Evaluation of in-vitro colistin susceptibility and clinical profile of carbapenem resistant Enterobacteriaceae related invasive infections.

PURPOSE: To determine the colistin susceptibility. To compare E-test vs broth-microdilution (BMD) method for invasive carbapenem resistant Enterobacteriaceae (CRE) infections. To study treatment options for the CRE. To analyze the clinical profile and outcome of CRE infections. METHODS: Antimicrobial susceptibility testing was performed for 100 invasive CRE isolates. Gradient diffusion and BMD methods were performed to determine colistin MICs. Essential agreement (EA), categorical agreement (CA), very major error (VME), and major error (ME) were worked out between BMD method and E-test. The clinical profile of patients was analyzed. RESULTS: The majority of the patients suffered from bacteremia [47(47%)]. Klebsiella pneumoniae was the most common organism isolated overall as well as among bacteremic isolates. 9(9%) CRE isolates were colistin resistant by BMD of which six were Klebsiella pneumoniae. There was 97% CA between E-test and BMD. EA was 68%. VME was found in three out of nine colistin resistant isolates. No ME was found. Among the other antibiotics tested for CRE isolates, the highest susceptibility was seen to tigecycline [43(43%)] followed by amikacin [19 (19%)]. The most common underlying condition was post solid organ transplantation [36(36%)]. A higher survival rate was seen among non-bacteremic CRE infections (58.49%) than bacteremic CRE infections (42.6%). Four out of nine patients with colistin resistant CRE infections survived and had a satisfactory outcome. CONCLUSION: Klebsiella pneumoniae was the most common organism causing invasive infection. Survival rates were higher in non-bacteremic CRE infections than bacteremic infections. Good CA was seen between E-test and BMD for colistin susceptibility, but the EA was poor. VME was more common than ME when E-tests were used for colistin susceptibility testing resulting in false susceptibility. Tigecycline and aminoglycosides are possible adjunct drugs for the treatment of invasive CRE infections.

Significance of Adopting Nucleic Acid Amplification Technique for Blood Donor Screening in a Resource Limited Setting: A Study from a Single Centre in South India.

Nucleic acid Amplification testing (NAT) has helped improve blood safety and detect window period and Occult Hepatitis B infections (OBI) This study was aimed at determining the following in blood donors: 1. seroprevalence of HIV, HBV & HCV, malarial parasite and Syphlis 2. NAT and seroyield for HIV, HBV and HCV 3. viral load in NAT yield donations 4. Pattern of HBV serological markers in HBV NAT yield donations 80,809 blood donations were screened over an 8 year period (2012-2019) for antiHIV I and II, HBsAg, antiHCV antibodies, malarial parasite and VDRL. Seronegative samples were tested by NAT using a multiplex PCR in a pool of six. NAT yield samples were tested for viral load and HBV serological markers. Seropositive samples were tested for NAT and checked for seroyield. SPSS windows version 24.0 was used for statistical analysis. 1.07% of blood donors were found to be seropositive with 0.08%, 0.86%, 0.09%, 0.03% and 0 for anti HIV I and II, HBsAg, antiHCV, VDRL and Malarial parasite respectively. Out of 79,938 seronegative samples, 20 samples (0.025%) were NAT positive for Hepatitis B with a NAT yield OF 1:3997. Out of the 20 NAT positive samples, 17 were OBI and three were window period infections. 14 NAT yield samples subjected to a HBV viral load assay showed a range of < 6-146 IU/ml. Minipool NAT in pools of six is able to indentify both OBI and window period infections. NAT could significantly improve the blood safety in a resource limited setting like India.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Multiple hepatic and splenic abscesses due to Burkholderia pseudomallei.

We report a case of melioidosis in an alcoholic and diabetic male patient presenting with multiple hepatic and splenic abscesses. Melioidosis is caused by an environmental bacterium Burkholderia pseudomallei. The clinical manifestations vary from asymptomatic infection to fulminant septic shock with abscesses in multiple internal organs. The treatment is prolonged with parenteral antibiotics in intensive phase followed by oral antibiotics in eradication phase till disease resolution. Due to varied clinical presentations, high index of suspicion coupled with adequate laboratory support is essential for rapid diagnosis and prompt initiation of optimal antibiotic therapy.

Efficacy of ß-lactam/ß-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

BACKGROUND: Whether active therapy with ß-lactam/ß-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/µL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

Convalescent plasma - Is it useful for treating SARS Co-V2 infection?

The world is challenged with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic. Although preventive measures such as social distancing, personal protective equipment and isolation would decrease the spread of the infection, a definitive treatment is still under way. Antivirals, immunisation, convalescent plasma (CP) and many more modalities are under trial, and there has been no definite answer to the management of COVID-19 infection. All patients so far have received the standard and symptomatic care. It is shown that the SARS-CoV 2 is a respiratory pathogen, and 80% of the infected patients would recover from the illness and it is the 20% of the infected patients require hospitalisation and even critical care. CP has been used to treat recent epidemic respiratory infections such as Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) infections with promising results. The CP of a recovered individual contains antibodies which neutralise the virus and decrease the viral replication in the patient. It is a classic adaptive immunotherapy and has been applied in the prevention and treatment of many infectious diseases. CP is plasma taken from a person who has recovered from an infection, which contains neutralising antibodies against the said infection. Giving CP to susceptible individuals or infected patients is a form of passive antibody therapy and in the case of SARS-CoV-2, is expected to provide protection by viral neutralisation and antibody-dependent cytotoxicity and phagocytosis. The adaptive response is to a specific antigen-binding array of molecules that are foreign to the host. The human response to viruses uses both the innate and the adaptive arms in its attempt to rid the host of the invading pathogen. The humoral response is a component of the adaptive immune response that allows for antibodies to bind to foreign invading pathogens, marks the pathogens and their toxins for phagocytosis and recruits further phagocytic cells to the site via the activation of the complement system and eventually prevents the pathogen from infecting target cells. Studies from Wuhan from various institutions during the research on COVID-19 infections during December 2019 have also shown promising results. Till date, randomised controlled studies for the use of CP in SARS-CoV-2 infection are lacking, and many countries have invited institutions to participate in clinical trials. The Indian Council of Medical research and the Central Drugs Standard Control Organisation, Government of India, have allowed the use of CP as an investigational drug under a trial basis. Internationally, agencies such as the USFDA, American Association of Blood Banks, European Blood Safety and British Blood Transfusion Society have also come out with various guidelines for the use of CP in COVID-19 infection. This article will review the current guidelines for the use of CP and compare the various guidelines of different agencies.

Two cases of Nocardia bacteraemia in solid organ transplant recipients.

Nocardiosis is an opportunistic infection occurring in immunosuppressed patients. While disseminated nocardiosis is common in immunosuppressed patients, Nocardia bacteraemia is rare. There are few reports of Nocardia bacteraemia following solid organ transplantation. We report two cases of Nocardia bacteraemia in solid organ transplant recipients-Nocardia cyriacigeorgica bacteraemia in liver transplant recipient and concomitant Nocardia farcinica bacteraemia and cyclosporiasis in a heart transplant recipient. Prompt recognition of early bacteraemia with initiation of antibiotic therapy may avoid the complications of disseminated disease in the solid organ transplant recipients.

Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia.

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

Invasive pneumococcal disease in children aged younger than 5 years in India: a surveillance study.

BACKGROUND: Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children younger than 5 years of age in India. We aimed to provide nationally representative data for the pattern of disease due to Streptococcus pneumoniae, trends in the serotype of invasive pneumococci, and invasive pneumococci antimicrobial resistance patterns, in India. METHODS: In this prospective hospital-based and retrospective laboratory-based surveillance study, we prospectively enrolled children aged younger than 5 years with suspected or proven invasive pneumococcal disease from 18 hospitals or institutional centres and retrospectively included laboratory-confirmed pneumococcal isolates from ten sentinel laboratories, together representing 11 states in India. Eligibility criteria were fever higher than 38°C without localising symptoms, clinical presentation of suspected meningitis or pneumonia, and evidence of radiographic pneumonia. We cultured blood and other normally sterile body fluids, reconfirmed and serotyped pneumococcal isolates, and established antimicrobial susceptibility using standard study protocols. FINDINGS: Between Jan 1, 2011, and June 30, 2015, we enrolled 4377 patients. Among 361 (8%) patients with culture-proven pneumococcal disease, all clinical data were known for 226 (63%); among these patients, 132 (58%) presented with pneumonia, 78 (35%) presented with meningitis, and 16 (7%) had other clinical conditions. 131 (3%) died overall and 29 (8%) patients with invasive pneumococcal disease died. Serotypes 14 (52 [14%] of 361), 1 (49 [14%]), 5 (37 [10%]), and 19F (33 [9%]) were the most common. Penicillin non-susceptibility occurred in isolates from 29 (8%) patients, co-trimoxazole resistance occurred in 239 (66%), erythromycin resistance occurred in 132 (37%), and chloramphenicol resistance occurred in 33 (9%). We found multidrug resistance in 33 (9%) of 361 patients. INTERPRETATION: The proportion of positive blood cultures, number of isolates, geographical representation, and data generated over the 4·5 years of the study are representative of data for most of India. Continued surveillance is warranted as the decision to introduce protein conjugated vaccine in India is made. FUNDING: GlaxoSmithKline India.

Clinical and Microbiology Profile and Outcome of Diarrhea by Coccidian Parasites in Immunocompetent Children.

BACKGROUND: Several studies have reported prevalence of pediatric coccidian parasitic diarrhea, but there is little information about their clinical profile, management and outcome. This study reviews the clinical profile and treatment outcome of coccidian parasitic diarrhea in immunocompetent children. METHODS: Five thousand one hundred and twenty-three immunocompetent children younger than 15 years of age presenting with acute diarrhea to a tertiary care pediatric hospital during a period of 4 years (2009-2012) were included in the study. Their demographic details and clinical course were recorded, and feces specimens received in the microbiology laboratory were subject to microbiology culture, wet mount microscopy, modified Ziehl-Neelsen staining to detect intestinal coccidian parasites and rotavirus sandwich enzyme-linked immunosorbent assay test (if age less than 2 years). RESULTS: The prevalence of coccidian parasitic diarrhea in immunocompetent children was 1.13% (58 cases) with Cryptosporidium spp. accounting for 1.09% (56 cases). Most Cryptosporidium infections were in children younger than 2 years [38 (67.85%)] and during the monsoon season [32 (57.14%)] with common clinical features being watery or liquid feces [44 (78.57%)], vomiting [40 (71.43%)] and fever [35 (62.5%)]. Thirteen (81.25%) of the 16 cases of cryptosporidiosis with dehydration were less than 2 years of age. Fifty-one (87.93%) of the 58 children were hospitalized. Thirty-eight (67.85%) children with cryptosporidiosis received empiric antimicrobial agents for suspected enteric bacterial and protozoan parasitic infection, which were discontinued after coccidian parasites were detected. Median duration of hospitalization was 2 days with no mortality reported. CONCLUSIONS: Coccidian parasitic diarrhea affects immunocompetent children of all age groups. Unnecessary administration of antimicrobial agents to these children can be avoided by routinely screening pediatric diarrheal fecal specimens for coccidian parasites by a cost-effective method such as modified Ziehl-Neelsen staining.

The accuracy and interobserver agreement in detecting the 'gallop sounds' by cardiac auscultation.

STUDY OBJECTIVES: To determine the observer accuracy and interobserver agreement in identifying S4 and S3 by cardiac auscultation and whether they improve with increasing observer experience. DESIGN: Prospective, blinded study. SETTING: Cardiology and general internal medicine wards in a university-affiliated teaching hospital. PATIENTS: Forty patients with a cardiac diagnosis and 6 patients without were studied. MEASUREMENTS AND RESULTS: Two cardiologists, one general internist, three senior and two junior postgraduate internal medicine trainees, blinded to the patients' characteristics, examined the patients and documented their findings on a questionnaire. Computerized phonocardiogram was obtained in all patients as a gold standard and was interpreted by a blinded, independent cardiologist. The mean positive predictive values for S4 and S3 were 51% (range, 24 to 100%) and 71% (range, 50 to 88%), respectively. The mean negative predictive values for S4 and S3 were 82% (range, 67 to 94%) and 64% (range, 56 to 85%), respectively. The overall interobserver agreements for detecting S4 was K = 0.05 (95% confidence interval [CI], 0.01 to 0.09) and S3 was K = 0.18 (95% CI, 0.13 to 0.24). There was no apparent trend in the accuracy or interobserver agreement with regard to the level of observer experience. CONCLUSION: The agreement between observers and the phonocardiographic gold standard in the correct identification of S4 and S3 was poor and the lack of agreement did not appear to be a function of the experience of the observers. The overall interobserver agreement for the detection of either S4 or S3 was little better than chance alone.

A lossless image compression algorithm using variable block size segmentation.

The redundancy in digital image representation can be classified into two categories: local and global. In this paper, we present an analysis of two image characteristics that give rise to local and global redundancy in image representation. Based on this study, we propose a lossless image compression scheme that exploits redundancy both at local and global levels in order to obtain maximum compression efficiency. The proposed algorithm segments the image into variable size blocks and encodes them depending on the characteristics exhibited by the pixels within the block. The proposed algorithm is implemented in software and its performance is better than other lossless compression schemes such as the Huffman, the arithmetic, the Lempel-Ziv and the JPEG.

Abnormalities in jugular venous flow velocity in pulmonary hypertension.

Doppler recordings of jugular venous flow velocity previously performed in this laboratory in patients with pulmonary hypertension had shown variations from the normal dominant systolic flow (SF) greater than diastolic flow (DF), to SF = DF, SF less than DF or DF alone. The mechanisms underlying these flow alterations were studied in 25 patients and correlated with hemodynamics. The patients with abnormal flow patterns had increased right atrial V-wave pressures. This was associated with an increased right ventricular early diastolic pressure. The incidence of clinical heart failure was higher in patients with SF less than DF or DF alone (8 of 11) compared with 5 of 10 patients with SF = DF. Thus, in patients with pulmonary hypertension, the abnormal jugular venous flow patterns appear to be caused by both an increased DF velocity and a decrease in SF velocity. Because the right atrial V-wave pressures were similar in patients with both SF = DF and SF less than DF or DF alone and the incidence of heart failure was higher in the latter, the decrease in SF must be a later phenomenon. Serial observations confirmed this temporal sequence. The applicability of these observations to bedside evaluation of patients with pulmonary hypertension is emphasized.

Changes in jugular venous flow velocity after coronary artery bypass grafting.

The factors underlying postoperative jugular venous flow velocity and pulse contour changes were studied in 25 patients undergoing coronary artery bypass grafting. Before operation, all patients had normal right-sided cardiac hemodynamics, normal jugular pulse contours and normal jugular venous flow velocity patterns, i.e., systolic flow (SF) velocity greater than diastolic flow (DF) velocity. After operation, jugular venous flow velocity was abnormal in 24 patients (SF = DF in 14 and SF less than DF in 10). Neither the right-sided cardiac pressures after the operation nor any of the perioperative factors examined had any bearing on these flow alterations. Postoperative right ventricular ejection fraction was normal in all 5 patients with SF greater than DF and SF = DF flow patterns (mean +/- standard error of the mean 48 +/- 3%). It was significantly depressed in all 6 patients with SF less than DF flow pattern (34 +/- 1%, 2p less than 0.001). These findings suggest that the right atrium behaves as a conduit rather than a capacitance chamber. However, the postoperative abnormal flow pattern of SF less than DF as opposed to SF = DF indicates the additional presence of right ventricular dysfunction. The implications of these observations for the clinical assessment of right ventricular function in the postoperative patients are discussed.

Prophylaxis of post-myocardial infarction dysrhythmias by long-term timolol therapy.

The antiarrhythmic efficacy of timolol maleate was assessed in 94 patients with acute myocardial infarction. No significant differences were noted between early treatment with timolol and placebo in the mean and peak hourly ventricular premature complex rates, ventricular premature complex couplets, or runs. However, compared to the placebo treatment, there was a significant (p less than 0.001) 66% reduction in the relative fraction of early-cycle ventricular premature complexes 7 to 9 days after initiation of timolol therapy and a more prolonged significant (p less than 0.001) 73% reduction in the fraction of early-cycle supraventricular complexes throughout the 28-day timolol and placebo comparison period. The frequency distribution of QRS duration was significantly different between the placebo- and timolol-treated patients, with the mean duration 8 msec longer in the placebo-treated patients (p = 0.008). Adverse effects from early administration of timolol did not differ from those in the placebo-treated patients.

Sarcoidosis simulating pulmonary veno-occlusive disease.

We describe a young woman who presented with a 6-month history of progressive pulmonary hypertension. At autopsy she was found to have noncaseating granulomas obliterating pulmonary veins, without granulomatous involvement of pulmonary arteries. Noncaseating granulomas were also present in the liver and hilar lymph nodes, confirming the diagnosis of sarcoidosis. To our knowledge this is the first reported case of pulmonary hypertension caused by sarcoidosis simulating pulmonary veno-occlusive disease.

The apical impulse in coronary heart disease.

Forty patients (36 with coronary artery disease), who had angiographic assessment of left ventricular function were studied using apexcardiography with a new method of standardization, the objective being to define the parameters of the apical impulse which reflect changes in the left ventricular function and correlate them with clinical assessment of the apical impulse. Based on measurements from patients with normal left ventricular function, abnormalities in apexcardiograms were identified. An increase in amplitude of percent A wave alone (greater than 13.3%) (palpable as an atrial kick in approximately half of these patients) was not associated with significant left ventricular dysfunction. An isolated abnormality in isovolumic slopes, although associated with mild left ventricular dysfunction, could not be detected clinically. Moderate to severe left ventricular dysfunction was always associated with abnormal ejection phase slopes and all had sustained apical impulses. The additional presence of a palpable atrial kick or an increased percent A wave on the apexcardiogram was more indicative of moderate rather than severe dysfunction. Thus this study clearly establishes that left ventricular function does in fact affect the nature of the apical impulse in patients with coronary artery disease and these can be easily defined.

Management of a malignant hyperthermia patient during cardiopulmonary bypass.

The anaesthetic management of cardiopulmonary bypass (CPB) for a patient with biopsy-proven malignant hyperthermia is reported. Specific changes in the technique used, such as venting the oxygenator before use, monitoring mixed venous PO2 and PCO2, as well as the safety of cold hyperkalaemic cardioplegia are described. Controversial aspects of malignant hyperthermia management such as the safety of calcium and catechol inotropes are discussed in relationship to the successful use of cardio-pulmonary bypass in our patient. We chose to treat left ventricular dysfunction by aggressive vasodilator (nitroglycerine) therapy. We detected no myocardial or respiratory depression secondary to dantrolene therapy either before or after operation.

Phosphorylation of dephospho-ATP citrate lyase by the catalytic subunit of cAMP-dependent protein kinase.

The native form of ATP citrate lyase (2 mol of phosphate/tetramer) and the dephospho-ATP citrate lyase (phosphate-free) purified to homogeneity from rat liver, are phosphorylated by ATP and by the catalytic subunit of cAMP-dependent protein kinase from rabbit muscle. A total of 2 mol of phosphate/tetramer were incorporated into native enzyme, while with the dephospho form, 4 mol of phosphate were incorporated. The phosphopeptides resulting from trypsin treatment which were isolated from phosphorylated forms of both native enzyme and the dephospho enzyme were similar. The ATP citrate lyase, phosphorylated to an extent of 4 mol of phosphate/tetramer, has the same Vmax as the native enzyme (2 mol of phosphate/tetramer). Native ATP citrate lyase, trypsin-treated to remove the phosphopeptide, could not be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase from rabbit muscle, suggesting a common trypsin-sensitive specific phosphorylation site. The phosphorylation rate varied with pH in potassium phosphate, imidazole/HCl, and Tris/HCl buffers. Divalent cations were essential for the activity of the protein kinase. The apparent Km value for ATP was found to be 50 microM.