The employer and insurer appeal from the compensation judge’s awards of temporary total disability and medical benefits.  We affirm.

On July 25, 2005, Phyllis Christensen sustained a work-related injury to her right knee when she stepped on a craft bead and twisted the knee in the course of her work in the Housekeeping Department at Burns Manor Nursing Home.  Ms. Christensen [the employee] was fifty-seven years old on that date and was evidently earning a weekly wage of $386.67.  She had no history of any right knee problems prior to that date.  The employee sought medical attention for her injury for the first time on September 15, 2005, when she was diagnosed, by her family physician osteopath Dr. Dennis Murphy’s physician’s assistant Paul Coleman, with right knee pain probably secondary to a meniscal injury.  Burns Manor Nursing Home [the employer] and its insurer acknowledged liability for the injury and commenced payment of benefits.

After about two years of conservative treatment, by Dr. Murphy, PA Coleman, and eventually orthopedist Dr. Gordon Walker, proved ineffective, Dr. Walker recommended arthroscopic surgery, which he performed on April 9, 2007.  When that treatment also proved ineffective in relieving the employee’s pain, even with steroid injections, on September 11, 2007, Dr. Walker recommended a total right knee arthroplasty.  The procedure was planned for October 15, 2007, but was aborted when the employee became ill and vomited consequent to the anesthetic.  The employee subsequently contracted pneumonia from aspirating the discharge, and the arthroplasty was postponed until the following year, when it was performed by Dr. Walker on February 11, 2008.  By February 29, 2008, the employee was “doing quite well,” and there was no sign of infection.  By midsummer that year the employee was back at sedentary work full time, and by August she was released to begin working two hours per day at her regular nursing home activities.  About that same time, the employee began experiencing a “give-way” sensation in the knee, and some pain, warmth, and swelling began to set in, and in November and December of that year she underwent testing for infection.  Blood tests were essentially normal, but bone scans on December 3 and 18, 2008, showed mildly increased blood flow that was consistent with either normal post-surgery healing or the “more worrisome” possibility of low grade infection.

On January 15, 2009, the employee saw orthopedist Dr. Kyle Swanson, on referral from PA Coleman for an opinion as to revision of her total right knee arthrodesis.  On the basis of essentially normal seriological markers, Dr. Swanson concluded that the likelihood of infection was low, and he indicated that he thought that doing a total knee replacement revision would be a difficult and painful surgery, without guarantee of recovery with less pain.  On those conclusions, he prescribed a knee brace, recommended that the employee, who is 5’2” and weighs 225 pounds, try to improve her overall conditioning, and encouraged her to seek further medical opinion “until she feels comfortable” with her situation.  The employee saw Dr. Murphy on January 26, 2009, whom she informed that she thought she had an infected total knee and from whom she requested a prescription of antibiotics.  Dr. Murphy recommended that she follow up with a knee specialist for possible IV antibiotics instead of taking an oral antibiotic.

On March 6, 2009, the employee saw orthopedist Dr. Joseph Nessler, who repeated blood tests for infection and also aspirated fluid from the knee joint itself for testing, all tests in the end proving normal.  Examination revealed some laxity and instability in the knee, and x-rays of the knee revealed some lucency that was consistent with either a mechanical failure of bone cement or an indolent infection, although the latter appeared doubtful.  Having noted in the process also some significant loosening of the right knee ligaments, Dr. Nessler recommended a revision of the right knee arthroplasty to improve stability, scheduling a pre-operative physical exam and still anticipating the possible complication of an underlying infection.

On March 16, 2009, the employee reported to her QRC that she had slipped on some ice while walking in her driveway the day before, that she “started to do the splits,” her right leg going out to the side and behind her and her left hip ending up hurting.  By the following day, March 17, 2009, the employee was experiencing severe low back pain, and her husband took her to a Hutchinson area emergency room, where she was seen by osteopath Dr. James Mona.  Dr. Mona recorded a history of a fall at home on some ice that had resulted in tightness and spasm in the low back, which the employee was convinced was “more than a back strain.”  Upon examination, Dr. Mona diagnosed lumbosacral strain, prescribed medication, and released the employee to follow up with her family physician the following day.  Immediately upon returning home, the employee called Dr. Murphy and informed him of what had happened, explaining that she had injured herself when her knee buckled in the driveway two days earlier.  She requested from Dr. Murphy a prescription of OxyContin in place of her Percocet, which “wasn’t really helping,” and Dr. Murphy complied.

The employee was seen at the emergency room again two days later, on March 19, 2009, due to “[c]onfusion” and a “mental status change” deemed “most likely due to medication misuse.”  Her medications were evidently cut back to see if they were contributing to her confusion, but her confusion apparently only increased.  An IV was started, and she received two liters of saline, which apparently left her “a little bit more lucid.”  A CT scan of her head proved negative, but she was admitted to the hospital for further evaluation.  By March 20, 2009, the employee was complaining of severe and radiating low back pain, and straight leg raising was positive on the left, so she was restarted on OxyContin.  CT scans of the employee’s back on that date proved inconclusive, but on March 21, 2009, she continued to complain of lumbar and right knee pain and of extreme pain to palpation at the SI joints bilaterally.  On March 22, 2009, she reportedly had less pain in her back but more in her right knee, and she remained confused and hallucinatory.  On March 23, 2009, seeming “to hurt all over,” the employee was moved to the intensive care unit due to increased confusion, elevated heart rate, and agitation.  Her urine was found positive for methicillin-resistant staph aureus [MRSA], although not in a significant colony count, and she was transferred to Abbott Northwestern Hospital, where it was noted by Dr. Ashok Ojha that she was “apparently MRSA positive in the past.”  The employee’s radiological report indicated a history of “back pain and urinary tract infection,” and it was concluded that “[s]epsis appears to be the most likely working diagnosis.”

On March 24, 2009, the employee was examined by infectious disease consultant Dr. Daniel Anderson regarding her apparent MRSA infection.  Dr. Anderson discovered an infected abscess in the crease of the employee’s right elbow and assessed “aureus sepsis,” noting its source as “? R arm site recent venipuncture,” but he found it “[d]ifficult to say if [the infection was] present at time [of] admission to outside hospital or if acquired during that hospital stay.”  Dr. Anderson drained pus from the elbow-crease abscess, noting that he found no such abscess near the employee’s spine.  The following day, March 25, 2009, Dr. Anderson diagnosed “MRSA sepsis,” noting that a slight amount of pus had been drained from the venipuncture site again and that there was MRI evidence of a spinal epidural abscess and of a possible right knee prosthetic joint infection.

Recent aspiration of the employee’s right knee had revealed purulent material, and on March 26, 2009, the employee underwent surgery on the knee, performed by Dr. John Kearns, and infection was confirmed.  Given that the employee was known to host MRSA bacteria, and because an artificial joint like the employee’s right knee does not have a blood flow to effectively disseminate antibiotic medication, it was deemed necessary to remove the employee’s right knee prosthesis pending eradication of the infection.  On March 28, 2009, Dr. Thomas Davin summarized the employee’s recent history as follows:  “[She] presented with confusion and hallucinations.  She was found to have an MRSA bacteremia and metastatic infections including psoas and epidural ab[s]cesses.  Her knee prosthesis was considered a possible source and this has been removed.  Other potential sources include iv and blood drawing sites.”  Dr. Davin reported that “[i]t is suspected that the knee prosthesis may have been the culprit for her, i.e., the original infection.”  The employee was deemed “critically ill” at the time, with acute renal failure “likely due to her septicemia.”  Her diagnosis on March 29, 2009, was MRSA bacteremia, “with infected right total knee arthroplasty, now explanted, multifocal spinal epidural abscesses and left psoas muscle abscess.”  On March 30, 2009 Dr. Anderson noted that the “pink-ness” was nearly gone from the employee’s right arm, although there was “still yellowish at [the] site [of the] venipuncture,” and on April 2, 2009, there was still some drainage from the right elbow crease.  There remained concern also for neurological compromise due to the employee’s spinal infection, and on that same date, April 2, 2009, the employee underwent surgery on her back to drain abscesses at all levels of her spine.  On April 5, 2009, Dr. Neelay Kothari noted, “MRSA sepsis; original source unclear, has multiple sites of infection, including . . . ,” without listing the right elbow crease or its particular abscess among those sites.  By April 6, 2009, the employee’s acute renal failure had begun to improve, and on April 21, 2009, she was discharged from Abbott Northwestern Hospital and transferred to Regency Rehab Hospital.

On June 19, 2009, infectious disease specialist Dr. Gary Kravitz performed a review of the employee’s medical records at the request of the employer’s insurer.  In his assessment, Dr. Kravitz concluded that the employee developed bacteremia, which he defined as “blood stream infection,” due to MRSA “sometime between March 19, 2009 and March 23, 2009,” which “likely originated due to some minor injury in the left^[1] antecubital fossa” and “could have been at the site of a venipuncture or could have occurred due to some other innocuous injury to this area.”  Later in his report Dr. Kravitz asserts, without acknowledging a modification, that the onset of the infection was “sometime between March 17, 2009 and March 23, 2009” (underscoring added).  Dr. Kravitz noted that the employee was known to have “a history of prior colonization or infection with MRSA,” adding that “[u]p to 3% percent of the general populous is colonized with this organism.”  Dr. Kravitz explained that the most common tissues involved in an MRSA infection are the heart valves and the bones, others being kidney and urinary tract tissues and tissues surrounding the lower back.  Once an MRSA infection develops, he added, “the infection will often seed a total joint arthroplasty, such as a total knee or hip replacement, and lead to the acute onset of infection.”  He indicated that it appeared to him that the employee had the onset of her MRSA bacteremia while in the Hutchinson Hospital, as evidenced by “her progressive decline in mental status, her progressive rise in white count, the abrupt rise in white cells in the urine, . . . the precipitous drop in serum albumin that occurred between March 19 and March 23, and the positive blood and urine cultures for MRSA on March 23, 2009.”  Dr. Kravitz found noteworthy the fact that, from March 19 through March 25, 2009, no abnormality was identified in the right knee on physical examination and that tests on March 6, 2009, eleven days before the employee’s back injury, had ruled out the presence of any infection yet on that date.

On June 25, 2009, the insurer filed a notice of intention to discontinue the employee’s temporary total disability benefits, alleging that the employee’s July 25, 2005, work injury was not a substantial contributing factor in her current disability and need for treatment and that such benefits had earlier been paid based on a mistake of fact.  An administrative conference was held on August 11, 2009, subsequent to which, by an order filed August 19, 2009, the insurer’s request to discontinue benefits was denied.

In a letter to the employee’s attorney dated August 17, 2009, Dr. Murphy opined that the employee’s “right knee joint was the source of [the employee’s] MRSA, and therefore the cause of the [employee’s] significant health problems.”  “[B]ut for the fact that she had to have a right knee replacement from her work injury,” he went on, “she would not have gotten an MRSA infection sepsis like this.”  The doctor acknowledged, however, that he did “not have the knowledge or skill to determine how an infection could arise from a total knee operation, nor can I give an opinion about that.  I can only give an opinion about what the [employee’s] history and physical examination showed.”

On September 25, 2009, having apparently recovered from her infection, the employee underwent reimplantation of her right knee prosthesis by Dr. Kearns.  On October 16, 2009, the insurer filed a Petition to Discontinue the employee’s benefits, requesting a hearing on causation of the employee’s MRSA infection and a credit for benefits paid since March 16, 2009.  By October 29, 2009, the employee was reported to be doing well, with minimal knee pain, and continued exercise was ordered.  In a letter to the employee’s attorney dated November 1, 2009, Dr. Kearns agreed with Dr. Kravitz’s opinion that the likely source of the employee’s MRSA infection was “metastatic spread from one site to the other, as suggested by the abscess in the right antecubital fossa,” rather than any generation in the course of the employee’s total knee replacement in February 2008.  Dr. Kearns indicated that he considered the employee to be totally disabled from any work activities and in need of continued rehabilitation of both lower extremities, her left lower extremity now being of more concern than her right, due to a significant residual weakness that was rendering her unable to walk.

On December 10, 2009, Dr. Murphy testified by deposition, in part as follows regarding the cause of the employee’s MRSA infection:

On December 16, 2009, Dr. Kravitz testified by deposition, essentially reiterating opinions that he had asserted in his medical record review on June 19, 2009, except that he placed the onset of the employee’s infection “sometime after the 15th . . . and certainly it developed by the 22nd of March.”  He testified also in part that the loosening of the employee’s total knee that was evident on x-rays, which is a common cause of a painful prosthesis, can be due to a mechanical failure of the cement to hold or it can be due to an indolent infection in the joint.  Moreover, he testified, “total joints often act sort of like magnets for infection” when the infection gets into the bloodstream.  The fact that there did not appear to be any loosening in the employee’s joint when it was removed by Dr. Kearns suggested to Dr. Kravitz that the employee’s infection was an acute one, present for only a few days, rather than an indolent, chronic one.  Dr. Kravitz agreed that all of the employee’s treatment, including treatment for her spinal and paraspinal infections, had been reasonable and necessary.

The matter eventually came on for hearing on December 22, 2009.  Prior to hearing of the matter, the parties agreed to expand the issues to include disputed medical expenses related to the employee’s MRSA infection.  Issues at hearing were as follows:  (1) whether the employee’s July 2005 right knee work injury was a substantial contributing factor in the employee’s temporary total disability from March 16 to September 21, 2009;^[2] (2) whether that work injury was a substantial contributing factor in disputed medical expenses related to treatment of the employee’s MRSA infection; (3) whether treatment of that MRSA infection was necessary to cure and relieve the employee’s work injury; and (4) whether the employer and insurer were entitled to a credit for overpayment of temporary total disability benefits from March 16, 2009, to September 21, 2009.  At hearing, the employer and insurer stipulated in part that the disputed medical treatment was reasonable and necessary and that they would pay for such treatment if the compensation judge were to find that the work injury was a substantial contributing factor in the development of the MRSA infection.  Evidence admitted at hearing included a claim by intervenor Abbot Northwestern Hospital for reimbursement of $455,623.02 for expenses of the employee’s medical treatment between April 21, 2009, and September 25, 2009.  The record in the matter closed on December 22, 2009, at the conclusion of the hearing.^[3]

By findings and order filed March 1, 2010, the compensation judge concluded in part that the employee’s right knee work injury was a substantial contributing factor in the employee’s temporary total disability from March 16 to September 21, 2009, and in her need for the medical treatment for her MRSA infection, adding that “[t]reatment for the infection was necessary to cure or relieve the admitted right knee injury.”  In his memorandum, the judge explained further that, “[b]ecause the right knee condition was a substantial contributing factor in [the employee’s] injury on March 15, 2009, all of the blood testing after that date was related to the work injury.”  On those conclusions, the compensation judge ordered payment of the benefits at issue.  The employer and insurer appeal.

In reviewing cases on appeal, the Workers’ Compensation Court of Appeals must determine whether “the findings of fact and order [are] clearly erroneous and unsupported by substantial evidence in view of the entire record as submitted.”  Minn. Stat. § 176.421, subd. 1.  Substantial evidence supports the findings if, in the context of the entire record, “they are supported by evidence that a reasonable mind might accept as adequate.”  Hengemuhle v. Long Prairie Jaycees, 358 N.W.2d 54, 59, 37 W.C.D. 235, 239 (Minn. 1984).  Where evidence conflicts or more than one inference may reasonably be drawn from the evidence, the findings are to be affirmed.  Id. at 60, 37 W.C.D. at 240.  Similarly, “[f]actfindings are clearly erroneous only if the reviewing court on the entire evidence is left with a definite and firm conviction that a mistake has been committed.”  Northern States Power Co. v. Lyion Foods Prods., Inc., 304 Minn. 196, 201, 229 N.W.2d 521, 524 (1975).  Findings of fact should not be disturbed, even though the reviewing court might disagree with them, “unless they are clearly erroneous in the sense that they are manifestly contrary to the weight of the evidence or not reasonably supported by the evidence as a whole.”  Id.

At Finding 6, the compensation judge concluded that the employee’s work-injured right knee condition was a substantial contributing factor in the employee’s March 15, 2009, fall in her driveway that precipitated her March 19, 2009, hospitalization.  In his memorandum, the judge explained that, because the work injury was a substantial factor in that March 15, 2009, incident, “all of the blood testing after that date was related to the work injury.”  Pursuant to this conclusion, the judge found at Finding 29 that the employee’s right knee work injury was a substantial contributing factor in the employee’s disputed temporary total disability from March 16 to September 21, 2009, and in the employee’s need for disputed medical treatment related to her MRSA infection, explaining that “[t]reatment for the infection was necessary to cure or relieve the admitted right knee injury.”

The employer and insurer contend that these conclusions of the judge are clearly erroneous, first in that they disregard unopposed medical opinion of Dr. Kravitz.  They argue that Dr. Kravitz opined in his report of June 19, 2009, that the employee did not have a chronic MRSA infection in her right knee joint following her total knee replacement and that Dr. Murphy’s opinion to the contrary on August 17, 2009, does not constitute viable medical opposition, in that Dr. Murphy openly acknowledged that he did not have “the knowledge or skill” to render an opinion on the topic, other than on the basis of “what the [employee’s] history and physical examination showed.”  They note further that Dr. Kravitz initially opined that the infection was instead a skin infection that did not enter the employee’s blood stream until some time between March 19 and March 23, 2009, noting also that he later modified that opinion based on additional information, to opine that the infection actually started sometime between March 15 and March 22, 2009.  The employer and insurer argue that the employee was an MRSA carrier and that she already had symptoms of the infection at the time she entered the Hutchinson hospital on March 19, 2009.  The employer and insurer contend further that, once “it was established by a preponderance of the evidence that the employee did not have an indolent (chronic) infection,” as confirmed by the judge’s own conclusion at the beginning of his memorandum, the judge erred by not shifting the burden of proof onto the employee to show more affirmatively that the MRSA infection was causally related to her knee injury.

On these arguments, the employer and insurer contend that Finding 29 should be reversed in all respects and that the employer and insurer should be awarded a credit for temporary total disability benefits paid from March 16, 2009, to September 21, 2009.  In the alternative, they request that Finding 29 be vacated and the case be remanded to the compensation judge for additional findings as to whether the employee was subject to an MRSA infection prior to her hospitalization on March 19, 2009, and whether the employer and insurer are responsible for treatment to body parts other than the employee’s right knee, to which the infection merely spread - - including the employee’s back and psoas muscle.  We are not persuaded.

There was an issue at hearing as to whether the employee’s work-related right knee condition substantially contributed to her fall in her driveway on March 15, 2009, and the employer and insurer have nominally appealed from the compensation judge’s conclusion in Finding 6 that it did so contribute.  They have not briefed that issue on appeal, however, and therefore we will not address it.  See Minn. R. 9800.0900, subp. 1 (“Issues raised in the notice of appeal but not addressed in the brief shall be deemed waived and will not be decided by the court.”).  The issues remaining before us are very complex ones of medical causation, ones in which experts in the field not only disagree with each other but often appear far less than certain of even their own conclusions.  We conclude that the compensation judge’s decision was very reasonable in light of the complexity of the medical history and record and the nature of the medical opinion in evidence.

Having concluded at Finding 6, uncontested now on appeal, that the employee’s work-injured right knee was a substantial factor in her fall in her driveway on March 15, 2009, that precipitated her emergency room treatment on March 17, 2009, and her hospitalization on March 19, 2009, the compensation judge concluded at Finding 29 that the work injury was a substantial contributing factor in the employee’s temporary total disability from March 16 to September 21, 2009, and in medical expenses related to the MRSA infection for which she was subsequently treated, explaining in his memorandum that “all of the blood testing after [March 15, 2009, therefore] was related to the work injury.”  The judge had indicated expressly at the beginning of that memorandum his conclusion that the employee’s infection was probably not indolent since her original total knee replacement.  He then went on to explain, referencing causation assessments of both Dr. Anderson and Dr. Kravitz relating the employee’s infection at least possibly if not probably to an elbow crease or venipuncture site, that, “[b]ased on the entire record, this court is persuaded that [a venipuncture site] was the original source of the infection.”  Given the reports and expressed opinions of Drs. Anderson and Kravitz, as recounted above, this conclusion by the judge was not unreasonable and did not imply an inappropriately light burden of proof for the employee in these circumstances.

The employee was initially hospitalized for back pain consequent to a fall attributable at least in part to her right knee work injury, pursuant to the compensation judge’s conclusion in Finding 6, uncontested in the employer and insurer’s brief.  Once hospitalized, she became fairly suddenly and seriously symptomatic with an MRSA infection, which Dr. Anderson supposed on March 24, 2009, may have originated near her right elbow crease.  This supposition is given credence by more than one reference to Dr. Anderson’s drawing pus from a venipuncture site on the employee’s right arm and by the fact that Dr. Davin, on March 28, 2009,  notes that “potential sources [of the infection] include iv and blood drawing sites.”  Moreover, Dr. Anderson repeatedly refers to a puncture at the right elbow crease, and there is no evidence of injury to that area other than what occurred in the hospital.

Dr. Kravitz ultimately disputes the likelihood that a person can develop an infection at a blood drawing site, testifying on December 16, 2009, “I think [the employee] was colonized with MRSA, but she developed what we call invasive infection.  It caused an invasive infection in her right arm, and that this led to the bloodstream infection, which then involved multiple sites inside of her body.”  He had suggested earlier, however, in his report on June 19, 2009, that the employee’s initial infection “could have been at the site of a venipuncture,” and he acknowledged in his deposition that Dr. Anderson had “immediately noted that there was an abscess in the right elbow crease,” which Dr. Kravitz acknowledged to be a primary site of the employee’s infection.  Dr. Kravitz testified that the most characteristic hallmark of a staph infection, particularly of an MRSA infection, is a cutaneous abscess, which he indicated is generally considered the source of the infection.  And Dr. Kravitz himself testified that “MRSA is something people will frequently pick up in the hospital.  So usually when people have MRSA, we look to see if there’s something that happened in the hospital.”

As the compensation judge noted, records in evidence do not clearly indicate the arm from which the employee’s blood was drawn or in which arm her IVs were installed while she was in the hospital.  Drs. Anderson and Davin and even Dr. Kravitz refer to an abscess at the employee’s right elbow crease, from which they conclude with varying certainty that that location was probably the source of the employee’s infection.  Nor is there any clear evidence that the employee had an infection prior to her hospitalization.  Because MRSA infections are not uncommon to hospital stays, because the employee’s examining physicians as a group seem to identify her right elbow crease as the likely source of her infection, and because the employee clearly developed symptoms of her infection about the time of her March 19, 2009, hospitalization, it was not unreasonable for the compensation judge to conclude that the infection was consequent to her hospitalization, which in turn was consequent to her fall on March 15, which in turn was consequent in part to the condition of her work-injured right knee.

With regard to the employer and insurer’s argument that the employee did not have a chronic MRSA infection in her knee following her original knee replacement, we need only reiterate the judge’s own conclusion to this effect at the beginning of his memorandum, as referenced above.  With regard to their contention that the employee already had the infection at the time she entered the hospital on March 19, 2009, we would note that Dr. Kravitz’s opinion on June 19, 2009, was that the infection was probably contracted on or after that date, and even his slightly modified opinion in his December 16, 2009, deposition--that the infection began between March 15 and March 22, 2009--was permissive of an onset after the employee’s March 19, 2009, hospitalization.  We conclude that the compensation judge’s decision was reasonable and legally proper under this very complex set of facts, and therefore we affirm it in its entirety.  See Hengemuhle, 358 N.W.2d at 59, 37 W.C.D. at 239.