Review Article
Tropical Infections in the ICU
Vatsal M Kothari, Dilip R Karnad, Lata S Bichile

Certain arthropod-borne infections are common in tropical regions because of favorable climatic conditions.Water-borne infections like leptospirosis are common due to contamination of water especially during themonsoon floods. Infections like malaria, leptospirosis, dengue fever and typhus sometimes cause lifethreatening organ dysfunction and have several overlapping features. Most patients present with classicialclinical syndromes: fever and thrombocytopenia are common in dengue, malaria and leptospirosis;coagulopathy is frequent in leptospirosis and viral hepatitis. Hepatorenal syndrome is seen in leptospirosis,falciparum malaria and scrub typhus. The pulmonary renal syndrome is caused by falciparium malaria,leptospirosis, Hantavirus infection and scrub typhus. Fever with altered mental status is produced by bacterialmeningitis, Japanese B encephalitis, cerebral malarial, typhoid encephalopathy and fulminant hepatic failuredue to viral hepatitis. Subtle differences in features of the organ failure exist among these infections. Thediagnosis in some of these diseases is made by demonstration of antibodies in serum, and these may benegative in the first week of the illness. Hence empiric therapy for more than one disorder may be justified ina small proportion of cases. In addition to specific anti-infective therapy, management of organ dysfunctionincludes use of mechanical ventilation, vasopressor drugs, continuous renal replacement therapy and bloodproducts. Timely transfer of these patients to well-equipped ICUs with experience in managing these casescan considerably decrease mortality and morbidity. ©
Certain infections are commoner in the tropics due toclimactic conditions that favor arthropod vectorslike mosquitoes, or to exposure to contaminated water.
Patients present with certain well defined syndromeslike fever with thrombocytopenia, fever with hepatorenaldysfunction or fever with pulmonary-renal dysfunction.
Diseases that commonly present with fever andthrombocytopenia are malaria (usually falciparum butalso vivax), dengue fever, leptospirosis, rickettsialinfections and viral fevers
Medical Intensive Care Unit, Department of Medicine, SethGS Medical College and KEM College, Mumbai.
Thrombocytopenia occurs due to immune destruction,bone marrow suppression, DIC and sometimeshypersplenism. Drugs like quinine can causethrombocytopenia by immune mechanisms. The plateletcounts can fall to as low as 5000/mm3 predisposing thepatient to life threatening bleeding in the central nervoussystem or from the gastrointestinal and genitourinarytracts. Regular platelet transfusions to maintain a countof at least 20000/mm3 should be given until the thrombocytopenia resolves.
Both malaria and leptospirosis usually have anassociated derangement of the PT and APTT whereasdengue usually presents with thrombocytopenia. In aMumbai study of patients with severe falciparummalaria7 38% had thrombocytopenia of which 6%required platelet transfusions. The same study showedthat 7% had a DIC requiring blood component therapy.
Diseases that predominantly present withhepatorenal dysfunction are falciparum malaria,leptospirosis, scrub typhus and hepatitis E or A withfulminant hepatic failure and the hepatorenal syndrome.In pregnant patients hepatitis E commonly producesFHF. Patients are at increased risk of bleeding due todecreased clotting factor production by the liver, DICdue to liver failure and infection, and uremia-inducedplatelet dysfunction. Continuous renal replacementtherapy helps not only to clear the blood of uremic toxinsbut also helps remove excess bilirubin and othersubstances normally detoxified by the liver.
Renal failure in patients with severe malaria presentswith oliguria whereas patients with leptospirosisusually have a non-oliguric renal failure withhypokalemia due to tubular dysfunction. Patients who present with hepatorenal dysfunction are often treatedfor both malaria and leptospirosis until either 3 smearsfor malarial parasites are negative or leptospira antibodytests come positive. In a study published from Mumbai7the incidence of renal failure in patients with severefalciparum malaria was 30% with a mortality of 50%.30% of these patients required dialytic therapy. In thesame study hepatic failure occurred in 26% of patientswith a 49% mortality. A study again from Mumbaishowed that 70% of patients with severe leptospirosishad renal failure and 80% of those who died had intra-alveolar hemorrhages.11
Diseases that present with pulmonary-renaldysfunction are falciparum malaria, leptospirosis,hantavirus infection, scrub typhus and severepneumonias due to Legionella and the pneumococcus.Malaria causes an ARDS type of syndrome whilstleptospirosis can cause ARDS or alveolar hemorrhagewhich is due to a combination of alveolo-capillary injuryand thrombocytopenia. The X-ray in patients withleptospirosis often shows dense pulmonary infiltratesdue to the hemorrhage. A useful distinguishing featurebetween malaria and leptospirosis is the presence ofsignificant conjunctival hemorrhages in the latter. In theMumbai study quoted above respiratory failure occurredin 26% of patients with severe falciparum malaria and90% of these patients died.
Important diseases to consider are cerebral malaria,encephalitis, meningitis and typhoid fever besidesdiseases like brain abscess and septic encephalopathy.Elderly patients with UTI or pneumonia often presentwith altered sensorium and few other clinical signs.
Other Important Infections are tropical pyomyositisand enteric fever. Enteric fever can present withmultiorgan dysfunction and septic shock.
P. falciparum infects RBCs of all ages. The parasiteavoids splenic sequestration and destruction of infectedRBC’s. This occurs by the formation of knobs on the RBCmembrane.1,2 These knobs appear about 16 hours intothe asexual cycle and attach to specific receptors likeICAM-1 on the endothelium of capillaries in the brain,chondroitin sulfate in the placenta and CD36 in otherorgans.3,4 The infected RBCs also attach to uninfectedRBCs by a process called as rosetting. The attachmentto the endothelium of the capillaries and the rosetting causes the blockage of capillaries and venules and leadsto end-organ dysfunction. The infected cells eventuallyrupture and the contents cause macrophages to releasecytokines like TNF-alpha, which cause a febrile response.T Helper cells appear to play an important role in theimmune response. Temperatures >400 C damageparasites and cause synchronization of the parasiticcycle leading to a tertian fever pattern.
Infected individuals that survive develop a speciesand strain specific immunity that is both cellular andhumoral in nature. A study in South Africa revealed thatHIV positive patients with CD4 counts<200 had moresevere infections compared to HIV negative controls.6
Clinical features of severe falciparum malaria:5,8
Prognosis is related to the number of organ systemsinvolved with a study showing 6-7% mortality withsingle organ failure and 40-50% with involvement oftwo or more organs.7 This study also showed secondarybacterial sepsis is the major cause of death after day 7 inpatients with severe malaria
Cerebral malaria : Usually manifests as a diffusesymmetric encephalopathy without focal signs. Patientsoften have extensor posturing and upgoing plantars.Seizures may occur especially in children and cerebralvenous thrombosis or cerebral infarcts may be found.Cerebral malaria has a mortality of 30% in a series froma major public hospital.7
Acute renal failure : The etiology involvesmicrocirculatory abnormalities in the kidneys andpatients develop acute tubular necrosis that initially isoliguric in nature. Massive intravascular hemolysis cancause hemoglobinuria which also damages the tubules.These patients often require hemodialysis or CRRT todeal with the metabolic derangements of ahypercatabolic state.
Acute respiratory failure : A noncardiogenicpulmonary edema often develops about 4 days aftertherapy has been started.7 The pathogenesis involvesrelease of cytokines that increase capillary permeability.In this setting fluid administration should be guided byeither CVP or PCWP monitoring in order to preventworsening of the oxygenation status.
Hepatic dysfunction : Jaundice results from acombination of hemolysis, cholestasis and hepatocytedysfunction. Rarely hepatocyte dysfunction may besevere enough to cause hypoglycemia, coagulopathy,encephalopathy and lactic acidosis.
Hypoglycemia : This occurs due to reducedgluconeogenesis (and in the case of the liver reducedglycogenolysis), increased utilization of glucose by boththe host and the parasite and the use of insulinsecretagogues like quinine. Hypoglycemia maycontribute to CNS injury.
Acidosis : Lactic acidosis is secondary to increasedanerobic glycolyis in tissues with sequestered parasites,increased lactate production by parasites, decreasedlactate clearance by the liver and kidneys andhypotension
Hematologic derangements : Severe parasitemia canlead to a rapid fall in the hematocrit which if severeenough can give the urine a cola colour due to thepresence of free hemoglobin. Besides anemia, severethrombocytopenia with platelet counts <20,000/mm3may contribute to bleeding from the GI and GU tracts.DIC is common in severe malaria.
Poor prognostic indicators : Deep coma, convulsions,shock, anuria, hypoglycemia<45-50 mg/dl, Lactate>5mmol/L, creatinine >3.0 mg/dl, platelets<50,000/mm3,PCV<15% bilirubin>3.0 mg/dl, AST and ALT>3Xnormal, parasitemia>100000/microlitre in non-immuneindividuals
Diagnosis : Thick and thin peripheral smears fordegree of parasitemia and speciation.
Tests for detecting P. falciparum antigens. e.g. pf HRP-2 or LDH in blood from a finger prick. These tests usemonoclonal antibodies to capture the parasite antigensand are read out as coloured bands. Immunofluorescentmicroscopy and PCR are newer techniques for detectionof malaria
Treatment : IV quinine, IV artesunate or I.Martemether. Doxycycline may be added as an adjunct ifmalarial resistance to quinine or artemether derivativesis suspected. Treat hypoglycemia, blood and platelettransfusions, ventilatory therapy for ARDS and renalreplacement therapy for oliguric renal failure. In arandomized study from Vietnam, Phu et al found thatpatients with severe malaria treated by continuous renalreplacement therapy (CRRT) had a faster clearance ofacidosis and azotemia when compared to patients onperitoneal dialysis. The patients on CRRT had a lowermortality and CRRT was more cost effective whencompared to peritoneal dialysis.
This is a spirochetal disease caused by Leptospirainterrogans. The spirochetes also infect rats, dogs, cattle,sheep and swine. Infection occurs due to exposure tocontaminated water. The disease has an incubationperiod of 2-26 days with an average of 10 days.
Pathobiology relevant to the ICU
Most patients have a nonspecific febrile illness, butin a few the disease manifests with a severe illnesscharacterized by hepatorenal dysfunction often withpulmonary hemorrhage, called as Weil’s syndrome.9,10This usually develops 4-9 days into the illness. Theleptospires directly or through immune mechanisms damage blood vessels, cause centrilobular necrosis ofthe liver and renal tubular dysfunction by causing aninterstitial nephritis and acute tubular necrosis. Renalfunction recovers completely by 6 months in mostindividuals.
Clinical features : Patients characteristically haveconjunctival suffusion or hemorrhages and uveitis,severe muscle tenderness and non-oliguric renal failurewith hypokalemia
Besides severe hepatorenal dysfunction, patients canpresent with ARDS, myocarditis, rhabdomyolysis,thrombocytopenia, DIC, hemorrhage into the skin andinternal organs, uveitis, and digital gangrene.
An outbreak in Mumbai in 2000 revealed that 35% ofpatients had pulmonary manifestations. 80% of patientswho died had pulmonary hemorrhages and 70% hadrenal failure. Patients with conjunctival suffusion andpulmonary renal failure were more likely to be MATpositive.11
Laboratory findings : The white cell count is often<10,000 ranging from 3-26000. Urinalysis showsproteinuria, pyuria, granular casts and microscopichematuria. The CPK is often elevated, CSF may show anaseptic meningitis like picture and the chest x-ray oftenshows dense confluent shadows suggestive ofpulmonary hemorrhage.
Diagnosis is made with serology with the microscopicagglutination test (MAT) as the gold standard with eithera four fold rise in titres or a single titre of >1:800 beingdiagnostic. Other serologic tests being the ELISA and acommercially available dridot test which detects IgMantibody by an enzyme based dot immunoassay with asensitivity of 30% at 3 days and of 100% at 10 days intothe illness.12,13
The organism can be grown from the blood and theCSF in the first two weeks of the illness and from theurine in the third week onwards for upto a month.
Since the antibodies may not be demonstrable in serumduring the first week of illness, initial treatment is oftenempirical. In some patients it is virtually impossible todifferentiate between severe malaria and leptospirosis;this dilemma is compounded by the fact that the seasonalvariation in the incidence of these two disorders isidentical (Fig. 1). These patients may receive treatmentfor both disorders on admission. We usually discontinueantimalarial treatment if several blood smears formalarial parasites over the next 48 hours are negative.
Treatment involves the use of crystalline penicillin ata dose of 6 million units daily or ceftriaxone 1 gramevery 12 hourly.14,15 In penicillin allergic patientsintravenous doxycycline 100 mg every 12 hourly can beused. Since rickettsial diseases can mimic leptospirosisceftriaxone or doxycycline should be used when the diagnosis is in doubt.16
Other therapy involves supportive measures likedialysis, ventilation and the use of blood products.
An arbovirus disease transmitted by the bite of theAedes mosquito. The virus initially replicates in the skinand lymph nodes before dissemination in the bloodstream.17,18
Pathophysiology : The virus has an incubation periodof 4-7 days though can range from 3-14 days.
Usually it is a nonspecific febrile illness but certainfactors can predispose to severe manifestations likedengue hemorrhagic fever (DHF), or dengue shocksyndrome (DSS).
These factors are :

a.Infection with dengue virus serotype 219

b.Age less than 11 years20

c.Good nutritional status(since severe manifestationsare related to the host immune response,malnourished individuals are less prone to avigorous immune reaction to the virus)21

d.Subsequent infection with a different viral serotypedue to antibody dependant enhancement (ADE) ofviral entry into monocytes and macrophages,increased antigen-antibody complexes withsubsequent vascular injury and increased T cellresponses with immune activation.17,22

ADE occurs due to persistence of cross reactingantibodies from the previous infection. These antibodiesare unable to neutralize viruses from different serotypesbut after binding to the viruses enhance uptake via theFc receptors on monocytes and macrophages withsubsequent T cell activation.
The cascade of cytokines then causes endothelialinjury, platelet and clotting factor consumption andincreased vascular permeability.
A study from Mumbai showed that predictors of DSSin children were younger age, altered sensorium,paralytic ileus and significantly deranged PT. This samestudy showed a case fatality of 17% in DSS.23
There are 3 main clinical subsets of dengue infection18
Nonspecific febrile illness, classic dengue and dengue hemorrhagic fever/dengue shock syndrome
Classic dengue presents with fever and severeheadache and myalgias. Giving it the name of‘breakbone fever’.24 There may be associatedlymphadenopathy, pharyngeal and ocular congestionand respiratory or GI symptoms. The fever lasts for 4-5days and around the time of defervescence about half ofpatients develop a maculopapular rash that lasts 2-3days and may be pruritic. Rarely there may bemyocarditis, hepatitis, pneumonitis and bleeding intointernal organs.
Dengue hemorrhagic fever and dengue shocksyndrome occur due to increased capillary permeabilityand vasodilatation 3-7 days after start of illness, causedby mediators like TNF alpha and IL-1 released frominfected monocytes and macrophages. The capillary leakexplains the rise in the hematocrit, periorbital edemapleural effusions and ascites.
Capillary leak and thrombocytopenia may give apositive capillary test which is more than 20 petechiaein an area of 1 inch2 when the blood pressure cuff isinflated midway between systolic and diastolic bloodpressure for 5 minutes.25 Shock often occurs 24 hoursbefore or after defervescence supporting a role forimmune mediated injury. The shock lasts for a day ortwo and patients either die or get better. Encephalopathy,GBS and Acute transverse myelitis have also beenassociated with dengue virus infection.26,27
Leukopenia occurs due to a direct suppressant effecton the bone marrow. Thrombocytopenia occurs mainlydue to increased platelet destruction by adsorption ofvirus or antigen-antibody complexes on the plateletsurface with subsequent immune destruction.24
A coagulopathy may occur due to consumption ofcoagulation factors due to DIC, liver dysfunction andmolecular mimicry between the viral proteins andcoagulation factors.
Liver injury may occur due to direct invasion by thevirus or due to immune mediated injury.
Prognostic factors: BP<90/60, hematocrit >50 %,platelet count<50,000 bleeding other than petechiae e.g.ecchymoses, hematemesis or epistaxis Diagnosis18

a.The gold standard is the detection of antibodies byhemagglutination inhibition assay showing at leasta four fold rise in titre of neutralizing antibody inpaired samples.

b.ELISA test for IgM antibodies which appear aroundthe 6th day of illness and last from 1-3 months. IgGantibodies appear after 7-10 days and last for monthsto years, they too can be detected by ELISA. In secondary dengue IgG antibodies are present inhigh titre early in illness

c.Virus isolation techniques, which are not easilyavailable

d.RT- PCR :Detection of the virus within 1-2 days ofmanifestations with test being negative later in the illness

Treatment : Shock is treated with crystalloids likeDextrose normal saline/Normal saline or Ringer'sLactate given 10-20 ml/kg over 30 minutes then everyhour until pulse, BP, CVP and urine output normalize.Then the infusion rate is reduced. In profound shockinitially colloids like hetastarch or hemaccel may be used.In a study in children with dengue shock syndrome,although a marginally longer time to initial recovery wasseen with Ringer's Lactate, it was as effective as dextran70 and hetastarch in fluid resuscitation and significantlymore adverse events were encountered with the dextransolution.28
Platelet transfusions need to be given for symptomaticthrombocytopenia.
This bunyavirus infects vascular endothelium andcauses two major syndromes: Hemorrhagic fever withrenal syndrome (HFRS) and hantavirus cardio-pulmonary syndrome (HCPS). The virus is acquired byexposure to aerosols of rodent urine and saliva and alsofeces. The disease is found in the US, South America,Europe, Russia and China. A study from Vellore revealeda prevalence of 15% amongst patients who had presentedwith a febrile illness.29 Its manifestations can closelymimic either dengue or leptospirosis and hence deservesmention.30
Virus infection of the endothelium does not result insignificant injury. Like dengue it is the immune responseagainst viral antigens expressed on the endothelial cellsin the heart, lungs, kidneys and lymphoid organs thatcauses most of the damage. This immune response ismediated by T cells and macrophages which releasecytokines like TNF-alpha and IL-1 beta which increasecapillary permeability and cause leakage of protein richfluid into the interstitium. Nitric oxide release by TNFplays an important role in the vasodilation underlying the shock state. The virus may however damage renaltubules.31,32
Cardiopulmonary syndrome
The incubation period is about 3 weeks, the illnessbegins with non specific constitutional symptoms thatlast about 3-7 days, and this is then followed by acapillary leak syndrome that lasts 2-8 days causinghypotension and shock. Leak into the pulmonary bedcauses a noncardiogenic pulmonary edema that can leadto rapid hypoxia, arrhythmias and arrest. There may bea separate oliguric phase lasting 3-8 days which precedesa polyuric phase lasting for a variable period of time.33
Thrombocytopenia, leucocytosis(upto 90,000/mm3)with a left shift and increased immunoblasts (upto 10%of circulating lymphocytes) with an increased LDH ischaracteristic34 and should prompt diagnosis with morespecific tests like the ELISA for IgM and IgG antibodies.35
Treatment is mainly supportive with the use of IVfluids, inotropes, mechanical ventilation, extra-corporealmembrane oxygenation and blood products.36 The useof the nucleoside analogue ribavirin has not been shownto have significant benefit in HCPS.37
Hemorrhagic Fever with Renal Syndrome-HFRS
The manifestations of HFRS also have a similarpathophysiologic basis as HCPS.38
The renal manifestations are more prominent thanthe pulmonary, and renal injury occurs due to acombination of shock, immune injury and possible directinvasion by the virus, hemorrhagic manifestations maybe severe. Non specific constitutional symptoms arefollowed by shock, oliguria, DIC and hemorrhagicmanifestations. Survivors enter a diuretic phase by day10-14.
Diagnosis involves similar parameters as HCPS, andtreatment includes both supportive treatment (includingdialytic modalities) and the use of ribavirin.39
This is a rickettsial disease caused by Orientia.tsutsugamushi.
Pathophysiology : The organism is a Gram-negativecoccobacillus that infects vascular endothelium withsubsequent vascular injury in organs like the skin, liver,kidneys, meninges and brain. The vascular injury causesa DIC with platelet consumption, vascular leak,pulmonary edema, shock, hepatic and renal failure.40The organism is inoculated into the skin by the bite oflarval forms of tromiculid mites, these larvae are calledas chiggers. The disease occurs 7-10 days after the biteand patients present with fever, relative bradycardia,41severe myalgias, a nonpruritic maculopapular rashsometimes with an accompanying eschar and lymphadenopathy. The disease lasts for 2-3 weeks ifuntreated and complications due to vasculitis indifferent organs occur usually in the 2nd week of illness.
The diagnosis is made by history of exposure,appropriate physical findings, thrombocytopenia,deranged LFTs, elevated creatinine and serologyutilizing tests like IFA and ELISA . The Weil Felix reactionis now no longer used as a diagnostic tool.
Treatment is with either chloramphenicol ordoxycycline with often a rapid response to therapy.Doxycycline resistant strains may be treated with eitherchloramphenicol, azithromycin42 or the addition ofrifampicin.
This is an arbovirus encephalitis caused by aflavivirus that is transmitted to humans by the bite ofthe culex mosquito. Birds and pigs are the natural hostsof the virus and humans are dead end hosts. Theincubation period lasts from 5-14 days.
Pathophysiology : Most infections are asymptomaticwith about 1in 25 non immune adults having symptoms.The virus can infect brain parenchyma (especially thethalamus and basal ganglia) of the cerebral hemispheres,the brainstem and the anterior horn cells of the spinalcord.43 The spectrum of disease can present as a mild flulike illness, aseptic meningitis or severeencephalomyelitis. 60-75% of symptomatic patientspresent with encephalitis and 5-10% present withmeningitis. The case fatality rate is 20-30% and 50-60%of encephalitis survivors have neuropsychiatric sequelaeat discharge with a higher incidence of damage inchildren compared to adults.44
After inoculation into the skin the virus replicates inthe subcutaneous tissues, the lymphnodes and bloodstream before entering the brain. Previous infection dueto other flaviviruses like dengue may protect againstsevere disease due to the presence of protective cross-reacting antibodies.
Factors which govern severe illness include43

a.Failure to produce neutralizing antibodies

b.Genetic susceptibility to infection by flaviviruses

c.Advanced age-possibly due to a breakdown in theblood-brain barrier due to cerebrovascular disease

d.Neurocysticercosis : due to a breakdown in theblood-brain barrier due to inflammation

e.Virulent genotypes of the virus

Clinical manifestations : Patients with encephalitispresent with altered sensorium, seizures and abnormalposturing. Severe brainstem injury can cause a ‘locked-in’ state. Involvement of the basal ganglia can presentwith a parkinsonian syndrome, opisthotonus,choreoathetosis, myoclonic jerks and opsoclonusmyoclonus.43,45
Flaccid weakness with absent reflexes may occur in20-60% of patients with encephalitis. This may involvethe respiratory and bulbar musculature and occurs dueto direct invasion of the anterior horn cells, acute painfulretention of urine may be present.
Investigations : Nerve conduction studies showreduced or absent compound muscle action potentialswith preserved sensory action potentials and normalconduction velocities. EMG is consistent withdenervation. Sometimes demyelination may also occur.
Initial leucocytosis may be followed by leukopenia.CSF may show a pleocytosis. MRI is more sensitive thanCT for showing characteristic lesions involving thethalamus and basal ganglia.43,44 EEG may show ageneralized slowing.
Diagnosis is with an IgM capture ELISA or reversetranscriptase PCR of blood or CSF.42
There is no specific treatment available. Trials haveshown that interferon alfa or ribavirin are not useful.Seizures and raised ICP should be treated according tostandard protocols.43
This is a bacterial invasion of skeletal muscle usuallydue to Staphylococcus aureus.
Other bacteria like Strep pyogenes, Strep pneumoniae,H. influenzae, Gram-negative bacteria and anerobes canalso invade muscle, especially in immunocompromisedpatients.46
The pathogenesis involves the seeding of sites ofmuscle injury following transient bacteremia. PMNs andopsonins play an important role in defending againststaphylococcal infections and quantitative or qualitativedefects predispose to pyomyositis.46
Large skeletal muscles like the thigh, calf, gluteal andshoulder regions are typically involved.
The disease may have 3 stages with the first stagehaving muscle pain, swelling and low grade fever, thesecond stage occurs 1-2 weeks later with progressivesuppuration of the muscle which then may be followedby the third stage where there is bacteremia with possiblecomplications like septic shock, endocarditis,pneumonia, pericarditis, septic arthritis, brain abscessand rhabdomyolysis.47
Leucocytosis is often found, blood cultures may bepositive for staph and the serum CPK may be raised attimes to levels of 4000 U/L
Imaging with MRI or CT will often show abscessformation.46 These abscesses should be drained and thepus sent for SCABS.
Treatment involves use of antibiotics like cloxacillin1-2 g IV q 6h or cefazolin 2g IV q 8 h, addition ofclindamycin 600-900 mg IV q6-8h in mixed infectionand vancomycin in penicillin allergic patients.
Abscess drainage and debridement is essential in thesuppurative stage of the disease.

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