acids.3 The chromatograms showed significant quantities of acetic, propionic, butyric, and succinic acids in the bottles in which GN rods had been seen, indicating the presence of anaerobic GN rods. The control bottles, apart from small amounts of acetic and lactic acid, were negative. IFA of smears from the positive blood culture bottles were tested with the pooled antisera of Bacteroides spp and anticapsular serum reported.2 There was positive fluorescence with both antisera identifying the organism as B. fragilis. Metronidazole was given intravenously (500 mg 8-hourly) for 24 h followed by metronidazole suppoositories 1 g twice daily which maintained serum levels of peak 26 4 and trough 24-3 3 mg/l. Amikacin was stopped. The dosages of cefuroxime and metronidazole were halved after 3 weeks. Therapy was continued for 6 weeks. The patient now made an uneventful recovery and was discharged after 7 weeks. In the rapid diagnosis of anaerobic infections, the use of GLC to detect short-chain fatty acids in specimens of pus is now well documented,l3-5 but its value in blood cultures is not yet well established,6,7 We previously reported the development and use of IFA in the rapid diagnosis of Bacteroicks infections,2 but IFA has not been applied to blood culture before. In this patient, using both techniques, the diagnosis was made within 2 h.

Osteomyelitis of the Ribs in the Antibiotic Era

A total of 106 cases of rib osteomyelitis were reviewed, including 2 cases described in detail. Mycobacterial and bacterial infections accounted for 47 cases each. Fungal rib osteomyelitis occurred in 11 cases and 1 case was caused by Entamoeba histolytica. Most cases occurred in children and young adults. The mean duration of symptoms before diagnosis was 16, 26 and 32 weeks for bacterial, mycobacterial and fungal rib osteomyelitis, respectively. Common clinical signs were fever (73%), soft tissue mass (64%) and chest pain (60%). Route of infection was defined in 85 cases: 62% from contiguous spread and 38% via haematogenous route of infection. Eighty-nine percent had a favourable outcome after antimicrobial therapy with or without surgery. In conclusion, rib osteomyelitis is a rare infection of various aetiologies. The majority of cases occur in children and young adults and its diagnosis is usually delayed for several weeks.A total of 106 cases of rib osteomyelitis were reviewed, including 2 cases described in detail. Mycobacterial and bacterial infections accounted for 47 cases each. Fungal rib osteomyelitis occurred in 11 cases and 1 case was caused by Entamoeba histolytica. Most cases occurred in children and young adults. The mean duration of symptoms before diagnosis was 16, 26 and 32 weeks for bacterial, mycobacterial and fungal rib osteomyelitis, respectively. Common clinical signs were fever (73%), soft tissue mass (64%) and chest pain (60%). Route of infection was defined in 85 cases: 62% from contiguous spread and 38% via haematogenous route of infection. Eighty-nine percent had a favourable outcome after antimicrobial therapy with or without surgery. In conclusion, rib osteomyelitis is a rare infection of various aetiologies. The majority of cases occur in children and young adults and its diagnosis is usually delayed for several weeks.